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Biochemistry, Genetics and Molecular Biology » "Oxidative Stress and Chronic Degenerative Diseases - A Role for Antioxidants", book edited by José A. Morales-González, ISBN 978-953-51-1123-8, Published: May 22, 2013 under CC BY 3.0 license. © The Author(s).

Chapter 16

The Role of Natural Antioxidants in Cancer Disease

By Carmen Valadez-Vega, Luis Delgado-Olivares, José A. Morales González, Ernesto Alanís García, José Roberto Villagomez Ibarra, Esther Ramírez Moreno , Manuel Sánchez Gutiérrez, María Teresa Sumaya Martínez, Zuñiga Pérez Clara and Zuli Calderón Ramos
DOI: 10.5772/51503

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The Role of Natural Antioxidants in Cancer Disease

Carmen Valadez-Vega1, Luis Delgado-Olivares1, José A. Morales González1, Ernesto Alanís García1, José Roberto Villagomez Ibarra2, Esther Ramírez Moreno 1, Manuel Sánchez Gutiérrez1, María Teresa Sumaya Martínez3, Zuñiga Pérez Clara1 and Zuli Calderón Ramos1

1. Introduction

Cell oxidation can lead to the onset and development of a wide range of diseases including Alzheimer and Parkinson, the pathologies caused by diabetes, rheumatoid arthritis, neurodegeneration in motor neuron diseases, and cancer. Reactive species (RS) of various types are powerful oxidizing agents, capable of damaging DNA and other biomolecules. Increased formation of RS can promote the development of malignancy, ‘normal’ rates of RS generation may account for the increased risk of cancer development.

Oxidants and free radicals are inevitably produced during the majority of physiological and metabolic processes and the human body has defensive antioxidant mechanisms; these mechanisms vary according to cell and tissue type and may act antagonistically or synergistically. They include natural enzymes like Superoxide dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GPx), as well as antioxidants such as vitamins, carotenoids, polyphenols, and other natural antioxidants, which have attracted great interest in recent years.

There has been a great deal of interest of late in the role of complementary and alternative drugs for the treatment of various acute and chronic diseases. Among the several classes of phytochemicals, interest has focused on the anti-inflammatory and antioxidant properties of the polyphenols that are found in various botanical agents. Plant vegetables and spices used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discoveries and development.

Recently, researches on medicinal plants has drawn global attention; large bodies of evidence have accumulated to demonstrate the promising potential of medicinal plants used in various traditional, complementary, and alternate treatment systems of human diseases. The plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, flavonoids, etc., which have been screened in vivo and in vitro and have indicated antioxidant and anticarcinogenic properties and which are used to developed drugs or dietary supplements.

Evidence suggests that the plant kingdom is considered a good candidate for chemoprevention and cancer therapy due to the high concentration and wide variety of antioxidants such as resveratrol, genestein, beicalein, vitamin A, vitamin C, polyphenols, (‒)‒Epigallocatechin 3-gallate, flavonoids, polyphenols, gallic acid, glycosides, verbascoside, calceorioside, epicatechin, quercetin, curcumin, lovastatin, and many other types of compounds with the capability to inhibit the cell proliferation of different cancer cells in vitro and in vitro, such as colon cancer (HT-29, SW48, HCT116), breast (MCF7, MDA), cervix (HeLa, SiHa, Ca-Ski, C33-A), liver (Hep G2), skin (A 431), fibroblasts (3T3 SV40), and many other malignant cells; studies have indicated that antioxidants can be employed efficiently as chemopreventives and as effective inhibitors of cell proliferation, promoting cell apoptosis, and increasing detoxification enzymes, and inhibiting gene expression and scavenger Reactive oxygen species (ROS). Thus, many researchers are working with different types of natural antioxidants with the aim of finding those with the greatest capacity to inhibit the development of cancer both in vitro as well as in vivo, because these compounds have exhibited high potential for use not only in the treatment of this disease, but they also act as good chemoprotective agents.

2. Antioxidants

The production of ROS during metabolism is an inevitable phenomenon associated with the process of aerobic metabolism; on the other hand, we are exposed at all times to several exogenous sources of oxidant molecules, for example, environmental and pollutant factors and many dietary compounds, which increase their levels. ROS participate in different cellular processes; their intracellular levels are relatively low. However, because ROS are highly toxic when their concentration increases, the phenomenon denominated Oxidative stress (OS) is produced [123], which can injure various cellular biomolecules, causing serious damage to tissues and organs and resulting in chronic diseases [24]. Oxidative damage can be prevented by antioxidants, which are present within the cell at low concentrations compared with oxidant molecules [141, 50].

Antioxidants are capable of donating electrons to stabilize ROS and to inhibit their detrimental effects, including both endogenous (synthesized by the body itself) and exogenous molecules (those from external sources to the body) [141]. Endogenous antioxidants include Superoxide dismutase (SOD), which catalyzes the dismutation reaction of superoxide (O2•) into hydrogen peroxide (H2O2), which is in turn transformed into oxygen and water for the Catalase (CT), and in addition Glutathione peroxidase (GPx) can catalyze its reduction; however, if in the presence of transition metals such as iron, H2O2, by means of the Fenton reaction, can produce the hydroxyl radical (OH•); wich is of more reactive the ROS, capable to produce the majority of oxidative damage [24]. On the other hand, exogenous antioxidants can be from animal and plant sources; however, those of plant origin are of great interest because they can contain major antioxidant activity [19]. Different reports show that persons with a high intake of a diet rich in fruit and vegetables have an important risk reduction of developing cancer, mainly due to their antioxidant content [70]. Among the vegetable antioxidants are vitamins E and C, and ß-carotene, which are associated with diminished cardiovascular disease and a decreased risk of any cancer [48]. In particular, ß-carotene and vitamin E can reduce the risk of breast cancer, vitamin C, ß-carotene, and lutein/zeaxanthin possess a protector effect against ovarian cancer, and vitamin C, ß-carotene, and rivoflavin prevent colorectal cancer [70], while flavonoids such as plant phenolics and wine phenolics can inhibit lipid peroxidation and lipoxygenase enzymes. In addition, any microelement, such as Se, Zn, Mn, and Cu, can exhibit antioxidant activity [48, 24].

In recent years, interest has grown in the use of natural antioxidants for the prevention or treatment of different diseases related with OS; however despite the widespread information of the beneficial effects of antioxidants in the prevention of cancer, their use remains questionable, because different reports have shown that reducing the levels of ROS may have counterproductive effects because due to raising the risk of cancer; the latter may be due to that ROS can produce apoptosis in malignant cells [38, 101].

3. Molecular Studies of Natural Antioxidants

Different types of natural antioxidants are present in fruit and vegetables; they have synergistic interactions that are important due to their activity and regenerative potential. For example, ascorbate can regenerate into α-tocopherol [53], and the ascorbate radical is regenerated into other antioxidants via the thiol redox cycle. Taken together, all of these interactions are known as the “antioxidant network”.

Vitamin E is an antioxidant that penetrates rapidly through the skin and is incorporated into the cellular membranes, inhibiting lipid peroxidation; specifically, α-tocotrienol, the vitamin E isoform, demonstrates greatest protection. Additionally, vitamin E possesses antiproliferative properties that interfere in signal transduction and in inducing cell cycle arrest.

Tumor necrosis factor-alpha (TNF-α) is a cytokine that, under normal conditions, induces inflammation, tumor inhibition, and apoptotic cell death. However, when the former undergoes deregulation, it acts as a breast tumor promoter, enhancing the proliferation of chemically induced mammary tumors [113]. Phenolic antioxidants can block the increase of TNF-α at the transcriptional level in the nucleus, which suggests the molecular mechanism of phenolic antioxidants through control of cytokine induction [81].

4. Oxidative Stress and Diseases

The ROS, as the superoxide anion (O2), hydrogen peroxide (H2O2), and the hydroxyl radical (OH•), are produced during cell metabolism in the lysosomes, peroxisomes, endoplasmic reticulum in the process carried out to obtain energy such as Adenosine triphosphate (ATP) [108]. There are other sources of oxidant molecules, such as pollution, the environment, and certain foods. During recent years, it has been discovered that during aging, the mitochondria increase the levels of ROS production and antioxidant endogens are diminished [98, 13]. ROS play an important role in the physiological process; however, due to their toxicity, their levels must be controlled by the endogenous antioxidant system. But when ROS formation is increased, an imbalance is promoted between these and the antioxidant molecules; phenomenon known as Oxidative stress (OS) [123]. OS can cause oxidative damage of proteins, lipids, and nucleic acids, macromolecules involved in the cell function, membrane integrity, or in maintaining genetic information (nucleic acids) [44, 45, 65].

Proteins are responsible for different cell processes (enzymatic, hormonal, structural support). The oxidation of proteins produces disulfide crosslinks, nitration, or tyrosine residues, and carbonylation, resulting in the loss of the structure and function of proteins and fragmentation [11, 97]. But because the chaperones are susceptible to oxidative damage, allowing the accumulation of misfolding proteins and increasing their susceptibility to protease degradation [115], however, the proteasome also undergoes oxidation and its activity is diminished, which makes the aggregates accumulate in the cell wich have been associated with aging and various pathologies, such as cancer and neurodegenerative disorders, such as Parkinson, Huntington, and Alzheimer disease [98].

