Plants with anticancer activity addressed in this chapter, parts preferentially used, presumed constituents with anticancer and chemoprotective activity, and references supporting these activities.
Despite much progress in our understanding of the essence of cancer, remarkable advances in methods for early diagnosis, the expanding array of antineoplastic drugs and treatment modalities, as well as important refinements in their use, this disease is among the leading causes of morbidity and mortality in many parts of the world. In fact, the next decade is anticipated to bring over 20 million new cases per year globally, about half of whom will die from their disease. This indicates a need for better strategies to deal with cancer. One way to go forward is to draw lessons from ancient ethnopharmacological wisdom and to evaluate the plant biodiversity for compounds with potential antineoplastic activity. This approach has already yielded many breakthrough cytotoxic drugs such as vincristine, etoposide, paclitaxel, and irinotecan. The Republic of Suriname (South America), renowned for its pristine and highly biodiverse rain forests as well as its ethnic, cultural, and ethnopharmacological diversity, could also contribute to these developments. This chapter addresses the cancer problem throughout the world and in Suriname, extensively deals with nine plants used for treating cancer in the country, and concludes with their prospects in anticancer drug discovery and development programs.
- medicinal plants
- traditional uses
- anticancer activity
Cancer is a generic term to describe over 200 distinct disease forms that, nonetheless, share three distinguishing characteristics, namely uncontrolled cellular proliferation, invasion of the abnormal cells into adjacent tissues, and their spread to distant organs via blood and lymph vessels . The biological events fundamental to the development of cancer involve the transformation of normal cells to a precancerous lesion which subsequently progresses to a malignant tumor in a multistage process . These changes are the result of the interaction between an individual’s genetic make-up and external agents including physical, chemical, and biological carcinogens .
Recognized physical carcinogens are ultraviolet and ionizing radiation which have been linked to skin cancer as well as leukemia and a number of solid tumors, respectively . Well-studied chemical carcinogens are asbestos that has mainly been associated with lung cancer and mesothelioma; components of tobacco smoke which have been linked not only to breast and lung cancer but also to a host of other malignancies; aflatoxins produced by certain molds in improperly stored staple commodities which have been related to liver cancer; and the drinking water contaminant arsenic that has particularly been associated with lung, bladder, and kidney cancer . Examples of biological carcinogens are the human papillomavirus, the hepatitis B virus, the hepatitis C virus, and the Epstein-Barr virus, the causative factors of cervical cancer, liver cancer, and certain lymphomas, respectively; the stomach bacterium
Molecular insights have revealed that the development of cancer—including its capacity to proliferate in an uncontrolled fashion, escape apoptosis, invade neighboring tissues, and disseminate to distant organs—involves aberrations in molecular networks that include oncogenes, tumor suppressor genes, and repair genes . These changes occur in a multistep manner and often take place over many years . This is an important reason that cancer usually manifests at older age, when sufficient carcinogenic mutations have accumulated to cause cancer and innate defense and cellular repair mechanisms have become less effective .
1.2 Worldwide epidemiology
According to GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, cancer will represent the leading cause of death throughout the world in the twenty-first century . In 2018, there were an estimated 18.1 million new cancer cases and 9.6 million cancer deaths globally . Lung cancer and female breast cancer were the most commonly diagnosed malignancy (each 11.6% of total overall cases), followed by cancer of colon and rectum (10.2%), prostate (7.1%), stomach (5.7%), and liver (4.7%) . The most deadly cancers in that year were lung, colorectal, stomach, liver, and breast cancer accounting for 18.4, 9.2, 8.2, 8.2, and 6.6%, respectively, of the total number of cancer fatalities . The most frequent cancers in males were lung, prostate, colorectal, stomach, and liver cancer with incidence rates of 14.5, 13.5, 10.9, 7.2, and 6.3%, respectively, and mortality rates of 22.0, 6.7, 9.0, 9.5, and 10.2%, respectively . And in females, the most common cancers were those of the breast, colon and rectum, lung, and cervix uteri, with incidence rates of 24.2, 9.5, 8.4, and 6.6%, respectively, and mortality rates of 15.0, 9.5, 13.8, and 7.5%, respectively .
