Report on Screening of Single Herbal Drug Extracts for Potential Anti-Cancer Activity

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Cancer is defined as any of various malignant neoplasia characterized by the proliferation of anaplastic cells that tend to invade surrounding tissue and metastasize to new body sites. Ayurvedic classics record details on etio-pathogenesis and management of 'Arbuda', a comparable clinical entity to Cancerous conditions. 'Arbuda , stands for malignant type of tumor, which may be compared to the cancer disease. From the population-based registries in India covering 28-30 million populations from different parts of the country, the age adjusted incidence rates vary from 44 to122 per 100,000 population in males and 52 to 128 per 100,000 females. Cancer incidence was higher in females compared to males.

Every year, nearly one million new cancer cases are being detected annually in the country. Cancer is the second most common cause of death in the US, exceeded only by heart disease. It accounts for 1 of every 4 deaths. About 1,437,180 new cancer cases are expected to be diagnosed in 2008. Genetic factors, tobacco, alcohol consumption, infections, food intake contaminated with aflatoxins, dietary habits and behavioral risk factors, etc. are some of the risk factors associated with cancer. Chemicals and internal factors like genetic factors, hormones, immune conditions, and mutations are the other contributing factors.

There are three principal methods of treating cancer viz. Surgery, chemotherapy and radiotherapy. Each of these has its limitations. Ayurvedic treatment with combinations of herbs and minerals can be used as an adjuvant therapy. Plants have an immense potential in improving the quality of life of individuals suffering from various chronic diseases. Ayurvedic therapeutic approaches, such as changes in lifestyle, diet, drugs, panchakarma (body cleansing), exercise, and meditation help to strengthen and purify the body and mind. These holistic treatment procedures not only cure several diseases; but also improve the bodily resistance and rejuvenate the tissues of the body. The Ayurvedic literature describes how this therapy aims to restore a balance of humours (Dosha), bodily tissues (Dhatu) and spirit for good health.

In the modern practice of cancer chemotherapy, several plant derived entities are routinely used as potent cytotoxic agents. These include the Vinca alkaloids, Taxanes, Topotecan and several others which play a vital role in cure of leukaemia, breast cancer, ovarian cancer etc. In the recent years several other plant derived agents are undergoing clinical trials for their anticancer activity. There is a great promise to explore and re-interpret our Ayurvedic Sciences and traditional knowledge using internationally acceptable drug evaluation protocols.

This initiative from CCRAS in which our centre is participating for screening the anticancer activity of some single herbal extracts is an important program aimed to integrate knowledge derived from Ayurvedic sciences for improving modern cancer care.

There is evidence of herbs having been used in the treatment of diseases and for revitalizing body systems in almost all ancient civilizations-the Indian, the Egyptian, the Chinese and even the Greek and Roman civilizations. Plants were the mainstay of medicine and credited with mystical and almost supernatural powers of healing. Plants have a vast potential for their use as a curative medicine. Herbs are used in many different ways. However, the ultimate objective of their use is that they should interact directly with our body chemistry. In the recent time the trend in the research in the filed of cancer is once again shifting towards identifying new medicines for the treatment of cancer from natural products.

In India, the records indicate, that herbs have been in use for treating diseases since ancient times. There are references to the curative properties of some herbs in the Rigveda, which is believed to have been written between 3500 and 1800 BC. Many of the Plants mentioned in the Rigveda can be identified with reasonable certainty, although references to plants in, Rigveda are very sketchy. A more detailed account is found in the Atharuaveda. Fairly comprehensive information about herbs has been recorded in Charaka Samhita and Shusruta Samhita-the two most important works on Ayurvedic system of medicine. The Shusruta Samhita deals with as many as 700 herbs, some of which have not even originated in India. In subsequent years, more and more plants were used in indigenous medicine and their number gradually increased to 1500.

Today there are at least 120 distinct chemical substances derived from plants that are considered as important drugs currently in use in one or more countries in the world. Several of the drugs sold today are synthetic modifications of the naturally obtained substances. Turning to plants and herbs as sources for cancer-fighting drugs is not new. Of the 92 drugs that were approved for cancer treatment from 1983 to 1994, 62 were derived from natural sources. For example, Taxol, isolated from the bark of the Pacific yew tree, is used to treat breast, ovarian, lung, head and neck and bladder cancers. Topotecan, a semi-synthetic derivative of an alkaloid extract from the bark of the Chinese camp to theca acuminate or xi shu tree, is used to treat ovarian and lung cancers. The periwinkle plant yields alkaloids to treat lymphomas, leukemia and several solid tissue tumors. Of the 300,000 land-based plants on earth, less than 5% have been investigated for medicinal use.

Amongst the world's ancient civilization, India has been recognized as a rich repository of natural herbs, which are being used in different indigenous systems of medicines e.g. Ayurveda and, Siddha. Presently there are 9,500 plant herbs used in traditional medicinal systems as well as folk medicines. Terrain and longitudinal position encompassing different climatic zones from arid to temperate region, rainfall zones from highest to lowest ones and phytogeographical regions from rich humid tropics to the alpine vegetation have made India the home for natural herbs. Our rich heritage and mosaic ethnic culture too preserve the diversity of natural herbs widely distributed in different phyto-ecological zones of the country. There is an untapped gold mine of herbs, plants and natural compounds, that may yield less harmful, approved drugs that researchers can validate to bring into the practices in cancer therapy.

This monograph contains the detailed report on anticancer activity of some single herbal standardized extracts against different cancerous cell lines. All the single plant extracts were selected for specific cancer condition based on the classical Ayurvedic literature besides various research reports.

It is my pleasure to honour the pragmatic approach of Dr. Sanjiv Sarin, Director, ACTREC. I appreciate the zeal and efforts of investigators Dr.A.R.Juvekar,Officer-in-charge, Anticancer drug screening facility and Dr.S.M.zingde, Dy.Director of ACTREC. This is the beginning and not end, the study of screening of anticancer herbs will be a ongoing joint venture of CCRAS and ACTREC.

I am pleased to acknowledge the continuous efforts of Council's scientists especially Dr. Sudesh Gaidhani, Assistant Director (Pharmacology), Dr. S.Venugopal Rao Ex. Assistant Director (Pharmacology), Dr.M.M.Padhi, Dy. Director (Tech) and Dr.N.Srikanth, Asstt. Director (Ay.) and Dr. A.D. Jadhav, Research Officer,(Ay.) in successful completion of the work.

**Contents and Sample Pages**