The brain is the organ with the highest oxygen consumption; it has high levels of fatty acids, iron, and low antioxidant defenses. This is an organ with major susceptibility to oxidative damage [141], producing neurodegeneration that results in different diseases such as Parkinson disease, Alzheimer disease, Down syndrome, autism, bipolar disorder, and epilepsy [23, 24], and the cognitive alteration known as Mild cognitive impairment (MCI), which is produced preferentially in regions of the brain involved in regulating cognition, contributing to the development of dementia [65]. Similar processes occur during aging, resulting in the genetic response of increasing levels of antioxidant enzymes and chaperone proteins [73]. Reduction of OS causes improvement of the long-term memory [102].

Polyunsaturated fatty acids (mainly compounds of the membranes) are susceptible to peroxidation, which affects the integrity of the membranes of organelles of the cell membrane and the respiratory chain, in turn affecting cell viability. Lipid peroxidation produces aldehydes such as 4-hydroxy-2 E-nonenal, which is toxic and is involved in alterations in Alzheimer disease and DNA damage, causing mutations associated with the development of cancer [38, 20].

Ribosomal RNA and transfer RNA constitute the majority of stable species of cellular RNA, which possess a greater oxidation rate than DNA. The major modification for oxidation into RNA comprises 8-hydroxyGuanine (8-oxoG), which under normal conditions is present three times more in non-ribosomal that in ribosomal RNA; however, when the cell is exposed to H2O2, the concentration of 8-oxoG in ribosomal RNA increases at the same levels in both RNA [97]. RNA oxidation can diminish the capacity of replacement oxidation of proteins [65, 44] and the inhibition of protein synthesis, cell cycle arrest, and cell death. Oxidation of RNA is involved in the development of cancer, viral infections, AIDS, hepatitis (VIH-1; HCV; 107, 148], and neurological diseases. It has been reported that each neurological disease, present a damage oxidative of RNA in a specific region on the brain, for example in Alzheimer disease, there are increased RNA oxidation in the hippocampus and cerebral neocortex, while in Parkinson disease, RNA oxidation is localized in the sustancia nigra [97].

On the other hand, high-fat diets induce obesity and insulin resistance, resulting in increased ROS production, which modifies sympathetic brain activity, which in turn contributes to the rise in blood pressure, increase in insulin resistance, and obesity [6]. Obesity is the principal factor in the development of the metabolic syndrome, due to that persons with obesity have deficient antioxidant defense and increased production of ROS [126, 30, 75], which leads to spoilage and subsequently cell death, resulting in tissue and organ damage, to tissues causing serious health problems such as insulin resistance [7], diabetes mellitus, and hypertension [82]. Moreover, in the metabolic syndrome, NAD(P)H oxidase, the major source of ROS in several tissues, is up-regulated, resulting in an increase of ROS production and the down-regulation of several antioxidant enzymes (SOD isoforms, GPx, and heme oxygenase) [114]. This enzyme, specifically in the type 4 isoform (NOX4), is implicated in the damage due to OS during cerebral ischemia [67].

The scientific literature has shown that oxidative stress is involved in the development of a wide range of disease, such as heart diseases, Hutchinson-Gilford syndrome or progeria, hypertensive brain injury, muscular dystrophy, multiple sclerosis, congenital cataract, retinal degeneration, retinopathy of the premature, autoimmune diseases, cardiovascular abnormalities, nephrological disorders, emphysema, stroke, rheumatoid arthritis, anemia, hepatitis, pancreatitis, aging, premature wrinkles and dry skin, endothelial dysfunction, and dermatitis, among others [83, 7, 137, 91, 23, ¸102].

However the most important damage caused by OS are the DNA modifications, which can result in permanent mutations, due to that oxidative damage also affects the proteins involved in repairing the harm or reducing the OS (the endogenous antioxidant); thus, oxidative damage to DNA can be the cause of the development of various diseases, such as cancer [13, 51].

5. Cancer

Cancer is unnatural cell growth, in which cells can lose their natural function and spread throughout the blood in the entire body. Breast cancer is the most commonly diagnosed cancer in industrialized countries and has the highest death toll [88]. OS is involved in the process of the development of cancer and tumors, due to that ROS can damage the macromolecules as lipids, which react with metals (such as free iron and copper) and produce aldehydes and synthesize malondialdehyde-inducing mutations [96] or cause breaks in the double chain, produce modifications in guanine and thymine bases, and sister chromatid exchanges [16], which can affect the activities of signal transduction, transcription factors, and gene tumor suppressors such as p53, which is a gene important in apoptosis and in cell cycle control. This inactivation can increase the expression of proto-oncogenes [96] which can produce major damage. Oxidative damage or genetic defects that result in some defective enzymes are incapable of repairing the mutations increase the incidence of age-dependent cancer [51].

On the other hand, treatments with anticancer drugs and radiation increase ROS and decrease antioxidants content, producing a state of severe oxidative stress and causing apoptosis, resulting in side effects [96], while persistent oxidative stress at sublethal levels can result in resistance to apoptosis [16].

Some microorganisms, as bacteria and viruses, are involved, via OS, in the process of the production of certain cancers such as, for example Helicobacter pylori, inducing gastric cancer and colon cancer through the production of SO• [96]. It has been proposed that lower antioxidant activity increases the risk of developing cancer; thus, ingestion of antioxidants can prevent cancerogenesis. However is not clear the decrease of antioxidants levels is not clear, in as much as in freshly cancerous tissue, MnSOD levels are elevated; therefore, some investigators have proposed that this antioxidant enzyme is involved in tumor invasion; thus, it is possible that antioxidants have a role as pro-oxidants. Another point to consider is that when the 8-oxodG level in DNA increases, cancer rates do not increase [96, 51]. However, OS is a factor for cancer and other diseases, but not the sole factor for diseases, because others, such as genetic factors (genetic predisposition) are involved.

6. Antioxidants and Cancer

Humans are constantly bombarded by exogenous factors such as Ultraviolet (UV) rays, tobacco smoke, and many others agents that cause OS. Such stress can also arise from the drugs that are employed in medical practice. On the other hand, under physiological conditions, normal aerobic metabolism gives rise to active and potentially dangerous oxidants in cells and tissues; these endogenous sources of OS include those derived from the activities of mitochondria or microsomes and peroxisomes in the electron transfer system and from the activities of the NADPH enzyme present in macrophages and neutrophils as a mechanism of protection against infection. Various reducing substances in the human body control the status of oxidation-reduction (redox), and a continuing imbalance in favor of oxidation causes several problems when it exceeds the capacity of such a control [96].

Otto Warburg was the first scientist to implicate oxygen in cancer [147] as far back as the 1920s. However, the underlying mechanism by which oxygen might contribute to the carcinogenic process was undetermined for many years. The discovery of superoxide dismutase in 1968 by [90] led to an explosion of research on the role of reactive oxygen in the pathologies of biological organisms. Reactive oxygen has been specifically connected with not only cancer, but also many other human diseases [5, 57]. For many years, research on OS focused primarily on determining how ROS damage cells through indiscriminate reactions with the macromolecular machinery of a cell, particularly lipids, proteins, and DNA. It is well known and in great detail the manner in which ROS react with lipids, leading to the peroxidation of biological membranes and resulting in necrotic lesions [43] and the way ROS react with the nucleotides of DNA, leading to potential mutations [17, 43, 139].

When produced in excess, ROS (some of which are free radicals) can seriously alter the structure of biological substrates such as proteins, lipids, lipoproteins, and Deoxyribonucleic acid (DNA). They possess a huge range of potential actions on cells, and one could easily envisage them as anti-cancer (e.g., by promoting cell-cycle stasis, senescence, apoptosis, necrosis or other types of cell death, and inhibiting angiogenesis), or as pro-cancer (promoting proliferation, invasiveness, angiogenesis, metastasis, and suppressing apoptosis).

Active oxygen may be involved in carcinogenesis through two possible mechanisms: induction of gene mutations that result from cell injury [34], and the effects on signal transduction and transcription factors. Which mechanism it follows depends on factors such as the type of active oxygen species involved and the intensity of stress [86]. Cellular targets affected by oxidative stress include DNA, phospholipids, proteins, and carbohydrates on the cell membrane. Oxidized and injured DNA has the potential to induce genetic mutation. That some telomere genes are highly susceptible to mutation in the presence of free radicals is now apparent, and it is known that tumor suppressor genes such as p53 and cell cycle-related genes may undergo DNA damage. In addition, oxidized lipids react with metals to produce active substances (e.g., epoxides and aldehydes) or synthesize malondialdehyde, which has the potential to induce mutation. Active oxygen species act directly or indirectly via DNA damage on gene expression (DNA binding of transcription factors) and signaling at the cellular level.

Markers for OS can be divided into three categories:

  1. formation of modified molecules by free radical reactions;

  2. consumption or induction of antioxidant molecules or enzymes, and

  3. activation or inhibition of transcription factors.

Targets of free radicals include all types of molecules in the body. Among these, lipids, nucleic acids, and proteins are the major targets. Because free radicals are usually generated near membranes (cytoplasmic membrane, mitochondria, or endoplasmic reticulum), lipid peroxidation is the first reaction to occur. Lipid peroxidation products can be detected as classical Thiobarbituric acid (TBA)-reactive substances. Recently, the detection of 4-Hydroxy-2-nonenal (HNE) or Malondialdehyde (MDA) is favored due to their high specificity [32], aldehydes are end-products of lipid peroxidation but continue to be reactive with cell proteins [136].

Exposure to free radicals from a variety of sources has led organisms to develop a series of defense mechanisms that involve the following:

  1. preventative mechanisms;

  2. repair mechanisms;

  3. physical defenses, and

  4. antioxidant defenses.