There were substantial variations among countries with respect to the most frequently diagnosed cancers and the leading causes of cancer death . For instance, for many cancers, incidence rates were generally two- to threefold higher in industrialized countries than in transitioning economies . However, differences in mortality were smaller, as relatively more patients in developing countries died from their disease, probably because of low screening rates as well as less advanced screening services and diagnostic methods in these regions . Furthermore, cancers related to a westernized lifestyle such as lung, breast, and colorectal cancer were (much) more common in industrialized regions than in developing/transitioning regions, even though these neoplasms were among the most common malignancies in both regions . On the other hand, oral cancer and cervical cancer were much more frequent in (certain) developing/transitioning countries than in industrialized countries . These differences are probably for an important part attributable to differences in associated risk factors and screening facilities, respectively, resulting in the former malignancy accounting for almost 50% to the burden of cancer in south-central Asia  and the latter occurring at incidence rates between 13.0 and 43.1 per 100,000 in Central America, South America, and the Caribbean, as well as in the parts of Africa .
1.3 Treatment modalities
The treatment modalities for cancer depend on the type of cancer as well as its stage and grade . Some cases require only one form of treatment, but most patients need a combination of therapeutic modalities such as surgery with chemotherapy and/or radiation therapy. Surgery is applied for removing localized solid tumors or debulking large solid tumors in order to improve the efficacy of, for instance, chemotherapy . Radiation therapy—external beam radiation therapy, brachytherapy, or systemic radioisotope therapy—uses high doses of radiation to kill cancer cells by damaging their DNA . Chemotherapy is a systemic treatment with mostly combinations of antineoplastic drugs and is intended to kill cancer cells by stopping or slowing their growth or division, but it is also applied as an adjuvant to prevent disease recurrence after surgery or radiation therapy and as a neoadjuvant therapy to decrease the size of a tumor before surgery or radiation therapy .
Other cancer treatment modalities are immunotherapy, hormonal therapy, and angiosuppressive therapy. Immunotherapy can make use of adoptive cell transfer involving the infusion of engineered autologous or allogeneic T cells into a patient which can attack the cancer directly; monoclonal antibodies directed at cancer cell-specific antigens; or immunomodulating substances such as cytokines and Bacillus Calmette-Guérin vaccine which stimulate the immune system in a more general way . Hormonal therapy slows or stops the growth of hormone-dependent tumors such as breast and prostate cancers, or reduces or prevents the symptoms in patients suffering from these cancers who do not qualify for surgery or radiation therapy . Hormonal therapy can also be used in the adjuvant or neoadjuvant setting . Angiosuppressive or antiangiogenic therapy interrupts the angiogenic signals that a tumor emits to its surroundings for recruiting a blood supply and causes tumors to shrink .
Despite this respectable array of antineoplastic agents and therapeutic modalities most cancers remain fatal, particularly when detected at an advanced stage. This implies a need for more efficacious forms of treatment of neoplastic disease. Many efforts are being dedicated to this goal, including improved early diagnosis, the development of highly specific targeted therapies, and the identification of more efficacious antineoplastic drugs. It is generally agreed that the application of ancient wisdom and folk medicine represents an important strategy to discover and develop new anticancer drugs [7, 8, 9, 10]. This approach has led to breakthrough anticancer drugs such as the tubulin-interfering agents vincristine from the periwinkle plant
So far, only a relative handful of the plant kingdom has been evaluated for pharmacologically active plant substances with potential efficacy against cancer. Therefore, it is likely that further exploration of the rain forests along with other less explored environments such as deserts, tundras, as well as freshwater and marine ecosystems , will help identify many structurally novel and mechanistically unique compounds for fighting cancer. This chapter first reviews a few aspects of cancer throughout the world, then focuses on cancer in the Republic of Suriname, subsequently addresses in detail nine medicinal plants that are used for treating cancer in the country, and concludes with some remarks about their potential usefulness against this disease.
2. Background on Suriname
2.1 Geography, population, demographics, and economy
The Republic of Suriname is situated in the north-eastern part of South America adjacent to the Atlantic Ocean and has a land area of roughly 165,000 km2 (Figure 1). The population of about 570,000 is among the ethnically most varied in the world, comprising Amerindians, the original inhabitants; Maroons, the immediate descendants of enslaved Africans shipped from western Africa between the seventeenth and the nineteenth century; Creoles, a generic term referring to anyone having one or more African ancestors; the descendants from indentured laborers attracted from China, India, and Java (Indonesia) between the second half of the nineteenth century and the first half of the twentieth century; as well as immigrants from various European, South American, and Caribbean countries .
