In cancer treatment, increase in drug resistance and decrease in new chemotherapeutic drugs have become a pressing problem. Hence, searching for novel anticancer agents with less toxicity and high sensitivity is expanding gradually. Many preclinical and clinical studies indicate that natural antioxidants can help combating carcinogenicity and reduce the adverse effects on cancer therapy, when used alone or as adjuvant in chemotherapy. Consequently, marine algae pave the way for exploring more potential antioxidant compounds which have pharmaceutical importance. Algal terpenoids comprise a large group of bioactive compounds that have excellent antioxidative property and can be used as source of antioxidant in cancer therapy. This chapter summarizes the potential role of terpenoids from algal sources in inhibiting cancer cells, blocking cell cycle, hindering angiogenesis and metastasis as well as in inducing apoptosis.
- algal terpenoids
- marine algae
Though cancer is the prime reason for the premature death and responsible for more than nine million death globally in 2018, cancer treatments are still facing challenges in terms of their potency and safety . Over fifty percent of the existing cancer drugs are from natural origin, therefore, exploration of cancer therapeutics from natural reservoir has been escalated currently . In accordance with this natural anti-cancer drug discovery, natural antioxidants can be considered as an alternative source of cancer therapeutics. Many antioxidants, for instance, vitamins, carotenoids, genistein, curcumin, resveratrol, gingerol etc. exhibited promising outcomes in preclinical and clinical studies . Currently, researchers are looking for more novel phytochemicals that can be further used as cancer drug discovery.
Terpenoids are the broadest class of diverse phytochemicals which are widely available in marine algae. These secondary metabolites have excellent antioxidative property and exerted
2. Role of antioxidant in cancer therapy
Antioxidants are molecules which can detoxify the reactive species (reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), reactive carbonyl species (RCS) and reactive selenium species (RSeS)), that are generated through body’s normal metabolism or can be obtained from environment . These reactive species give rise to oxidative stress which is of two types, oxidative eustress and oxidative distress. Oxidative eustress is considered as good stress, which under basal intensity, maintains redox homeostasis, responsible for controlled cell growth and reversible oxidative modification which ensure normal physiology. On the other hand, oxidative distress is known as bad stress, that in higher intensity, damage biomolecules and consequently disrupt redox signaling and give rise to different diseases, e.g. cancer .
Antioxidants protect cellular damage from free radicles through their organized defense mechanism (Figure 1), where they either inhibit new free radicle formation or scavenge the formed free radicles. They can also repair the damaged DNA and biomolecules . In cancer cells, ROS level is excessively high which helps in pro-tumorigenic cell signaling while prolonging the cell death. Some chemotherapeutic agents also can induce production of high amount of ROS, which is often considered as one of the main reasons for chemotherapeutic treatment side effects. However, antioxidants, when used in therapeutic dose in adjuvant chemotherapy, can hinder this high production of ROS and thus, potentiate the efficacy of cancer treatments, reduce the adverse effects of the therapy and improves the overall health status of the cancer patients. Antioxidants can inhibit cancer proliferation, angiogenesis and metastasis . Dietary antioxidants supplements are frequently in cancer treatment. About 20–80% of the cancer patients use antioxidant supplements after cancer diagnosis . The efficacy of using antioxidants in adjuvant chemotherapy has been assessed in many clinical trials. The clinical studies of antioxidant administration, especially vitamin, glutathione, melatonin, Coenzyme Q10, during chemotherapy have been revealed the reduction of chemotherapy induced toxicity and improvement of patient health .
3. Algal terpenoids as prospective candidate in cancer therapy
Seaweed are more studied, in terms of their terpenoid profile, compared to marine microalgae. Though the anticancer activity of tetraterpenoids from marine microalgae has been reported broadly, brown macroalgae are good source of carotenoids. Anticancer activity of carotenoids (zeaxanthin, lutein, β-carotene, violaxanthin) was reported in Malaysian green and brown macroalgae .
Monoterpenoids, found in different plant parts, like in bark, root, seeds or leaves, have antioxidant and anticancer activity. For instance, carvacrol, thymol, linalool as well as eugenol are good antioxidant and at the same time, exert antitumor activity against liver, prostate and breast cancer cells [13, 14]. Limonene and perillyl alcohol were subjected to phase I clinical trials in cancer patients .
A new diterpenoid has been isolated from green alga
However, diterpenoids can induce apoptosis in cancer cells through downregulating Bcl2 and regulatory pathways like, JAK2/STAT3, PI3K/Akt and NF-κB. They can arrest cell cycle at G1 and G2-M checkpoint. Besides, diterpenoids can also inhibit metastasis and angiogenesis by hindering PI3K/Akt/mTOR and VEGFR-2 signaling pathways .
Triterpenoid (benzene dicarboxylic acid, diisooctyl ester) from the dichloromethane extract of
Algal tetraterpenoids mainly consist of carotenoids, namely, β-carotene, lutein, fucoxanthin, astaxanthin, canthaxanthin, zeaxanthin, cryptoxanthin, violaxanthin, neoxanthin and siphonaxanthin (Figure 2). Theses carotenoids have both antioxidative and anticancer activity with other pharmaceutical importance.
Zeaxanthin separated from
Violaxanthin with antioxidative and anti-inflammatory activities has been isolated from
Siphonaxanthin from green microalgae
Sesquiterpenoids have also high antioxidative and anticancer properties. Green seaweed
The investigation on the anticancer properties of algal terpenoids is still in its infancy, albeit the anticancer efficacy of these phytochemicals is quite persuasive. Marine algae contain a wide array of promising terpenes and terpenoids that can strongly inhibit the proliferation of cancer cells. Extensive research on these algal terpenoids regarding their mechanism of action in the cancer cells and more clinical studies will open the door to develop novel drugs for treating cancer.