Enzymatic antioxidant defenses include Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and Catalase (CAT). Non-enzymatic antioxidants are represented by ascorbic acid (vitamin C), α-tocopherol (vitamin E), Glutathione (GSH), carotenoids, flavonoids, tannins, triterpepenoids, saponins, glycosides, steroids, and other antioxidants [46]. Under normal conditions, there is a balance between both the activities and the intracellular levels of these antioxidants: this equilibrium is essential for the survival of organisms and their health

7. Antioxidants in Cancer Assays

Humans have evolved with antioxidant systems for protection against free radicals and ROS. These systems include some antioxidants produced in the body (endogenous) and others obtained from the diet (exogenous) [21]. The former include

  1. enzymatic defenses, such as Se-glutathione peroxidase, catalase, and superoxide dismutase, which metabolize superoxide, hydrogen peroxide, and lipid peroxides, thus preventing the majority of the formation of toxic HO∙, and

  2. non-enzymatic defenses, such as glutathione, histidine peptides, the iron-binding transfer proteins and ferritin, and dihydrolipoic acid, reduced Coenzyme Q10, melatonin, urate, and plasma protein thiols, with the latter two accounting for the major contribution to the radical-trapping capacity of plasma.

The various defenses are complementary to each other because they act against different species in different cellular compartments. However, despite these defense antioxidants (able either to suppress free radical formation and chain initiation or to scavenge free radicals and chain propagation), some ROS escape to cause damage. Thus, the body’s antioxidant system is also provided with repair antioxidants (able to repair damage) and based on proteases, lipases, transferases, and DNA repair enzymes [145, 103].

Owing to the incomplete efficiency of our endogenous defense systems and the existence of some physiopathological situations (cigarette smoke, air pollutants, UV radiation, a high, polyunsaturated fatty acid diet, inflammation, ischemia/reperfusion, etc.) in which ROS are produced in excess and at the wrong time and place, dietary antioxidants are required to diminish the cumulative effects of oxidative damage throughout the human lifespan [149, 47). Well known natural antioxidants derived from the diet, such as vitamins C, E, and A and the carotenoids, have been studied intensively [124]. In addition to these, antioxidants in plants might account for at least part of the health benefits associated with vegetable and fruit consumption [103].

The plants, vegetables, and spices used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discovery and development [85, 29].

Some reports indicate that the prevalence of use of complementary and alternative medicine by patients with cancer has been estimated at a range of 7‒64% [3, 4, 58]. At present, many patients with cancer combine some forms of complementary and alternative therapy with their conventional therapies [4, 58]. A recent survey of patients at a comprehensive cancer center placed the use of vitamin and minerals at 62.6%; of these patients, 76.6% combined the use of vitamins and minerals with conventional chemotherapy [58, 27].

These types of patients employ complementary and alternative therapies for a variety of reasons [31, 14]: to improve quality of life (77%); to improve immune function (71%); to prolong life (62%), or to relieve symptoms (44%) related with their disease [31]. Only 37.5% of the patients surveyed expected complementary and alternative therapies to cure their disease. Whatever the reasons, alternative therapy use is on the rise and this includes the use of megavitamins, minerals, and cocktails of natural substances during chemotherapy administration; these cocktails include antioxidants such as the commonly consumed antioxidants vitamin E (mixed tocopherols and tocotrienols), vitamin C, β-carotene (natural mixed carotenoids), polyphenols, tannins, terpenoids, alkaloids, flavonoids, vitamin A, and many others. Controversy exists concerning the use of antioxidants with chemotherapy, but increasing evidence suggests a benefit when antioxidants are added to chemotherapy [111, 112, 106, 151, 117, 105, 22, 27].

It is widely accepted that diets rich in fruits and plants are rich sources of different types of antioxidants; phenolic compounds are the most studied of these and have been recognized to possess a wide range of properties including antioxidant, antibacterial, anti-inflammatory, hepatoprotective, and anticarcinogenic actions [3, 4, 63]. Many of the biological functions of flavonoid, phenolic, catechin, curcumin, resveratrol, and genistein compounds have been attributed to their free-radical scavenging, metal-ion chelating, and antioxidant activities [118, 152]. Antioxidant phenolic agents have been implicated in the mechanisms of chemoprevention, which refers to the use of chemical substances of natural or of synthetic origin to reverse, retard, or delay the multistage carcinogenic process [29].

It has been shown that dietary phytochemicals can interfere with each stage of the development of carcinogenesis [130, 93]. As in the case of direct antioxidant effects, dietary polyphenols are most likely to exert their chemopreventive effects on the gastrointestinal tract, where they are present at highest concentrations [52, 49, 84, 75]. Indeed, studies have shown that various polyphenol-rich fruits and vegetables are particularly effective in protecting against several types of cancer development [84, 75, 59]. Dietary polyphenols may exert their anticancer effects through several possible mechanisms, such as removal of carcinogenic agents, modulation of cancer cell signaling and antioxidant enzymatic activities, and induction of apoptosis as well as of cell cycle arrest. Some of these effects may be related, at least partly, with their antioxidant activities [59]. They may exert protective effects against cancer development, particularly in the gastrointestinal tract, where they will be at their highest concentration. In fact, many studies have shown that various polyphenol-rich fruits and vegetables are particularly effective in protecting against colon cancer development [84, 75].

At the cellular level, there is good evidence that polyphenols present in tea, red wine, cocoa, fruit juices, and olive oil; at some level, they are able to stimulate carcinogenesis and tumor development [93]. For example, they may interact with reactive intermediates [28] and activated carcinogens and mutagens [18], they may modulate the activity of the key proteins involved in controlling cell cycle progression [104], and they may influence the expression of many cancer-associated genes [142]. Perhaps most notably, the anticancer properties of green tea flavanols have been reported in animal models and in human cell lines ( Takada et al., 2002], as well as in human intervention studies [60]. On the other hand, green tea consumption has been proposed as significantly reducing the risk of cancer of the biliary tract [133], bladder [110], breast [74], and colon [72]. Many of the anti-cancer properties associated with green tea are thought to be mediated by the flavanol Epigallocatechin gallate (EGCG), which has been shown to induce apoptosis and inhibit cancer cell growth by altering the expression of cell cycle regulatory proteins and the activity of signaling proteins involved in cell proliferation, transformation, and metastasis [66]. In addition to flavonoids, phenolic alcohols, lignans, and secoiridoids (all found at high concentrations in olive oil) are also thought to induce anti-carcinogenic effects [99] and have been reported in large intestinal cancer cell models [79], in animals [10, 128], and in humans [99]. These effects may be mediated by the ability of olive oil phenolics to inhibit initiation, promotion, and metastasis in human colon adenocarcinoma cells [42, 55] and to down-regulate the expression of COX-2 and Bcl-2 proteins, which play a crucial role in colorectal carcinogenesis [79, 146].

In vivo studies have demonstrated that many natural compounds found in plants and fruits have the capability to inhibit many types of human and animal cancer. Vitamins such as C, E, and A have shown that they can diminish cervical, bladder, prostate, intestinal, skin, and other gastrointestinal cancer types and that they have the capability to inhibit ROS production in patients [36, 37, 89, 134, 131, 62, 127]. In addition, it was demonstrated that these vitamins can inhibit progression and pathogenesis in colorectal cancer [12]. In animal models, vitamins showed promise for chemopreventive agents against several types of gastrointestinal cancer [62].

With the use of a combination of vitamins, selenium, β-carotene, essential fatty acids, and coenzyme Q10 in patients with breast cancer, it was observed that during the study no patient died, no patient showed signs of further distant metastasis, quality of life improved, and six patients showed apparent partial remission [80]. Human studies demonstrated that consumption of total antioxidants in the diet (fruits and vegetables) is inversely associated with the risk of distal gastric cancer [87]. Antioxidants, especially polyphenols, have been found to be promising agents against cervical cancer, including induction of apoptosis, growth arrest, inhibition of DNA synthesis, and modulation of signal transduction pathway; additionally, polyphenols can interfere with each stage of carcinogenesis initiation, promotion, and progression for the prevention of cancer development [26].

Camelia sinensis tea, which contains a great quantity of polyphenols (epichatechin, (‒)‒epigallocatechin-3-gallate) is the most widely consumed beverage worldwide, and it was demonstrated that consumption of this beverage has shown to afford protection against chemical carcinogen-induced stomach, lung, esophagus, duodenum, pancreas, liver, breast, and colon carcinogenesis in specific bioassay models. The properties of the tea’s polyphenols make them effective chemopreventive agents against the initiation, promotion, and progression stages of multistage carcinogenesis [64]. Rosmanic acid had demonstrated to possess potent anticancer and apoptotic effect in mouse-induced skin cancer [121], curcumin, (‒)‒epigallocatechin-3-gallate, and lovastatin in combination were able to suppress esophageal cancer in mouse [154], and melatonin demonstrated diminishing the development and mortality of mouse implanted with murine hepatoma cells MN22a [39]. It was demonstrated that beta-ionone, a precursor of carotenoids, ameliorated lung carcinogenesis; the latter is attributed to the antiproliferative and antioxidant potential of beta-ionone through free radical scavenging properties [9]. Α-tocopherol showed down-regulation of the expression of the stress-activated genes PKC-α, c-Myc, and Lactate dehydrogenase A (LDHA) in cancerous mice, decreasing cancer cell proliferation [120]. It has been suggested that rosmanic acid suppresses oral carcinogenesis by stimulating the activities of detoxification enzymes, improving the status of lipid peroxidation and antioxidants, and down-regulating the expression of p53 and bcl-2 during 7,12 dimethylbenz(a)anthracene-induced oral carcinogenesis in hamster [8]. In the same manner, the methanolic extract of fennel seed exhibited an antitumoral affect by modulating lipid peroxidation and augmenting the antioxidant defense system in Ehrlich ascites carcinoma- bearing mice with or without exposure to radiation [94]. Silymarin, a natural flavonoid from the milk thistle seed, displayed chemopreventive action against 1,2-dimethylhydrazine plus dextran sodium sulfate-induced inflammation associated with colon carcinogenesis [135]. Quercetin, a flavonoid found in many natural foods, demonstrated to exert a direct oro-apoptotic affect on tumor cells and can indeed block the growth of several human cancer-cell lines in different cell-cycle phases, which have been demonstrated in several animal models [41]. The methanolic extract of Indigofera cassioides was evaluated in terms of their antitumor activity on Ehrlich ascites carcinoma- bearing mice; the extract showed a potent antitumoral effect against tumor cells due its preventing lipid peroxidation and promoting the enzymatic antioxidant defense system in animals [69]. Brucine, a natural plant alkaloid, was reported to possess cytotoxic and antiproliferative activities and also had showed to be a potential anti-metastatic and -angiogenic agent [2].