Suriname can be characterized as a demographically transitioning country with declining mortality and infertility rates as well as a growing and aging population. These changes are for an important attributable to considerable progress in health care, nutrition, sanitation, and drinking water quality; the eradication of various infectious diseases; as well as improvements in average living and working conditions, education, and income [17, 18]. The result was a decline of the death rate from 24 per 1000 in 1923 to 6 per 1000 in 2011 and the attainment of an average life expectancy of 70 years in 2011 .
The country’s most important economic means of support are crude oil drilling as well as gold and bauxite mining . These activities, together with agriculture, fisheries, forestry, and ecotourism, have substantially contributed to Suriname’s gross domestic income (GDI) in 2014 of USD 5.21 billion and the average
2.2 Health care
Suriname spends about 5.7% of its GDI—which amounted to USD 589
Primary health care in Suriname is offered by the government-subsidized Regional Health Services and Medical Mission, as well as approximately 250 general practitioners. The Regional Health Services run 43 community health centers staffed with physicians and nurses, covers the entire coastal area, and offers basic laboratory testing as well as curative and preventive services including cervical cancer screening and dental, prenatal, and obstetric care. The Medical Mission is a nongovernmental organization that provides health services to people living in Suriname’s hinterland. The clinics are staffed with community health workers who are supervised by general practitioners who travel back and forth on a regular basis.
Secondary care is provided by two private and two government-supported hospitals in Paramaribo and one public hospital in the western district of Nickerie. Medical emergencies can turn around-the-clock to the First-aid Stations of the Academic Hospital Paramaribo and the Saint Vincentius Hospital Suriname. The Academic Hospital Paramaribo also functions as training facility for both general practitioners and medical specialists. All hospitals have modern clinical laboratory facilities as well as radiology services at their disposal. There are, in addition, four private clinical laboratories and three private radiology clinics. Diagnostic imaging including computed tomography and magnetic resonance imaging is possible at two private clinics and the Academic Hospital Paramaribo. This hospital also provides tertiary care at a Thorax Center, a Neurology High-Care Unit, a Neonatal Care Unit, and a Radiotherapy Center.
3. Cancer in Suriname
As in many other low- and middle-income countries, there is no population-based cancer registry in Suriname. The occurrence of cancer in the country is estimated from data on the histopathologically confirmed cases at the Pathologic Anatomical Laboratory of the Academic Hospital Paramaribo that functions as the country’s cancer-based registry. This institution reported for 2014 a crude incidence rate of 133 per 100,000 population with the most common cancers being breast, colorectal, prostate, and cervical cancer . An earlier publication  mentioned an average of 70 per 100,000 population for the period 1980–2000, suggesting an almost twofold increase in the occurrence of cancer in Suriname since the turn of the century.
Cancer mortality in Suriname has been registered since 1958. In the period between 1962 and 1970, the average death rate due to cancer was 60 per 100,000 per year . This figure had risen to approximately 72 in 2011, ranking cancer as the second most common cause of mortality in the country, after cardiovascular diseases . The top five causes of cancer mortality in that year were prostate, lung, rectum-sigmoid, female breast, and cervical cancer . Most of the fatalities in females were attributable to breast and cervical cancer, while prostate cancer was the leading cause of cancer death in males .
3.2 Allopathic forms of cancer treatment in Suriname
Suriname has no national guidelines for the screening, diagnosis, and treatment of cancer, and structured screening programs for breast, cervical, and colon cancer are nonexistent. For these reasons, a comprehensive national cancer control plan has been developed  that will be executed in the short term by the Ministry of Health.
Still, primary prevention programs such as mandatory vaccination against the hepatitis B virus (since 2011) and the availability of a HPV vaccine for young girls (implemented in 2013) may help reduce the cancer burden in the country. This may also be achieved by early detection services such as screening for cervical and breast cancer, even though these facilities are in general utilized on an
Surgery, radiation therapy, and chemotherapy as standard therapeutic modalities for cancer are all available in Suriname. Surgical treatment is offered by all four hospitals in Paramaribo. Radiation therapy has been available since 2012 and is performed by two radiation oncologists. Chemotherapy is delivered by two oncologists and two gynecologic oncologists. If diagnostic or therapeutic services are not available in Suriname, patients can be transferred to health centers abroad provided that they have a good prognosis and are younger than 70 years. More than half of the selected patients are treated in Bogotá, Columbia. All costs are covered by the Surinamese Ministry of Health through the State Health Foundation .
