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| Medicinal plants as indispensable source for anticancer phytochemicals | | | Dr VIKAS SHARMA | 6/6/2021 11:56:10 PM |
| Cancer is a group of dis
eases characterized by uncontrolled growth / spread of abnormal cells and is the common cause of death in humans worldwide. It is a multi-gene and multistep disease caused by incorrect diet, genetic predisposition and via the environment, but 95% of all cancers are due to life style and take 20-30 years to develop. Despite of recent developments in the tools of disease diagnosis, cancer is still one of the leading cause of death. The major types of cancer include carcinoma, sarcoma, melanoma, lymphoma and leukemia. Prostate, lung, bronchus, colon, rectum and urinary bladder are the most commonly occurring cancers in men whereas in women most prevalent cancers are breast, lung, bronchus, colon, rectum, uterine corpus and thyroid. This data indicates that prostate and breast cancer constitutes a major portion in men and women respectively. Blood cancer and cancers related to the brain / lymph nodes, commonly occur in children. Both external factors (radiations, smoking, tobacco, pollutants in drinking water, food, air, chemicals, certain metals, infectious agents) and internal factors (genetic mutations, body immune system, hormonal disorders) can cause cancer. In addition, smoking involves several carcinogenic chemical compounds that lead to lung cancer. Interestingly, environmental chemical substances with carcinogenic properties influence directly or indirectly the cytoplasm and nucleus of cells and lead to genetic disorders and gene mutations. Viruses, bacteria and radiation rays are other carcinogenic factors comprising about 7% of all cancers. According to WHO, tobacco has been identified as the major cause of death which ultimately leads to a wide range of cardiovascular / respiratory diseases. Current estimates from the American Cancer Society and from the International Union Against Cancer indicate that 12 million cases of cancer were diagnosed last year with 7 million deaths worldwide and these numbers are expected to double by 2030 (27 million cases with 17 million deaths). According to Indian Council of Medical Research (ICMR), deadly cancer disease has constantly been spreading its tentacles in Jammu and Kashmir during the past several years.
In developed countries the interest in natural products and the use of complementary and alternative medicine is increasing day by day by replacing the use of conventional pharmaceutical approaches. More and more pharmaceutical industries are interested in examining their potential as source of novel medicinal compounds. In the field of anticancer research, natural products has made tremendous achievements i.e., over 60% of clinical use of anti cancer drugs originates from natural sources like plants, marine and microbes. Several active ingredients from natural sources such as alkaloids, flavonoids, terpenoids and saponins are known to possess wide variety of antitumor properties including induction of apoptosis, autophagy and inhibition of cell proliferation. Alkaloids are organic compounds with nitrogen having some biological activity and are mostly present in plants. Vinca alkaloids, isolated from Catharanthus roseus, are the diverse group of phytochemicals employed in several types of cancers like breast, liver, leukemia, testes, lung and the main vinca alkaloids in use are vinorelbine,
vindesine, vincristine and vinblastine. To obtain vincristine, vinblastine is used as a parent drug. Both vincristine and vinblastine bind to a specific site termed as tubulin heterodimers, disrupting the function of microtubules or by arresting cell cycle at metaphase. Taxanes are the promising agents that act by binding to microtubules and play an important role in cell division. Paclitaxel and docetaxel are strong anticancer agents with their efficacy on different molecular targets. Paclitaxel was first isolated from the bark / leaf of Taxus baccata, Taxus canadensis and Corylus avellana and is used for different types of cancers like ovarian, breast, lung. Binding site of paclitaxel is ?-tubulin in the lumen of microtubules decreases microtubules dynamics and thus halt cell cycle at M phase whereas docetaxel from Taxus baccata is used in pancreas, breast, prostate and lung cancer therapies. Camptothecin is clinically active chemotherapeutic agent that possesses strong anticancer potential by inhibiting topoisomerase I. It belongs to a pentacyclic group of quinoline alkaloids, isolated from Camptotheca
acuminata and is mainly present in cortex, wood and fruit part. Production of carboxylic acid derivatives occurs due to hydrolysis of lactone rings present in camptothecin which leads to loss of antitumour activity. It has poor solubility in water, so water soluble semisynthetic derivatives like irinotecan and topotecan were found with clinical application. To overcome the sensitivity of camptothecin to hydrolysis, a methylene group was introduced into their hydroxylactone ring forming a stable seven membered ring which is found to be insensitive to hydrolysis. Second approach used to stabilize
hydroxylactone ring is to replace the lactone ring with five membered keto analogue of the ring thereby retaining high activity against topoisomerase I. Combretastatins is an antiangiogenic agent isolated from Combretum caffrum (African willow) known to suppress tumour angiogenesis. It is a stilbene derivative that exist in both trans (CA-1) and cis (CA-4) forms. Like taxanes and vinca alkaloids, combretastatins are microtubule targetting drugs, belong to a class of vascular disrupting agents, that inhibit the tumour blood vessels and act by binding to ?-tubulin, causing the destabilisation of microtubules. Podophyllotoxin was obtained from Podophyllum peltatum, found in North America, is a toxin lignan.
The constituents present in plant are ?-peltatin, ?-peltatin and their corresponding glycosides, along with podophyllotoxin ?-D-glucoside. Podophyllotoxin and its derivatives are aryl tetralin lactone compounds with lactone ring in trans confirmation. They exhibit significant biological activity as antiviral agents and as antineoplastic drugs. Colchicine, a natural bioactive compound isolated from Colchium autumnale is an alkaloid used to treat various diseases like crystal arthritis, cirrhosis, gout etc. It act by binding to tubulin, stabilizes microtubule formation, arrest cell cycle at different phases and induces apoptosis, but surprisingly, its action is not very specific as it target rapidly dividing normal cells and arrest their cell cycle. So, semisynthetic deriatives like colchicinamide, deacetylcochicine have been developed with lower toxicity and used for treatment of variety of cancers.
Therefore, medicinal plants are known to help humans for better health, a source of active ingredients with major role in infectious diseases and tumour therapy. Several medicinal plant species and their phytochemicals inhibit the progression and further development of cancer. Consumption of plant derived medicines is wide spread and increasing significantly in both traditional and modern medicine. Different parts of a plant may possess different level of pharmacological activity. Additive or synergistic effects of bioactive
phytoconstituents might be responsible for the concerned pharmacological function rather than the purified one. According to the World Health Organization, more than 80% of the world population in developing countries depends primarily on plant based medicines for basic healthcare needs.
The author is Assistant Professor, Division of Biochemistry, FBSc., SKUAST-JAMMU
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