Anticancer Activity and Evaluation of Radio Protective Potential of Medicinally Important in Indian Bamboo Plants

Cancer, a pathological condition characterized by the rapid, abnormal, uncontrolled and proliferative growth of body cells, is the world's most feared causes of morbidity and mortality, claiming about 8.8 million lives in 2015 alone. It contributes 16% to global deaths, making it the second most deadly disease after cardio-vascular diseases, with 32% of total deaths (1). Despite the enormous advances in medical research, complete treatment of an advanced stage of cancer is still elusive, a problem aggravated by late diagnosis of several cancer types. Further, apart from the obvious physical and psychological sufferings any new cancer diagnosis unleashes on patients and their family and friends alike, there is also a huge economic predicament associated with cancer treatment which is particularly harsh for less resourceful and economically weaker sections of society. It was calculated that the total annual economic burden of cancer was staggering US$ 1.16 trillion, and most of this expense was incurred in care alone. This cancer's social and economic burden can be minimized to a bare minimum if we can focus our efforts and money more on stopping the cancer at its onset, i.e. prevention rather than care. It was estimated that about 30-50 percent of all cancer-related deaths were preventable as they were caused by various behavioral and dietary hazards, with the most notable being a poor dietary consumption of fruits and vegetables (2,3). Chemotherapy is widely used in the treatment of cancer. Since cancer cells lack many of the regulatory roles in normal cells, while normal cells do not, they continue to divide. This feature makes chemotherapeutic medication sensitive to cancer cells. Approximately five decades of discovery and production of systemic drugs have resulted in a large number of useful chemotherapy agents being developed. Chemotherapy treatments, however, are not devoid of their own inherent problems. Different types of toxicity may occur as a result of chemotherapeutic treatments The toxicity of chemotherapeutic drugs sometimes creates a significant problem with allopathy or established medicine in the treatment of cancer. Various therapies have been propounded for the treatment of cancer, many of which use plant-derived products. There are currently on the market four groups of plant-derived anticancer agents, vinca alkaloids (vinblastine, vincristine and vindesine), epipodophyllotoxins (etoposide and teniposide), taxans (paclitaxel and docetaxel) and camptothecin derivatives (camptotecin and irinotecan). Plants still have enormous potential to supply new drugs and as such are a source of natural chemicals that can provide fuel for chemoprotection against cancer. A variety of compounds from medicinal plants with possible anti-cancer activities have recently been suggested by Taneja and Qazi (4).

evergreen plant belonging to the Bambusoideae subfamily under the monocotyledonous Poaceae family, has a well-developed underground rhizome system with vegetative buds rising outward to form aerial culms. These bamboo shoots are called these developing, actively growing and tender culms.

Components of edible plant foods, which are mostly non-digestible in human gastrointestinal tract and are either water soluble or insoluble, have traditionally been referred to as dietary fibre collectively and include polysaccharides such as cellulose, hemicellulose, pectin, gums, mucilages and lignin

Phenols include a large group of diversified secondary metabolites developed primarily through pathways of shikimate, phenylpropanoid, flavonoid, anthocyanin, and lignin. Both phenols are structurally simple aromatic hydrocarbons with either one (phenol) or more than one hydroxyl group (polyphenols) substitution. The major group of plant phenolic compounds comprises flavonoids (flavones, flavonols, anthocyinidin, isoflavones, etc.); tannins; chalcons; coumarins and phenolic acids (12). Phenolic compounds are the largest groups of natural antioxidants, primarily due to the good hydrogen-donating properties of their hydroxyl groups. We avoid the oxidative damage to specific biomolecules such as DNA, lipids and proteins by scavenging different reactive species such as radical superoxide, hydroxyl radical, peroxyl radical, chypochloric acid and peroxynitrous acid and chelating metal ions, thereby playing an important role in the prevention of various chronic diseases such as cardiovascular diseases, gastric ulcers, (13,14,15). their strong anti-oxidant existence. Several epidemiological studies have confirmed that phenols have a positive effect on several types of cancer reduction. In a prospective study involving 9959 men and women in Finland, Knekt et al. (1997) found an inverse relationship between flavonoid intake and cancer incidence with a decrease of up to 50 percent in lung cancer development following the maximum intake of flavonoids. Consumption of quercetin extracted from onions and apples was found to be beneficial against lung cancer and squamous-cell carcinoma (Marchand et al. 2000; Boyle et al. 2000).