3.3 Traditional forms of cancer treatment in Suriname
All ethnic groups in Suriname have preserved their own specific identity including their particular forms of traditional medicine, probably as a means of strengthening the ethnic identity after their relocation to their new homeland [27, 28]. Not surprisingly, the use of various traditional medicinal systems—involving, among others, Indigenous, African, and Chinese traditional medicine, Indian Ayurveda, as well as Indonesian Jawa—is deeply rooted in Suriname [27, 28]. Furthermore, Suriname’s large biodiversity provides ample and readily available raw material that can be processed into ethnopharmacological plant-based preparations . As a result, many diseases including cancer are often treated with such medications instead of, or in conjunction with, allopathic forms of treatment  despite the availability of affordable and accessible modern health care throughout the entire country.
This holds true for, for instance, patients who are motivated by aversion of “chemical” drugs with attendant adverse or side effects and those whose philosophy about life is not compatible with the use of allopathic medicine or who have reservations about the viewpoints of allopathic medicine . Others prefer traditional treatments because these modalities would improve conventional therapies and represent gentler means of managing their disease when compared to allopathic medicines . Still other patients, particularly those with advanced disease or cancer that, from a medical standpoint, can no longer be treated, resort to traditional medicines as an ultimate means to improve their situation . And cultural beliefs, traditional values, and certain perceptions of health and disease may entice some people to choose for a familiar traditional therapy rather than a “western” therapy [34, 35].
4. Plants for treating cancer in Suriname
Hereunder, nine plants that are used in Suriname for treating cancer have in detail been assessed for their presumed activity against this disease. The plants have been selected after consulting a number of comprehensive publications describing various aspects of medicinal plants in the country [36, 37, 38, 39, 40, 41, 42, 43]. Several of these plants such as the graviola
|Family||Species (vernacular names in English; Surinamese)||Part(s) used||Active constituent(s)||References|
|Annonaceae||Oil from seed, pericarp, leaf, stembark||Annonaceous acetogenins, terpenes/terpenoids, alkaloids||[47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67]|
|Asteraceae||Whole plant||Sesquiterpene lactones||[74, 75, 76, 77, 78, 79]|
|Asteraceae||Leaf, aerial parts, whole plant||Terthiophenes/thiophenes, saponins, triterpenoids, coumestans, flavonoids||[84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94]|
|Fabaceae||Seed, leaf||Abrin, phenolics, flavonoids||[100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110]|
|Fabaceae||Root, leaf, aerial parts, stem||Benzil derivatives, coumestan derivatives, flavones/flavonoids, phenols||[118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131]|
|Loranthaceae||Whole plant, stem, leaf||Peptides, alkynic fatty acids, lectins, triterpenes, glycosides, flavonoids||[135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148]|
|Rubiaceae||Stembark||Oxindole alkaloids||[157, 158, 159, 160, 161, 162]|
|Simaroubaceae||Stem, leaf||Quassinoids, canthin alkaloids||[171, 172, 173, 174, 175, 176, 177, 178]|
|Zingiberaceae||Rhizome||Gingerols, shogaols||[187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203]|
The sugar apple
The seed oil as well as the essential oils from the pericarp, the leaves, and the stembark of
The antitumor activities have in some cases been associated with cycle arrest effects and apoptotic events [54, 60, 61, 62] as indicated by the increased caspase-3 activity, the downregulation of antiapoptotic genes, and the fragmentation of the nuclear DNA [54, 60]. The mechanism underlying these events presumably involves the generation of oxidative stress . This supposition is based on the enhanced generation of intracellular reactive oxygen species and the decreased levels of intracellular glutathione species noted in cultured human cells undergoing apoptosis following exposure to
Notably, leaf and stembark extracts protected Swiss albino mice and Syrian golden hamsters from the mutagenic effects of the alkylating agent cyclophosphamide  or the potent laboratory carcinogen 7, 12 dimethylbenz(a) anthracene (DMBA) , respectively. Furthermore, aqueous and ethanolic stembark extracts decreased lipid peroxidation and potentiated antioxidant activities in an animal model of oral carcinogenesis . These observations suggest that
Cyanthillium cinereum(L.) H.Rob.
The little ironweed
Pharmacological and phytochemical studies have shown a wide range of bioactive compounds such as (a) sesquiterpene lactone(s), which may lend credit to the traditional uses . Two clinical trials found
Support for anticancer activity of
Other indications for anticancer activity of
Eclipta prostrata(L.) L.