An in vitro assay demonstrated that the mechanism’s antioxidant action, according to Halliwell [52], can include the following:

  1. suppressing ROS formation either by inhibiting the enzymes or chelating the trace elements involved in free radical production;

  2. scavenging ROS, and

  3. up-regulating or protecting antioxidant defenses.

Flavonoids have been identified as fulfilling the majority of the criteria previously described. Thus, their effects are two-fold as follows:

  1. Flavonoids inhibit the enzymes responsible for superoxide anion production, such as xanthine oxidase [54] and Protein kinase C (PKC) [140], and

  2. Flavonoids have also shown to inhibit cyclo-oxygenase, lipoxygenase, microsomal mono-oxygenase, glutathione S-transferase, mitochondrial succinoxidase, and (Nicoti-namide adenine denucleotide (NADH) oxidase, all of which are involved in ROS generation [68, 15].

A number of flavonoids efficiently chelate trace metals, which play an important role in oxygen metabolism. Free iron and copper are potential enhancers of ROS formation, as exemplified by the reduction of hydrogen peroxide with the generation of the highly aggressive hydroxyl radical [103].

On the other hand, in vitro studies showed that the compounds present in fruits and vegetables, such as resveratrol, genestein, baicalein, and many others are attractive candidates for improved chemotherapeutic agents [35]. Resveratrol in combination with platinum drugs and oxaliplatin demonstrated that resveratrol administered 2 h prior to platinum drugs may sensitize ovarian cancer cells to platinum, inducing apoptosis and providing a means of overcoming resistance [95].

Ren [109] demonstrated that (‒)‒epigallocatechin-3-gallate induces reduction in IM9 myeloma cells and that its activity was dose- and time-dependent on the induction of apoptotic cell death; additionally, this natural metabolite combined with curcumin and lovastatin possessed the ability to suppress esophageal cancer-cell growth [154]. In multilla berries, it was found that their high levels of polyphenols, flavonoids, and flavonols and their antioxidants have a strong ability to reduce the viability of colon-cancer HT-29 and SW480 cell lines [33]. The anticancer activity of baicalein, a flavonoid found in several plants, was evaluated in a cutaneous squamous carcinoma-cell line, A431; it was found that this compound reduced the migration and invasiveness of the cells through inhibition of ezrin expression, which leads to the suppression of tumor metastasis [153].

In beans, it was found that these contain several compounds with cytotoxic activity on animals and human cell lines ( C33-A, SW480, and 3T3), which can be attributed to the antioxidants and damage to DNA caused by tannins, saponins, lectins, and others compounds found in the seed [143, 144].

Melastoma malabathricum showed to have the ability to inhibit the proliferation of Caov-3, HL-60, CEM-SS, MCF-7, HeLa, and MDA-MB-231 cell lines, indicating that the leaves of this plant possess potential antiproliferative and antioxidant activities that could be attributed to its high content of phenolic compounds [122]. Melatonin, a naturally occurring compound, showed cytotoxic activity toward transformed 3T3-SV40 fibroblasts [143] and murine hepatoma cells MN22a, and it was shown that the sensitivities of both cell types to lysis by killer cells fell sharply [139].T he potent antioxidant activity of Kalanchoe gracilis (L.) DC stems due to that the polyphenolic compound found in this medicinal plant showed to have the ability to inhibit HepG2 cell proliferation [171], and the flavonoids found in Rosa canina L. are responsible for the antiproliferative activity in HeLa, MCF7, and HT-29 cancer-cell lines [138]. Analysis of the fruit of Phelaria macrocarpa (Boerl.) Scheff and of Olea europaea L. indicated that all parts of the fruit possess cytotoxic activity against HT-29, MCF-7, HeLa, BPH-1, and Chang cells, indicating that these fruits are a sources of bioactive compounds that are as potent as antioxidants and antioxidant agents, suggesting its possible use as an adjuvant agent in the treatment of cancer [56, 1].

The extract of Calluna vulgaris exhibited a photoprotective effect on human keratinocytes (HaCaT) exposed to Ultraviolet B (UVB) radiation [100]. Cachrys pungens Jan was analyzed in a human tumor- cell line, amelanotic melanoma, and it was found that its extract contains antioxidants, such as coumarins, which are responsible for their cytotoxicity in A375 cells [92]. Inonotus obliquus and Peperomia pellucida, plants employed as folk remedies for cancer treatment, were evaluated in several tumor cell-line types and it was found that these plants contains several antioxidants, such as lanosterol, inotodiols, ergosterol, phytol, 2-naphthalenol, decahydro hexadecanoic acid, methyl ester, and 9,12 octadecadienoic acid, indicating that these antioxidant compounds are responsible for the anticarcinogenic activity of the plant extract [129, 150]. The extract of Indigofera cassioides indicated the presence antioxidant activity, preventing lipid peroxidation and promoting the enzymatic antioxidant defense system, and also showed potent antitumoral and cytotoxic affect against EAC, DLA, HeLa, Hep-2, HepG-2, MCF-7, Ht-29, and NIH 3T3 cells [69].

Hesperetin, hesperetin analog, carnocine, and resveratrol were evaluated for their antioxidant and anticarcinogenic activity on HT-29, HCT116, and mouse skin carcinogenesis; their studies demonstrated that these compounds can inhibit cell proliferation, induce apoptosis, affect glycolysis, and decrease tumoration [125, 161, 40]. Honey, a natural product commonly used throughout the world, contains antioxidant properties and exerts a preventive effect against disease. Chrysin is a natural flavone commonly found in honey, and it was demonstrated that this compound induced apoptosis in PC-3 cells [116], fennel seeds (Foeniculum vulgare) are present in antioxidants that have an anticancer potential against HepG2 and MCF-7 cell lines [94). It was indicated that compounds such as quercetin, flavonoids, and brucine have chemopreventive action against the osteosarcoma cell line (MG63), C6 glioma cells, and Ehrlich ascites cells, and that they can be used as anticancer, antigenotoxic agents and can induce apoptosis [135, 119, 2].

8. Conclusion

Oxidative stress causes injury to cells, induces gene mutation, and is involved in carcinogenesis and other degenerative diseases by directly or indirectly influencing intracellular signal transduction and transcription factors. The state of OS under carcinogenesis and tumor-bearing conditions is an intricate one in which various substances are involved in complex interactions.

The data discussed in this paper show that the biological effects of antioxidants on humans and animals can be controversial. Due to that the action of antioxidants depends on the oxidative status of cells, antioxidants can be protective against cancer; because ROS induce oxidative carcinogenic damage in DNA, antioxidants can prevent cancer in healthy persons harboring increased ROS levels.

Oxidative stress as cause and effect is not the sole factor in the development of cancer. It is important to take into account that there are other factors involved in its development, such as genetic predisposition, eating habits, environment, etc. Because ROS at moderate concentrations act as indispensable mediators of cancer-protective apoptosis and phagocytosis, an excess of antioxidants in persons with low ROS levels can block these cancer-preventive mechanisms. High doses of antioxidants can reduce the ROS level in persons who overproduce ROS and protect them against cancer and other ROS-dependent morbid conditions.

For individuals with low ROS levels, high doses of antioxidants can be deleterious, suppressing the already low rate of ROS generation and ROS-dependent cancer-preventive apoptosis. Screening and monitoring the human population regarding their ROS level can transform antioxidants into safe and powerful disease-preventive tools that could significantly contribute to the nation’s health.

Many in vivo and in vitro studies performed to evaluate the capability of antioxidants against cancer, such as chemopreventive or therapeutic agents, were conduced employing natural antioxidants from fruits and vegetables; these are mainly supplied through food, which often do not provide sufficient input for these to function as chemoprotectors. Thus, humans are forced to consume antioxidants in a more direct manner, either in the form of a tablet, a pill, or any other form in order to supply the levels that the body requires of these compounds to protect it against cell damage caused by oxidation reactions, thus reducing the risk of certain cancer types, especially those of the epithelial surface and in the upper part of the body, such as breast, lung, kidney, liver, intestine, and many others that have been well documented. However, further investigations are expected before our better understanding of the function of many antioxidants and their utilization in the prevention and treatment of cancer and other degenerative diseases.