MEDICINAL PLANTS AND CANCER

For decades, plant anticancer properties have been known. The isolation of podophyllotoxin from the common mayapple (Podophyllum peltatum) and several other compounds (known as lignans) eventually led to the development of drugs for the treatment of testicular and small cell lung cancer (5). About 35,000 plant species have been tested for possible anticancer behaviors by the National Cancer Institute (NCI). About 3,000 plant species have shown reproductive activity against cancer Cancer is one of the world's most severe health issues in both developing and developed countries. Lung cancer has continued to be the most common type of cancer diagnosed in men (lung, stomach, colorectal, liver, breast) and the most common cancer diagnosed in women. An estimated 12.7 million people worldwide have been diagnosed with cancer (6). Among low-and middle-income countries, more than 70% of all cancer deaths occurred. Deaths from cancer are projected to continue to grow, with an estimated 11.5 million deaths in 2030 (7) and 27 million new cancer cases and 17.5 million deaths from cancer predicted to occur worldwide by 2050 (8.9). More than 30% of cancers are caused by modifiable behavioral and environmental risk factors, including tobacco and alcohol use, dietary factors, insufficient regular consumption of fruit and vegetable, overweight and obesity, physical inactivity, chronic infections from Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV) and some types of human papilloma virus (HPV), environmental and occupational risks including exposure to ionizing and nonionizing. Ayurveda, a traditional Indian medical practice using plant drugs has been successful from very early times in using these natural drugs and preventing or suppressing various tumours with different lines of treatment (10). In India, people of different ethnic groups inhabiting various terrains, possess their own distinct culture, religious rites, food habit and a rich knowledge of traditional medicine (11). They practice herbal medicine to cure a variety of been used in the treatment of various diseases for thousands of years. Terrestrial plants have been used as medicines in Egypt, China, India and Greece from ancient times and an impressive number of modern drugs have been developed from them. Conventional treatment of cancer includes interventions such as psychosocial support, surgery, radiotherapy and chemotherapy. Currently, the most commonly use cancer chemotherapy includes mainly alkylating agents, antimetabolites, antitumor antibiotics, platinum analogs and natural anticancer agents (12). However, due to the increasing rate of mortality associated with cancer and adverse or toxic side effects of cancer chemotherapy and radiation therapy, discovery of new anticancer agents derived from nature, especially plants, is currently under investigation. Screening of medicinal plants as a source of anticancer agents was started in the 1950s, with the discovery and development of vinca alkaloids, vinblastine and vincristine and the isolation of the cytotoxic podophyllotoxins (1). Amarkantak, chhindwara and Panchmari Madhya Pradesh India's cool temperate climate promotes the growth of a huge number of plant species that are important sources of unique anti-cancer phytochemicals. Selected medicinal plants grown in Amarkantak chhindwara (Patalkot) and Panchmari's cool climate are discussed in this section. The major bioactive phytochemicals and their mechanisms of action are also reviewed. Rubia cordifolia is a flowering plant with red rhizomatous base and roots, a member of Rubiaceae family, distributed in hilly tracts of India. It has been stated in literature that the powdered dried roots and fruits have been studied for the treatment of skin diseases and spleen disorders and their preparations are used for the treatment of severe burns, bone fractures and dysentery and are considered to be tonic, antitussive and useful for chronic low fevers (Dev, 2006). This plant has many pharmacological properties such as blood purifier activity, anticancer, astringent, antidysentric, antiseptic, hepatoprotective, antirheumatic, etc. R. Cordifolia has been reported to be involved in a number of cancer cell lines such as P388, L1210, L5178Y, B16 melanoma, Lewis lung carcinoma, and sarcoma-180. Rubia cordifolia L's roots showed strong cytotoxicity against cell linesHT-29andMCF-7, and inhibitory activities of DNA topoisomerase I and II. The adverse effects of oxidative stress have become a serious problem for human health. The World Health Organization (WHO) has reported that 80 percent of the world's inhabitants rely on traditional medicine for their primary health care needs, and most of this therapy requires the use of plant extracts and their active components. Medicinal plants have great antioxidant potential which is due to their contents of variable phyto constituents. A large number of experiments activity of several plant extracts and powders(13).

Tinospora cordifolia, also known as Sanskrit guduchi, Hindi giloya and English heartleaf moonseed plant, is a large, smooth, climbing deciduous shrub with no bristles. The stem is the most widely used component of the shrub, but essential alkaloids are also known to contain roots. Throughout India, Myanmar, Sri Lanka and China, this shrub is commonly found.

Ziziphus nummularia, also known as bhukamtaka sukhsharanphala in Sanskrit, Hindi harbor and English wild jujube, is a thorny little bush or divaricating shrub with palepurple stems and or pairs of gray-velvety stipulated prickles. Root, bark, stem, flowers and seeds are the various parts of the plant used for medicinal purposes. In India, Pakistan, Afghanistan, Egypt, Iran, Iraq, and Israel, this shrub is generally found.