The false daisy
Converging lines of evidence suggest that
Abrus precatoriusL., 1753
The crab’s eye or rosary pea
The sweet-tasting leaves of the plant are used in West Tropical Africa to sweeten foods . These parts of the plant along with the seeds (after denaturing abrin at high temperatures ) are also used in various traditional medicinal systems for treating or preventing tetanus, inflammation, snake bites, rabies, and leukoderma; as aphrodisiacs; as oral contraceptives and abortifacients; and for treating cancer [42, 98].
Pharmacological studies with preparations from
Indeed, protein-rich extracts or peptide fractions from
Importantly, administration of Meth-A tumor cells which had been treated
Tephrosia sinapou(Bucholz) A.Chev.
The Surinam poison
Indications for anticancer activity of
There are also indications for cancer chemopreventive activity of
Phthirusa stelis(L.) Kuijt
The bird vine
None of the parts of the plant have edible uses. However, the viscous layer of its fruits has been suggested to represent a potential source of natural rubber .
Indications for anticancer activity of
Crude extracts from stem or leaves of
Uncaria guianensis(Aubl.) J.F. Gmel.
The cat’s claw
No studies have been carried out on the anticancer activity of
A clinical trial with a dried extract of
The quassinoids quassin, neoquassin, bruceantin, and simalikalactones D and E have been associated with a host of pharmacological activities including antimalarial, insecticidal, anti-inflammatory, antimicrobial, and antianorectic activities [166, 167, 168]. Other
There is ample evidence that
Based on this large body of preclinical data, several
These claims are supported by the pharmacological activities displayed by particularly gingerols (such as zingerone and zingeberol) and shogaols in the rhizomes. Gingerols are the main compounds in the volatile oil of fresh ginger rhizomes and are responsible for their characteristic fragrance . They are thermally labile and easily undergo dehydration reactions to form the corresponding shogaols, which convey the typical pungent taste of dried ginger during cooking . Both gingerols and shogaols exhibited pharmacological activities which supported the traditional uses of
A host of data supports that gingerols and shogaols possess both anticancer and chemopreventive activities. Evidence for the former suggestion came from their inhibitory effects on the proliferation, cell cycle progression, and viability of human carcinoma cell lines [187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197] and tumors implanted into laboratory animal [198, 199]. Suggestions for chemopreventive activities of these compounds came from their inhibitory effects on the development of cancer in animals treated with laboratory carcinogens [199, 200, 201, 202, 203]. Both activities may be mediated by multiple mechanisms including inhibition of invasion through activation of the nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ) ; downregulation of matrix metalloproteinase 9 transcription ; suppression of tumor angiogenesis [191, 194]; deactivation of aberrant cell cycle-regulating elements [189, 200]; and interference with microtubule integrity [190, 196].
All these observations have led to the consideration of
5. Concluding remarks
The nine plants addressed in this chapter have a long traditional use in Suriname against various conditions including neoplastic disease and indeed showed some evidence of anticancer activity. However, in all cases, the evidence was limited to preclinical models and was not sufficient to support claims of clinical efficacy. However, this does not necessarily mean that these plants and their active constituents should be discarded as failed compounds. Some may constitute useful parts of an integrative medical approach for treating or preventing cancer. Others—including many mentioned in this chapter—may boost the immune system or improve overall health, well-being, and quality of life. And still others may help relieve some of the symptoms of cancer such as fatigue or reduce the side effects of chemotherapy and radiotherapy.
Converging lines of evidence lend support to these suppositions. Firstly, several phenolic compounds such as curcumin from the turmeric
Secondly, mistletoe extracts may alleviate cancer-related fatigue ; preparations from the holy basil
Furthermore, recent advances in analytical and computational techniques as well as the introduction of innovative technologies such as predictive computational software may help employ apparently “useless” anticancer compounds in novel ways. For instance, the rejected tubulin-binding maytansines from
Likewise, the therapeutic index of gingerols in the treatment of breast cancer may improve when formulated as a PEGylated nanoliposomal form, allowing for high specificity, improved bioavailability, slow release, and low systemic toxicity . And structural modifications of quassinoids on the basis of, for instance, (quantitative) structure-activity relationships, may produce more potent and less toxic analogues [219, 220]. These and many other examples support continued assessment of the plants and their bioactive compounds dealt with in the current chapter for their usefulness against cancer. If only one of these compounds would reach the clinic, the efforts invested in their evaluation would have been worthwhile.
Conflict of interest
The authors declare that no conflict of interest exists.