1 - R Acquaviva, C Di Giacomo, V Sorrenti, F Galvano, R Santangelo, V Cardile, S Gangia, N D’Orazio, NG Abraham, L Vanella, 2012 International Journal of Oncology Antiproliferative effect of oleuropein in prostate cell lines Print 1791-2423 Online 1019-6439 41 31 38
2 - S. S. Agrawal, S. Saraswati, R. Mathur, M. Pandey, 2011 Cytotoxic and antitumor effects of brucine on Ehrlich ascites tumor and human cancer cell line Life Science 89 147 158 0024-3205
3 - P. A. Akah, R. K. Ekekwe, 1995 Ethnopharmacology of some of the asteraceae family used in the Nigerian tradition al medicine. Fitoterapia 66 352 355 0036-7326 X
4 - D. A. Akinpelu, 1999 Antimicrobial activity of Vernonia amygdalina leaves Fitoterapia 70 232 234 0036-7326 X
5 - R. G. Allen, M. Tresini, 2000 Oxidative stress and gene regulation. Free Radical Biology & Medicine 28 463 499 0891-5849
6 - K. Ando, T. Fujita, 2009 Metabolic Syndrome and Oxidative Stress Free Radical Biology & Medicine 47 213 218 0891-5849
7 - AC Andreazza, F Kapczinski, M Kauer-Sant’Anna, JC Walz, DJ Bond, CA Gonçalves, LT Young, LN Yatham, 2009 3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder Journal of Psychiatry and Neuroscience 1488-2434 4 263 271
8 - C Anusuya, S Manoharan, 2011 Journal of Environmental Pathology, Toxicology and Oncology Antitumor initiating potential of rosmarinic acid in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis Print 0731-8898 Online 2162-6537 30 199 211
9 - S. Asokkumar, C. Naveenkumar, S. Raghunandhakumar, S. Kamaraj, P. Anandakumar, S. Jagan, T. Devaki, 2012 Antiproliferative and antioxidant potential of beta-ionone against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice Molecular and Cellular Biochemistry 363 335 345 0300-8177 Print 1573-4919 (Online)
10 - R. Bartoli, F. Fernandez-Banares, E. Navarro, E. Castella, J. Mane, M. Alvarez, C. Pastor, E. Cabre, M.A. Gassull, 2000 Effect of olive oil on early and late events of colon carcinogenesis in rats: Modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis Gut 46 191 199 0017-5749 Print 1468-3288 (Online)
11 - BS Berlett, E. R. Stadtman, 1997 Protein Oxidation in Aging, Disease, and Oxidative Stress The Journal Of Biological Chemistry 272 33 20313 20316 0021-9258 Print 1083-351X (Online)
12 - S. S. Bhagat, R. A. Ghone, A. N. Suryakar, P. S. Hundekar, 2011 Lipid peroxidation and antioxidant vitamin status in colorectal cancer patients Indian Journal Physiology and Pharmacology 55 72 76 0019-5499
13 - V. Bohr, S. Anson, R. M. Mazur, G. Dianov, 1998 Oxidative DNA damage processing and changes with aging Toxicology Letters Vols 102-103 47 52 0378-4274
14 - H. Boon, M. Stewart, MA Kennard, R. Gray, C. Sawka, J. B. Brown, C. Mc William, A. Garvin, R. A. Baron, D. Aaron, T. Haines-Kamka, 2000 Use of complementary/alternative medicine by breast cancer survivors in Ontario: prevalence and perceptions Journal of Clinical Oncology 8 2515 2521 0073-2183 X
15 - J. E. Brown, H. Khodr, R. C. Hider, C. Rice-Evans, 1998 Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties. Biochemical Journal 330 1173 1178 0264-6021 Print 1470-8728 (Online)
16 - N. S. Brown, R. Bicknell, 2001 Hypoxia and oxidative stress in breast cancer: Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer Breast Cancer Research 3 323 327 0167-6806 Print 1573-7217 (Online)
17 - J. Cadet, T. Douki, J. L. Ravanat, 1997 Artifacts associated with the measurement of oxidized DNA bases. Environmental Health Perspectives 105 1034 1039 0091-6765
18 - M. Calomme, L. Pieters, A. Vlietinck, Berghe. D. Vanden, 1996 Inhibition of bacterial mutagenesis by Citrus flavonoids. Planta Medica 62 222 226 0032-0943
19 - M. H. Carlsen, B. L. Halvorsen, K. Holte, S. K. Bøhn, S. Dragland, L. Sampson, C. Willey, H. Senoo, Y. Umezono, C. Sanada, I. Barikmo, N. Berhe, W. C. Willett, K. Phillips, D. R. Jr Jacobs, R. Blomhoff, 2010 The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide Nutrition Journal 9 3 1475-2891
20 - P. Cejas, E. Casado, C. Belda-Iniesta, J. De Castro, E. Espinosa, A. Redondo, M. Sereno, M. A. García-Cabezas, J. A. Vara, A. Domínguez-Cáceres, R. Perona, M. González-Barón, 2004 Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain) Cancer Causes and Control 15 707 719 0957-5243 Print 1573-7225 (Online)
21 - L Chen, JY Hu, SQ Wang, 2012 The role of antioxidants in photoprotection: A critical review Journal of the American Academy of Dermatology 10.1016/j.jaad.2012.02.009 [Epub ahead of print] 0190-9622 0190 9622
22 - R. Chinery, J. A. Brockman, M. O. Peeler, Y. Shyr, R. D. Beauchamp, R. J. Coffey, 1997 Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21WAF1/CIP1 via C/EBP Nature Medicine 3 1233 1241 1078-8956
23 - F. Dal-Pizzol, C. Ritter, Oj. Cassol Jr, G. T. Rezin, F. Petronilho, A. I. Zugno, J. Quevedo, E. L. Streck, 2009 Oxidative Mechanisms of Brain Dysfunction During Sepsis Neurochemical Research 35 1 12 DOI: s11064-009-0043-4 0364-3190 Print 1573-6903 (Online)
24 - O. L. Delgado, C. G. Betanzos, M. M. T. Sumaya, 2010 Importancia de los antioxidantes dietarios en la disminución del estrés oxidativo Investigación y Ciencia 50 10 15 1665-4412
25 - E. G. De Mejia, M. C. Valadez-Vega, R. Reynoso-Camacho, G. Loarca-Pina, 2005 Tannins, trypsin inhibitors and lectin cytotoxicity in tepary (Phaseolus acutifolius) and common (Phaseolus vulgaris) beans Plant Foods Hum Nutr 60 137 145 0921-9668
26 - F Di Domenico, Coccia Foppoli, R C, M Perluigi, 2012 Antioxidants in cervical cancer: Chemopreventive and chemotherapeutic effects of polyphenols Biochimica et Biophysica Acta 0005-2736 1822 737 747
27 - J. A. Drisko, J. Chapman, V. J. Hunter, 2003 The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer Journal of the American College of Nutrition 22 118 123 1665-4412
28 - S. J. Duthie, V. L. Dobson, 1999 Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro European Journal of Nutrition 38 28 34 0022-3166 Print 1541-6100 (Online)
29 - O. Ebenezer, A. Farombi, Olatunde 2011 Antioxidative and chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoid International Juornal of Environment Researc and Public Health 8 2533 2555 1661-7827 Print 1660-4601 (Online)
30 - M. A. M. Echart, L. J. P. Barrio, Gabriela. Maria, G. M. G. Valle, S. C. H. Augustin, MI Ugalde Marques da Rocha, MF Manica-Cattani, G Feyl dos Santos, IB Manica da Cruz, 2009 Association between manganese superoxide dismutase (MnSOD). gene polymorphism and elderly obesity Molecular and Cellular Biochemistry 328 33 40 0300-8177 Print 1573-4919 (Online)
31 - E. Ernst, B. R. Cassileth, 1998 The prevalence of complementary/alternative medicine in cancer: a systematic review. Cancer 83 777 782 0000-8543 X (Print) 1097-0142 (Online)
32 - H. Esterbauer, J. S. Schauur, H. Zollner, 1991 Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes Free Radical Biology & Medicine 11 81 128 0891-5849
33 - S. Flis, Z. Jastrzebski, J. Namiesnik, P. Arancibia-Avila, F. Toledo, H. Leontowicz, M. Leontowicz, M. Suhaj, S. Trakhtenberg, S. Gorinstein, 2012 Evaluation of inhibition of cancer cell proliferation in vitro with different berries and correlation with their antioxidant levels by advanced analytical methods Journal of Pharmaceutical Biomedical Analysis 62 68 78 0731-7085
34 - R. A. Floyd, J. J. Watson, P. K. Wong, 1986 Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation Free Radical Research Communications 1 163 172 8755-0199
35 - J. T. Fox, S. Sakamuru, R. Huang, N. Teneva, S. O. Simmons, M. Xia, R. R. Tice, CP Austin, K. Myung, 2012 High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death Proceedings of the National Academy of Sciences of United States of America 109 5423 5428
36 - V. Fuchs-Tarlovsky, M. Bejarano-Rosales, G. Gutierrez-Salmeán, MA Casillas, J. C. López-Alvarenga, G. M. Ceballos-Reyes, 2011 Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer Nutrición Hospitalaria 26 819 826 0212-1611
37 - H Fukumura, M Sato, K Kezuka, I Sato, X Feng, S Okumura, T Fujita, U Yokoyama, H Eguchi, Y Ishikawa, T Saito, 2012 Effect of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia in prostate cancer cells. The Jornal of Physiological Sciences 1880-6546 (Print) 1880-6562 Online 62 251 257