Schumach, Phyllanthus amarus. & Thonn Phyllanthus amarus is found in tropical Asia, especially in warmer parts of India. It is known as Sanskrit bhumyamalaki, Hindi jaramla and English stone breaker. It is claimed that the entire plant, leaves, roots and shoots are used for their medicinal values. P. amarus contains various lignans, flavanoids and tannins, and there is evidence that P. amarus extract may have antitumor effects. (15) Oral administration of P. amarus extract significantly increased the life span and reduced tumor size in mice bearing Dalton‘s lymphoma ascites (DLA) and Erlich ascites carcinoma (EAC) [15]. The chemoprotective properties of this plant may be related to its ability to inhibit metabolic activation of carcinogenic compounds, induce cell cycle arrest and interfere with DNA repair(16). P. amarus plant

marker enzymes and liver injury markers has been reported. P. amarus extract has been shown to inhibit DNA polymerase of hepatitis B virus and related hepatitis viruses and down regulates hepatitis B virus mRNA transcription and translation.

According to ancient Ayurvedic lexicons, T. cordifolia is also referred to as ―amrita‖. The term ―amrita‖ is ascribed to this plant due to its ability to impart youthfulness, vitality and longevity. The stem of T. cordifolia is used for general debility, dyspepsia, fever, urinary disease, and jaundice [18]. The extract of its stem is used in treating skin diseases [19]. There are certain curative properties of the root of T. cordifolia which allow for its use as antidote in snake bite, in combination with other drugs [20, 21]. T. cordifolia is well known in modern medicine for its adaptogenic, immunomodulatory and anti-oxidant activities [22]. T. cordifolia is also known to have anti-inflammatory, anti-arthritic, anti-allergic properties. This plant is also useful in treating skin diseases, vomiting, anemia, piles, chronic fever, and emaciation. The methanol extract of Tinospora contains phenylpropanoids, norditerpene furan glycosides, diterpene furan glycosides and phytoecdysones. The roots of T. cordifolia are also reported to contain other alkaloids like choline, tinosporin, columbin, isocolumbin, palmatine, tetrahydropalmatine and magnoflorine Betulin and betulinic acid (chemical structures shown on next page) are present within the bark and stem of Z. nummularia and have been shown to have antitumor activity [23]. Betulinic acid glycosides produce differential cytotoxicity, such that cancer cell lines are more sensitive than normal cells [24]. acid has been suggested to induce apoptosis by generation of reactive oxygen species, inhibition of topoisomerase I, activation of the mitogen activated protein kinase (MAP kinase) cascade, inhibition of angiogenesis, and modulation of pro-growth transcriptional activators and aminopeptidase-N activity [25]. Furthermore, betulinic acid has been shown to induce apoptosis by a p53- and CD95-independent mechanism [25]. These mechanisms may be responsible for the ability of betulinic acid to effectively kill cancer cells that are resistant to other chemotherapeutic agents [25]. Alcoholic extract of A. paniculata has been shown to cause a significant increase in the activities of glutathione-S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD) and catalase, differentially in the lung, liver, kidney and forestomach [26]. It also causes a decrease in the activity of lacate dehydrogenase (LDH) and malondialdehyde (MDA) [26]. Andrographis also results in alterations in the level of glutathione (GSH) [26], and GSH significantly contributes to its function of detoxifying the xenobiotics which may play a causative role in the carcinogenic process [27]. A major chemical constituent of A. paniculata, andrographolide has also shown significant anticancer and immunostimulatory activities. The in vivo results conducted in immuno-competent Swiss albino mice, demonstrated that andrographolide significantly inhibits the cancer cell proliferation without showing any signs of toxicity in mice, even at relatively high doses [28].

The purpose of this study was to provide an overview of the progress of medicinal plant anticancer research across Continental India, focusing on scientists ' most significant findings in this area. We tried to explore the discovered components of plants with proven in vitro and in vivo anticancer activity. India is one of the most exciting regions for the discovery from its flora of new biologically active substances. Further efforts are required to explore powerful Mother Earth anticancer plants and save people from cancer around the world. The purpose of this study was to provide an overview of the progress of medicinal plant anticancer research across Continental India, focusing on scientists ' most significant findings in this area. We tried to explore the discovered components of plants with proven in vitro and in vivo anticancer activity. India is one of the most promising regions for the discovery from its flora of novel biologically active substances. More effort is needed to explore strong anticancer plants from the world.