38 - M. Gago-Dominguez, X. Jiang, J. E. Castelao, 2007 Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis Breast Cancer 9 1 11 10.1186/bcr1628 0146-5542 X
39 - I. A. Gamaleĭ, K. M. Kirpichnikova, N. A. Filatova, 2011 Effect of melatonin on the functional properties of transformed cells Vopr Onkol 57 481 485 0507-3758
40 - J George, M Singh, AK Srivastava, K Bhui, P Roy, PK Chaturvedi, Y Shukla, 2011 Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53 PLoS One 1932-6203 6 23395 23408
41 - L. Gibellini, M. Pinti, M. Nasi, J. P. Montagna, S. De Biasi, E. Roat, L. Bertoncelli, E. L. Cooper, A. Cossarizza, 2011 Quercetin and cancer chemoprevention Evidence-Based Complementary and Alternative Medicine 59 1356 1365 0174-1427 Print 1741-4588 (Online)
42 - C. I. Gill, A. Boyd, E. Mc Dermott, M. Mc Cann, M. Servili, R. Selvaggini, A. Taticchi, S. Esposto, G. Montedoro, H. Mc Glynn, I. Rowland, 2005 Potential anti-cancer effects of virgin olive oil phenols on colorectal carcinogenesis models in vitro. International Journal of Cancer 117 1 7 0020-7136 1097-0215 (Online)
43 - G Gille, K Sigler, 1995 Folia Microbiological Oxidative stress and living cells 0015-5632 (Print) 1874-9356 (Online) 40 131 152
44 - G. Gong, G. Waris, R. Tanveer, A. Siddiqui, 2001 Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-B Proceedings of the National Academy of Sciences of United States of America 98 17 9599 9604 0027-8424
45 - P. A. Grimsrud, H. Xie, T. J. Griffin, D. A. Bernlohr, 2008 Oxidative Stress and Covalent Modification of Protein with Bioactive Aldehydes Journal of Biological Chemistry 283 32 21837 21841 0021-9258 (Print) 1083-351X (Online)
46 - V Gupta, M Sharma, 2012 Phytochemical Analysis and Evaluation of Antioxidant Activities of Methanolic Extracts of Maytenus emarginata 1536-2310 (Print) 1557-8100 Online 5 16 257 262
47 - B. Halliwell, 1994 Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? The Lancet 344 721 724 1040-6736
48 - B. Halliwell, 1996 Antioxidants in Human Health and Disease. Annual Reviews, 16 33 50 1550-8382 Online
49 - B. Halliwell, 2000 The antioxidant paradox. The Lancet 1 1179 1180 1040-6736
50 - B. Halliwell, J. M. C. Gutteridge, 2006 Free Radicals in Biology and Medicine Ed 4. Clarendon Press, Oxford
51 - B. Halliwell, 2007 Oxidative stress and cancer: have we moved forward? Biochemical Journal 401 1 11 0264-6021 Print 1470-8728 (Online)
52 - B. Halliwell, 2008 Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Archives of Biochemistry and Biophysics 476 107 112 0003-9861 Print 1096-0384 (Online)
53 - R.M. Han, Y.X. Tian, E.M. Becker, M.L. Andersen, J.P. Zhang, L.H. Skibsted, 2007 Journal of Agricultural and Food Chemistry Puerarin and conjugate bases as radical scavengers and antioxidants: molecular mechanism and synergism with beta-carotene 0021-8561 Print 1520-5118 Online 55 2384 2389
54 - Y. Hanasaki, S. Ogawa, S. Fukui, 1994 The correlation between active oxygens scavenging and antioxidative effects of flavonoids Free Radical Biology & Medicine 16 845 850 0891-5849
55 - Y. Z. Hashim, I. R. Rowland, H. Mc Glynn, M. Servili, R. Selvaggini, A. Taticchi, S. Esposto, G. Montedoro, L. Kaisalo, K. Wahala, C. I. Gill, 2008 Inhibitory effects of olive oil phenolics on invasion in human colon adenocarcinoma cells in vitro International Journal of Cancer 122 495 500 0020-7136 Print 10970215 Online
56 - R. Hendra, S. Ahmad, E. Oskoueian, A. Sukari, M. Y. Shukor, 2011 Antioxidant, anti-inflammatory and cytotoxicity of Phaleria macrocarpa (Boerl.) Scheff Fruit BMC Complemententary & Alternative Medicine 11 110 121 1472-6882
57 - S. Hippeli, I. Heiser, E. F. Elstner, 1999 Activated oxygen and free oxygen radicals in pathology: New insights and analogies between animals and plants Plant Physiology Biochemistry 37 167 178 0981-9428
58 - C. Hladik, S. Krief, C. Haxaire, 2005 Ethnomedicinal and bioactive properties of plants ingested by wild chimpanzees in Uganda Journal Ethnopharmacology 101 1 5 0378-8741
59 - M.L. Hu, 2011 Chang Gung Medical Journa Dietary Polyphenols as Antioxidants and Anticancer Agents: More Questions than Answers 2072-0939 34 449 459
60 - M. Inoue, K. Tajima, M. Mizutani, H. Iwata, T. Iwase, S. Miura, K. Hirose, N. Hamajima, S. Tominaga, 2001 Regular consumption of green tea and the risk of breast cancer recurrence: Follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. Cancer Letters 167 175 182 0304-3835
61 - B. Iovine, M. L. Iannella, F. Nocella, M. R. Pricolo, MA Bevilacqua, 2012 Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS production Cancer Letters 28 122 128 0304-3835
62 - V. Jayaprakash, J. R. Marshall, 2011 Selenium and other antioxidants for chemoprevention of gastrointestinal cancers Best Practtice & Research Clinical Gastroenterology 25 507 518 1521-6918
63 - M. Jisaka, H. Ohigashi, K. Takegawa, M. Hirota, R. Irie, MA Huffman, K. Koshimizu, 1993 Steroid glucosides from Vernonia amygdalina, a possible chimpanzee plant. Phytochemistry 34 409 413 0031-9422
64 - S. K. Katiyar, H. Mukhtar, 1997 Tea antioxidants in cancer chemoprevention Journal of Cellular Biochemistry 27 59 67 1097-4644
65 - J.N. Keller, 2006 Interplay Between Oxidative Damage, Protein Synthesis, and Protein Degradation in Alzheimer’s Disease Journal of Biomedicine and Biotechnology 1110-7243 Print 1110-7251 Online 2006 1 3
66 - N. Khan, F. Afaq, M. Saleem, N. Ahmad, H. Mukhtar, 2006 Targeting multiple signaling pathways by green tea polyphenol (−)-epigallocatechin-3-gallate Cancer Research 66 2500 2505 0008-5472 Print 1538-7445 Online
67 - C. Kleinschnitz, H. Grund, K. Wingler, ME Armitage, J. Jones, M. Mittal, D. Barit, T. Schwarz, C. Geis, P. Kraft, K. Barthel, M. K. Schuhmann, A. M. Herrmann, S. G. Meuth, G. Stoll, S. Meurer, A. Schrewe, L. Becker, V. Gailus-Durner, H. Fuchs, T. Klopstock, M. Hrabe´ de Angelis, K. Jandeleit-Dahm, A. M. Shah, N. Weissmann, H. H. H. W. Schmidt, 2010 Post-Stroke Inhibition of Induced NADPH Oxidase Type 4Prevents Oxidative Stress and Neurodegeneration PloS Biology 8 9 1545-7885 1544-9173
68 - L. G. Korkina, I. B. Afanas’ev, 1997 Antioxidants in Disease Mechanisms and Therapy Sies, H., Ed.; Academic Press: San Diego 151 163
69 - RS Kumar, B Rajkapoor, P Perumal, 2011 Ex. DC. Asian Pacific Journal of Tropical Medicine In vitro and in vivo anticancer activity of Indigofera cassioides Rottl 1995-7645 4 379 385
70 - C. La Vecchia, A. Altieri, A. Tavani, 2001 Vegetables, fruit, antioxidants and cancer: a review of Italian studies European Journal of Nutrition 40 261 267 1436-6207 Print 1436-6215 Online
71 - Z. R. Lai, Y. L. Ho, S. C. Huang, T. H. Huang, S. C. Lai, J. C. Tsai, C. Y. Wang, G. J. Huang, Y. S. Chang, 2011 Antioxidant, anti-inflammatory and antiproliferative activities of Kalanchoe gracilis (L.) DC stem. The American Journal of Chinese Medicine 39 1275 1290 0019-2415 X Print 1793-6853 Online
72 - CA Larsen, R. H. Dashwood, 2009 Suppression of Met activation in human colon cancer cells treated with (−)-epigallocatechin-3-gallate: Minor role of hydrogen peroxide Biochemical and Biophysical Research Communnications 389 527 530 0000-6291 X
73 - C. K. Lee, R. Weindruch, T. A. Prolla, 2000 Gene-expression profile of the ageing brain in mice Nature Genetics 25 294 297 1061-4036
74 - H. Leong, P. S. Mathur, G. L. Greene, 2008 Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea. Breast Cancer Research and Treatment 107 359 369 0167-6806 Print 0167-6806 Print 1573-7217 Online
75 - Q. Li, H. F. Zhao, Z. F. Zhang, Z. G. Liu, X. R. Pei, J. B. Wang, M. Y. Cai, Y. Li, 2009 Long-term administration of green tea catechins prevents age-related spatial learning and memory decline in C57BL/6 J mice by regulating hippocampal cyclic AMP-response element binding protein signaling cascade Neuroscience 159 1208 1215 0306-4522
76 - W. Li, Y. H. Shi, R. L. Yang, J. Cui, Y. Xiao, B. Wang, G. W. Le , 2010 Effect of somatostatin analog on high-fat diet-induced metabolic syndrome: Involvement of reactive oxygen species Peptides 31 4 625 629 0196-9781
77 - W. Liang, X. Li, C. Li, L. Liao, B. Gao, H. Gan, Z. Yang, L. Liao, X. Chen, 2011 Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells Molecular Medicine Reports 4 1017 1023 1791-2997 Print 1791-3004 Online
78 - M. Liu, X. Gong, R. K. Alluri, J. Wu, T. Sablo, Z. Li, 2012 Characterization of RNA damage under oxidative stress in Escherichia coli Biol Chem 393 3 123 132 1437-4315
79 - X. Llor, E. Pons, A. Roca, M. Alvarez, J. Mane, F. Fernandez-Banares, M. A. Gassull, 2003 The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes Clinical Nutrition 22 71 79 0261-5614
80 - K. Lockwood, S. Moesgaard, T. Hanioka, K. Folkers, 1994 Apparent partial remission of breast cancer in ‘High Risk’ patients supplemented with nutritional antioxidants, essential fatty acids and Coenzyme Q10 Biochemical and Biophysical Research Communications 15 231 s240 0000-6291 X
81 - Q Ma, K. Kinneer, 2002 Chemoprotection by phenolic antioxidants. Inhibition of tumor necrosis factor alpha induction in macrophages Journal of Biological Chemistry 0021-9258 Print 1083-351X Online 277 2477 2484
82 - A. C. Maritim, R. A. Sanders, I. I. I. J. B. Watkins, 2003 Diabetes, Oxidative Stress, and Antioxidants: A Review Journal of Biochememical Molecular and Toxicology 17 24 38 1095-6670 Print 1099-0461 Online
83 - W. R. Markesbery, 1997 Oxidative Stress Hypothesis In Alzheimer’s Disease Free Radical Biology & Medicine 23 1 134 147 0891-5849
84 - M. E. Martinez, 2005 Primary prevention of colorectal cancer: Lifestyle, nutrition, exercise Recent Results in Cancer Research 166 177 211 0080-0015
85 - JM Matés, JA Segura, FJ Alonso, J. Márquez, 2011 Current Medicinal Chemistry Anticancer antioxidant regulatory functions of phytochemicals 0929-8673 Print 1875-533X Online 18 2315 2338
86 - J. M. Mates, C. Perez-Gomez, I. Nunez de Castro, 1999 Antioxidant enzymes and human diseases. Clinical Biochemistry 32 595 603 0009-9120
87 - S. Mauro, B. Rino, W. Alicja, ME (2002. Anna, 2002 Total antioxidant potential of fruit and vegetables and risk of gastric cancer Gastroenterology 123 985 991 0016-5085
88 - A. Maxmen, 2012 The Hard Facts Nature 485 S50 S51 0028-0836
89 - H. Mazdak, H. Zia, 2012 Vitamin e reduces superficial bladder cancer recurrence: a randomized controlled trial International Journal of Preventive Medicine 3 110 115
90 - J. M. McCord, I. Fridovich, 1968 The Journal of Bioogical Chemistry The reduction of cytochrome c by milk xanthine oxidase 2008-7802 Print 2008-8213 Online 243 5753 5760
91 - L. Medina-Ceja, H. Guerrero-Cazares, A. Canales-Aguirre, A. Morales-Villagrán, A. Feria-Velasco, 2007 Características estructurales y funcionales de los transportadores de glutamato: su relación con la epilepsia y el estrés oxidativo Revista de Neurología 45 6 341 352
92 - G Menichini, C Alfano, E Provenzano, M Marrelli, GA Statti, F Menichini, F Conforti, 2012 Cachrys pungens Jan inhibits human melanoma cell proliferation through photo-induced cytotoxic activity Cell Proliferation 0960-7722 Print 1365-2184 Online 45 39 47
93 - E. Jr Middleton, C. Kandaswami, T. C. Theoharides, 2000 The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer Pharmacological Reviews 52 673 751 0031-6997
94 - R. H. Mohamad, A. M. El -Bastawesy, M. G. Abdel-Monem, A. M. Noor, H. A. Al-Mehdar, S. M. Sharawy, MM El -Merzabani, 2011 Antioxidant and anticarcinogenic effects of methanolic extract and volatile oil of fennel seeds (Foeniculum vulgare) Journal of Medicine Food, 14 986 1001 0109-6620 Print 1557-7600 Online
95 - M. U. Nessa, P. Beale, C. Chan, J. Q. Yum, F. Huq, 2012 Combinations of resveratrol, cisplatin and oxaliplatin applied to human ovarian cancer cells Anticancer Res 32 53 59 0250-7005 Print 1791-7530 Online
96 - N. Noda, H. Wakasugi, 2000 Cancer and oxidative stress Journal of the Japan Medical Association 124 11 1571 1574 1356-8650
97 - A. Nunomura, K. Honda, A. Takeda, K. Hirai, X. Zhu, M. A. Smith, G. Perry, 2006 Oxidative Damage to RNA in Neurodegenerative Diseases Journal of Biomedicine and Biotechnology 82323 1 6 1110-7243 Print 1110-7251 Online
98 - N. Nyström, 2005 Role of oxidative carbonylation in protein quality control and senescence EMBO Journal 0261-4189 Print 1460-2075 Online 24 1311 1317
99 - R. W. Owen, A. Giacosa, W. E. Hull, R. Haubner, B. Spiegelhalder, H. Bartsch, 2000 The antioxidant/anticancer potential of phenolic compounds isolated from olive oil European Journal Cancer 36 1235 1247 0959-8049
100 - M Perde-Schrepler, G Chereches, L Brie, P Virag, O Barbo,s, O Soritau, C Tatomir, E Fischer-Fodor, A Filip, L Vlase, ID Postescu, 2011 Photoprotective effect of Calluna vulgaris extract against UVB-induced phototoxicity in human immortalized keratinocytes. Journal of Environment Pathology Toxicology and Oncology 0371-8898 Print 2162-6537 Online 30 323 331
101 - R. M. Perera, N. Bardeesy, 2011 When antioxidants are bad Nature 4 4 0028-0836
102 - D. Pietá, Lima. M. N. Martins De, J. Presti-Torres, A. Dornelles, V. A. Garcia, S. F. Siciliani, M. G. Rewsaat, L. Constantino, P. Budni, F. Dal-Pizzol, N. Schrödera, 2007 Memantine Reduces Oxidative Damage And Enhances Long-Term Recognition Memory In Aged Rats Neuroscience 146 1719 1725 0306-4522
103 - P. G. Pietta, 2000 Flavonoids as Antioxidants Journal of Natural Produts 1035 1042 0163-3864 Print 1520-6025 Online
104 - B. Plaumann, M. Fritsche, H. Rimpler, G. Brandner, R. D. Hess, 1996 Flavonoids activate wild-type p53 Oncogene 13 1605 1614 0950-9232
105 - K. N. Prasad, A. Kumarm, V. Kochupillaim, W. C. Colem, 1999 High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy Journal of the American College of Nutrition 18 13 25 0731-5724 Print 1541-1087 Online
106 - K. N. Prasad, W. C. Cole, B. Kumar, K. C. Prasad, 2001 Scientific rationale for using high-dose multiple micronutrients as an adjunct to standard and experimental cancer therapies Journal of the American College of Nutrition 20 450S 463S 0731-5724 Print 1541-1087 Online
107 - T. O. Price, N. Ercal, R. Nakaoke, W. A. Banks, 2005 HIV-1viralproteins gp120 and Tatinduceoxidativestress in brain endothelial cells Brain Research 1045 57 63 0006-8993
108 - J. P. Rabek, I. I. I. W. H. Boylston, J. Papaconstantinou, 2003 Carbonylation of ER chaperone proteins in aged mouse liver Biochemical and Biophysical Research Communications 305 566 572 0000-6291 X
109 - L. Ren, H. Y. Yang, H. I. Choi, K. J. Chung, U. Yang, I. K. Lee, H. J. Kim, DS Lee, B. J. Park, T. H. Lee, 2011 The role of peroxiredoxin V in (-)-epigallocatechin 3-gallate-induced multiple myeloma cell death Oncology Research 19 391 398 0965-0407
110 - KM Rieger-Christ, R Hanley, C Lodowsky, T Bernier, P Vemulapalli, M Roth, J Kim, AS Yee, SM Le, PJ Marie, JA Libertino, IC Summerhayes, 2007 The green tea compound, (−)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cells Journal of Cellular Biochemistry 0730-2312 Print 1097-4644 Online 102 377 388
111 - N. H. Riordan, H. D. Riordan, Y. L. Meng, J. A. Jackson, 1995 Intravenous ascorbate as a tumor cytotoxic. chemotherapeutic agent Medical Hypotheses 44 207 213 0306-9877
112 - N. H. Riordan, H. D. Riordan, J. P. Casciari, 2000 Clinical and experimental experiences with intravenous vitamin C Journal of Orthomolecular Medicine 5 201 213 0317-0219
113 - MA Rivas, R. P. Carnevale, C. J. Proietti, C. Rosemblit, W. Beguelin, M. Salatino, E. H. Charreau, I. Frahm, S. Sapia, P. Brouckaert, P. V. Elizalde, R. Schillaci, 2008 TNF alpha acting on TNFR1 promotes breast cancer growth via P42 P44 MAPK, JNK, Akt and NF-kappa B-dependent pathways Experimental Cell Research 314 3 509 29 0014-4827
114 - C. K. Roberts, R. J. Barnarda, R. K. Sindhub, M. Jurczak, A. Ehdaieb, N. D. Vaziri, 2006 Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome Metabolism Clinical and Experimental 55 928 934 1532-8600
115 - CE Roche, A. D. Romero, 1994 Estrés oxidativo y degradación. de proteínas Medicina clínica 5 103 189 196 0025-7753
116 - S Samarghandian, JT Afshari, S Davoodi, 2011 Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3 Clinics (Sao Paulo) 1807-5932 Print 1980-5322 Online 66 1073 1079
117 - CA Schmitt, S. W. Lowe, 1999 Apoptosis and therapy The Journal of Pathololy 187 127 137