1. WHO (World Health Organization), 2013. Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013-2020. 2. Doll, R. & Peto, R. (1981). The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. JNCI: Journal of the National Cancer Institute, 66(6), pp. 1192-1308. 3. Stewart, B.W. & Wild, C.P. (2014). World cancer report 2014. International Agency for Research on Cancer, Lyon CEDEX, France. 4. Taneja, S.C. & Qazi, G.N. (2007). Bioactive Molecues in Medicinal Plants: A perspective in their therapeutic action, in Drug discovery and development. Chorghade, MS., editor. John Wiley and Sons, Inc;. pp. 1-50. 5. Pettit G.R., Tan R., Ichihara Y., Williams M.D., Doubek D.L., Tackett L.P., Schmidt J.M., Cerny R.L., Boyd M.R., Hooper J.N. (1995). J. Nat. Prod.; 58(6): pp. 961–965. [PubMed: 7673945] 6. Cancer Research UK and International Agency for Research on Cancer, Cancerstats, Cancer Worldwide. 2011. 7. Russo, A., Piovano, M., Clericuzio, M., Lombardo, L., Tabasso, S., Chamy, M.C., Vidari, G., Cardile, V., VitaFinzi, P., Garbarino, J.A. (2006). Putrescine-1,4-dicinnamide from Pholiota spumosa (Basidiomycetes) inhibits cell growth of human prostate cancer cells. Phytomed., 14(2-3): pp. 185- 91. 8. Douglas Kinghorn, A. (2015). Review of Anticancer Agents from Natural Products J. Nat. Prod., 78(9), pp. 2315– 2315. DOI: 10.1021/acs.jnatprod.5b00617 Publication Date (Web): September 10, 2015. 9. Xiaoli Xu, Yue Wu, Mingyang Hu, Xiang L, Congying Gu, Qidong You, Xiaojin Zhang (2016). Structure–activity relationship of Garcinia xanthones analogues: Potent Hsp90 inhibitors with cytotoxicity and antiangiogenesis activity Bioorganic & Medicinal Chemistry, 24(19): pp. 4626-4635. 10. Balachandran, P. & Govindarajan, R. (2005). Cancer- an ayurvedic perspective. Pharmacol. Res., 51: pp. 19-30. Lee, et. al. (2006). DNA Topoisomerases I and II Inhibition and Cytotoxicity of Constituents from the Roots of Rubia cordifolia, Bull. Korean Chem. Soc., 27: pp. 8. 12. Rahman, H.S., Rasedee, A., Yeap, S.K., Othman, H.H., Chartrand, M.S., et. al. (2014). Biomedical properties of a natural dietary plant metabolite, Zerumbone, in cancer therapy and chemoprevention trials. BioMed. Res., pp. 1-20. 13. Marzouk, M.S.A., Moharram, F.A., Mohamed, M.A., Gamal-Eldeen, A.M. and Aboutabl, E.A. (2006). Anticancer and antioxidant tannins from Pimenta dioica leaves. J. Biosci., 62: 526-536 14. Siripong P., Preechanukool K., Picha P., Tunsuwan K., Taylor W.C. (1992). J. Sci. Soc. (Thailand).; 18: pp. 187–194 15. Rajeshkumar N.V., Joy K.L., Kuttan G., Ramsewak R.S., Nair M.G., Kuttan R. (2002). J. Ethnopharmacol; 81(1): pp. 17–22. [PubMed: 12020923] 94. Jeena KJ, Kuttan R. Cancer Lett. 1999; 136:1 16. Huang S., Lee P., Yang S., Liao S., Chen T., Pang J. (2006). Int. Immunopharmacol; 6(6): pp. 870–879. [PubMed: 16644472] 17. Leite D., Kassuya C., Mazzuco T., Silvestre A., de Melo L., Rehder V., Rumjanek V., Calixto J. (2006). Planta Med.; 15: pp. 1353–1358. [PubMed: 17054045] 18. Singh S.S., Srivastava S., Gupta V.S., Patro B., Ghosh A.C. (2003). Ind. J. Pharmacol.; 35: pp. 83–91. 19. Diwanay S., Chitre D., Patwardhan B. (2004). J. Ethnopharmacol.; 90(1): pp. 49–55. [PubMed: 14698508] 20. Nadkarni, K.M.; Nadkarni, A.K. (1976). Indian Materia medica. 3rd edition ed. Vol. Vol. 1. Bombay: Popular Prakashan Pvt. Ltd; pp. 1220-1221. 21. Zhao T.F., Wang X.K., Rimando A.M., Che C.T. (1991). Planta Med.; 57(5): pp. 505. [PubMed: 1798808] 22. Sarek J., Kvasnica M., Urban M., Klinot J., Hajduch M. (2005). Bioorg. Med. Chem. Lett.; 15(19): pp. 4196–4200. [PubMed: 16051489]

16787747]

24. Eiznhamer D.A. & Xu Z.Q. (2004). Drugs; 7(4): pp. 359–373. 25. Singh R.P., Bannerjee S., Rao A. (2001). Phytother. Res.; 15: pp. 382–390. [PubMed: 11507728] 26. Meister A. (1994). J. Biol. Chem.; 269(13): pp. 9397–9400. [PubMed: 8144521] 27. Ajaya K.R., Sridevi K., Vijaya K.N., Nanduri S., Rajagopal S. J. (2004). Ethnopharmacol.; 92(2,3): pp. 291– 295. [PubMed: 15138014]

Research Scholar, Jiwaji University, Gwalior