118 - L. B. Seef, K. L. Lindsay, B. R. Bacon, F. Kresina, H. Hoofnagle, 2001 Complementary and alternative medicine in chronic liver disease Hepatology 34 595 603 1096-9896 Online
119 - H Seibert, E Maser, K Schweda, S Seibert, M Gülden, 2011 Cytoprotective activity against peroxide-induced oxidative damage and cytotoxicity of flavonoids in C6 rat glioma cells. Food and Chemical Toxicology 0278-6915 49 2398 2407
120 - R. Sharma, M. Vinayak, 2012 Antioxidant α-tocopherol checks lymphoma promotion via regulation of expression of protein kinase C-α and c-Myc genes and glycolytic metabolism. Leukemia & Lymphoma 1042-8194 Print 1029-2403 Online 6 53 1203 1210
121 - R. Sharmila, S. Manoharan, 2012 Anti-tumor activity of rosmarinic acid in 7,12-dimethylbenz(a) anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice Indian Journal of Experimental Biology 50 187 194 0975-1009 Print 0019-5189 Online
122 - Z. A. Zakaria, MS Rofiee, A. M. Mohamed, L. K. the, M. Z. Salleh, 2011 In vitro antiproliferative and antioxidant activities and total phenolic contents of the extracts of Melastoma malabathricum leaves Journal of Acupuncture and Meridian Studies 4 4 248 256 0000-0020
123 - H. Sies, 1997 Antioxidants in Disease Mechanisms and Therapy Advances in Pharmacology 38 Academic Press: San Diego
124 - H. Sies, 1997 Oxidative Stress: Oxidants And Antioxidants Experimental Physiology 82 291 295 0958-0670 Print 1469-445X Online
125 - G. Sivagami, R. Vinothkumar, CP Preethy, A. Riyasdeen, MA Akbarsha, V. P. Menon, N. Nalini, 2012 Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line- A comparative study Food and Chemical Toxicology 50 660 671 0278-6915
126 - J. Skalicky, V.,. Muzakova, Kandar. R. Roman, M. Meloun, T. Rousar, V. Palicka, 2008 Evaluation of oxidative stress and inflammation in obese adults with metabolic syndrome Clinical Chemistry and Laboratory Medicine 46 4 499 505 1434-6621 Print 1437-4331 Online
127 - T. J. Slaga, 1995 Inhibition of the induction of cancer by antioxidants Advances in Experimental Medicine and Biology 369 167 174 0065-2598
128 - M Solanas, A Hurtado, I Costa, R Moral, J.A. Menendez, R. Colomer, E. Escrich, 2002 International Journal of Oncology Effects of a high olive oil diet on the clinical behavior and histopathological features of rat DMBA-induced mammary tumors compared with a high corn oil diet 1791-2423 21 745 753
129 - Y Sun, T Yin, XH Chen, G Zhang, RB Curtis, ZH Lu, JH Jiang, 2011 In vitro antitumor activity and structure characterization of ethanol extracts from wild and cultivated Chaga medicinal mushroom, Inonotus obliquus (Pers.:Fr.) Pilát (Aphyllophoromycetideae) International Journal of Medical Mushrooms 1521-9437 Print 1940-4344 Online 13 121 130
130 - YJ. Surh, 2003 Cancer chemoprevention with dietary phytochemicals Nature Review Cancer 3 768 780 1097-0142 Online
131 - M. Szpetnar, P. Matras, M. Kiełczykowsk,a, A. Horecka, L. Bartoszewska, K. Pasternak, S. Rudzki, 2012 Antioxidants in patients receiving total parenteral nutrition after gastrointestinal cancer surgery Cell Biochemistry and Funciont 30 211 216 1099-0844 Online
132 - M Takada, Y. Ku, K Habara, T. Ajiki, Y. Suzuki, Y. Kuroda, 2002 Inhibitory effect of epigallocatechin-3-gallate on growth and invasion in human biliary tract carcinoma cells World Journal of Surgery 0364-2313 Print 1432-2323 Online 26 683 686
133 - M. Takada, Y. Nakamura, T. Koizumi, H. Toyama, T. Kamigaki, Y. Suzuki, Y. Takeyama, Y. Kuroda, 2002 Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate Pancreas 25 45 48 0885-3177 Print 1536-4828 Online
134 - D. Thapa, R. Ghosh, 2012 Antioxidants for prostate cancer chemoprevention: Challenges and opportunities Biochemical Pharmacology 83 1319 1330 0006-2952
135 - N Toyoda-Hokaiwado, Y Yasui, M Muramatsu, K Masumura, M Takamune, M Yamada, T Ohta, T Tanaka, T. Nohmi, 2011 Chemopreventive effects of silymarin against 1,2-dimethylhydrazine plus dextran sodium sulfate-induced inflammation-associated carcinogenicity and genotoxicity in the colon of gpt delta rats Carcinogenesis 0143-3334 Print 1460-2180 Online 32 1512 1517
136 - MD Toyokuni, 1998 Oxidative Stress and Cancer: The Role of Redox Regulation Shinya Biotherapy 11 147 154 0092-1299 X Print 1573-8280 Online
137 - S. Tsaluchidu, M. Cocchi, L. Tonello, B. K. Puri, 2008 Fatty acids and oxidative stress in psychiatric disorders BMC Psychiatry 8 1 S1 S5 0147-1244 X Online
138 - V. T. Tumbas, J. M. Canadanović-Brunet, D. D. Cetojević-Simin, G. S. Cetković, S. M. Ethilas, L. Gille, 2012 Effect of rosehip (Rosa canina L.) phytochemicals on stable free radicals and human cancer cells Journal of the Science of Food and Agriculture 92 1273 1281 0022-5142 Print 1097-0010 Online
139 - B. L. Upham, J. G. Wagner, 2001 Toxicological Highlight Toxicant-Induced Oxidative Stress in Cancer Toxicological sciences 64 1 3 1096-6080 Print 1096-0929 Online
140 - F. Ursini, M. Maiorino, P. Morazzoni, A. Roveri, G. Pifferi, 1994 A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation Free Radical Biology & Medicine 16 547 553 0891-5849
141 - B. Uttara, A. V. Singh, P. Zamboni, R. T. Mahajan, 2009 Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options Current Neuropharmacology 7 65 74 0157-0159 X
142 - M. J. Van Erk, P. Roepman, T. R. van der Lende, R. H. Stierum, J. M. Aarts, P. J. van Bladeren, B. van Ommen, 2005 Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro European Journal of Nutrition 44 143 156 1436-6207 Print 1436-6215 Online
143 - C. Valadez-Vega, A. M. Guzmán-Partida, F. J. Soto-Cordova, G. Alvarez-Manilla, J. A. Morales-González, E. Madrigal-Santillán, J. R. Villagómez-Ibarra, C. Zúñiga-Pérez, J. Gutiérrez-Salinas, MA Becerril-Flores, 2011 Purification, biochemical characterization, and bioactive properties of a lectin purified from the seeds of white tepary bean (phaseolus acutifolius variety latifolius) Molecules 21 2561 2582 1420-3049
144 - C. Valadez-Vega, G Alvarez-Manilla, L Riverón-Negrete, A García-Carrancá, JA Morales-González, C Zuñiga-Pérez, E Madrigal-Santillán, J Esquivel-Soto, C Esquivel-Chirino, R Villagómez-Ibarra, M Bautista, A Morales-González, 2011 Detection of cytotoxic activity of lectin on human colon adenocarcinoma (Sw480) and epithelial cervical carcinoma (C33-A) Molecules 1420-3049 2 2107 2118
145 - SD Varma, S. Devamanoharan, SM Morris, 1995 Prevention of cataracts by nutritional and metabolic antioxidants Crititical Reviews in Food Science and Nutrition 35 111 129 1040-8398 Print 1549-7852 Online
146 - D Vauzour, A Rodriguez-Mateos, G Corona, MJ Oruna-Concha, JPE Spence, 2010 Polyphen ols and Human Health: Prevention of Disease and Mechanisms of Action Nutrients 2072-6643 2 1106 1131
147 - O. Warburg, 1956 On the origin of cancer cells Science 123 309 314 0036-8075 Print 1095-9203 Online
148 - G. Waris, A. Siddiqui, 2005 Hepatitis C virus stimulates the expression of cyclooxygenase-2 via oxidative stress: role of prostaglandin E2 in RNA replication Journal of Virology 79 9725 34 0002-2538 X Print 1098-5514 Online
149 - D. D. M. Wayner, G. W. Burton, K. U. Ingold, L. R. C. Barclay, S. J. Locke, 1987 The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma Biochemica et Biophysica Acta 924 408 419 0006-3002
150 - L. S. Wei, W. Wee, J. Y. Siong, D. F. Syamsumir, 2011 Charactetization of anticancer, antimicrobial, antioxidant properties and chemical composition of Peperomia pellucid Acta Medica Iranica 49 670 674 0044-6025 Print 1735-9694 Online
151 - N. I. Weijl, F. J. Cleton, S. Osanto, 1997 Free radicals and antioxidants in chemotherapy induced toxicity Cancer Treatment Reviews 23 209 240 0305-7372 Print
152 - LC Winslow, DJ Krol, 1998 Herbs as medicines Archives Internal Medicine 0003-9926 Print 1538-3679 Online 1258 2192 219
153 - B Wu, J Li, D Huang, W Wang, Y Chen, Y Liao, X Tang, H Xie, F Tang, 2011 Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through Ezrin in A431 cells 1471-2407 11 527 536
154 - F Ye, GH Zhang, BX Guan, XC Xu, 2012 World Journal of Gastroenterology Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin 1007-9327 Print 2219-2840 Online 18 126 135