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1. INTRODUCTION

1.1. Medicinal Plants

Medicinal plants are the large group of plants used in different systems of medicine for

therapeutic or prophylactic purposes. From the ancient ages humans use medicinal plants

as a source of drugs and nutritive values which are well documented different Indian and

other traditional systems of medicine. Natural products derived from the plants, animals

and mineral sources are the basis for the modern medicine and allopathic systems also

inspires to discover and synthesize new chemical entities to cure diseases (Gupta, 1994).

A huge collection of promising lead molecules were isolated from medicinal plants

include Vinka alkaloids for cancer, Quinine and Artemether for malaria, Holarrhena

alkaloids for amoebiasis, Guggulsterons as hypolipidemic agents, Mucuna pruriens for

Parkinson‘s disease, piperidines as bioavailability enhancers, baccosides for mental

retention, picrosides for hepatic protection, phyllanthins as antivirals, curcumines for

inflammation, withanolides and many other steroidal lactones and glycosides as

immunomodulators (Mukherjee et al., 2010). It is difficult to imagine the world without

medicinal plants because; the general public has increased their use of alternative

medicine and has turned to herbal remedies as one of the major systems for preventative

medicine and as a form of self-care. It has been estimated that approximately 80% of the

population in developing countries depend on medicinal plants for their primary health

care (Kirby, 1996; Hostettman and Marston, 2002). In China, traditional herbal

preparations account for 30 to 50% of the medicines consumed.

1.2. Role of Ethnopharmacology in Drug discovery

Ethnopharmacology is study of the interdisciplinary scientific exploration of biologically

active agents traditionally employed or observed by man. Ethnopharmacology is a highly

diversified approach to drug discovery involving the observation, description, and

experimental investigation of indigenous drugs and their biologic activities. It is based on

botany, chemistry, biochemistry, pharmacology, and many other disciplines

(anthropology, archaeology, history, and linguistics) that contribute to the discovery of

natural products with biologic activity (Daniel and Norman, 2001). This plant based

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traditional system can offer a more holistic approach in drug discovery process to find

more promising lead compounds for existing diseases. Many researchers emphasized that

ethanopharmacological approach can reduce the cost and time taken to discover the novel

drugs. The advantages of doing drug development based on ethnopharmacology,

therefore, are manifold: 1) plant selection 2) "leads" from traditional use that allow for

narrowing the pharmacological study. 3) leads from traditional modes of preparation that

provide clues to active chemical compounds 4) lower laboratory investments altogether

these advantages could shorten the research/productivity cycle - currently estimated at 20

years. Now days it is estimated costs for developing new drugs based on chemical

synthesis and/or mass screening range from US $50 million to $200millioon, If a industry

choose to produce novel drugs from plant products based on ethnopharmacology can

reduce the R&D cost of Drug development dramatically (Elaine, 1991).

Despite the small number of species sources explored yet, drugs derived from plants are

of immense importance in terms of numbers of patients treated. It is reported that 25% of

all prescriptions dispensed from community pharmacies in the USA between 1959 and

1973 contained one or more ingredients derived from higher plants (Farnsworth and

Soejarto, 1991). A more recent study, of the top 150 proprietary drugs used in the USA in

1993, found that 57% of all prescriptions contained at least one major active compound

currently or once derived from (or patterned after) compounds derived from biological

diversity (Grifo and Rosenthal, 1997). Financially, the retail sales of pharmaceutical

products were estimated at US$ 80-90 billion globally in 1997, with medicinal plants

contributing very significantly. A study of the 25 best-selling pharmaceutical drugs in

1997 found that 11 of them (42%) were biologicals, natural products or entities derived

from natural products, with a total value of US$ 17.5 billion. The total sales value of

drugs (such as Taxol) derived from just one plant species (Taxus baccata) was US$ 2.3

billion in 2000 (Bhushan, 2007) (Table 1).

1.3. Ethnomedicine practice in India

In India, medicinal and aromatic plants have been in use in one form or another, under

indigenous systems of medicine like Ayurveda, Siddha and Unani etc. India is having a

well-recorded and well practiced knowledge of traditional herbal medicine. India is one

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of the 12 mega biodiversity centres having over 45,000 plant species. The country has

15,000–18,000 flowering plants, 23,000 fungi, 2500 algae, 1600 lichens, 1800

bryophytes and 30 million micro-organisms; among them 5000 species of plants were

reported in classic ancient texts to use in 25,000 of formulations to cure various disorders

(Drugs and Pharmaceuticals, 1998).

In India, the traditional folklore healthcare system has a long history and is very deeply

rooted in rural and tribal populations. The 550 tribal communities, belonging to 277

ethnic groups, present perhaps the richest heritage of India. They account for about 7% of

the population in India. A survey of the use of plants that the tribal communities make

came out with staggering data of diversity. According to a recent study conducted under

All India Co-ordinated Project on Ethnobiology (AICRPE)- (1992-1998),over 10,000

wild plant species are reported to be used by tribals for meeting their primary healthcare,

food and other material requirements (AICRPE, 1992) . They use over 3,900 species of

plants 6 for edible purposes, over 8,000 for medicinal uses, another 1,000 for fodder,

fibre and assorted purposes. Tribal healers are known to use their own systems of

healthcare with plant and animal extracts, faith and mystical rituals (Pushpangadan,

2003).

The major traditional sector pharmas, namely Himalaya, Zandu, Dabur, Hamdard,

Maharishi, etc. and modern sector pharmas, namely Ranbaxy, Lupin, Allembic, etc. are

standardizing their herbal formulations by chromatography techniques like TLC/HPLC

finger printing, etc. There are about 7000 firms in the small-scale sector manufacturing

traditional medicines with or without standardization. In view of the potentiality in the

traditional medicine, history of long usage among masses it has attracted the attention of

world over to rediscover Ethnomedicine as alternative to modern medicine. In developing

country like ours, with rich heritage in traditional practices and scientific exploration of

these traditional medicines can provide better health care needs with low cost medicines

to the people of India.

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Table1. Drugs derived from plants, with their ethnomedical correlations

and sources (Bhushan, 2007)

Drug Action or clinical use Plant source

Acetyldigoxin Cardiotonic Digitalis lanata Ehrh.

Adoniside Cardiotonic Adonis vernalis L.

Ajmalicine Circulatory disorders Rauvolfia serpentina (L.) Benth

Bergenin Antitussive Ardisia japonica Bl.

Bromelain Anti-inflammatory; proteolytic

agent Ananas comosus (L.) Merrill

Caffeine CNS stimulant Camellia sinensis (L.) Kuntze

Colchicine Antitumor agent; antigout Colchicum autumnale L

Digitalin Cardiotonic Digitalis purpurea

Etoposide Antitumour agent Podophyllum peltatum L.

Glaucaroubin Amoebicide Simarouba glauca DC.

Glycyrrhizin Sweetener Glycyrrhiza glabra

Morphine Analgesic Papaver somniferum L.

Noscapine. Antitussive Papaver somniferum L

Papain Proteolytic; mucolytic Carica papaya L

Pilocarpine Parasympathomimetic Pilocarpus jaborandi Holmes

Quinine Antimalarial Cinchona ledgeriana Moens

Quisqualic Acid Anthelmintic Quisqualis indica L.

Reserpine Antihypertensive; tranqulizer Rauvolfia serpentina (L.) Benth

ex. Kurz

Rhomitoxin Antihypertensive Rhododendron molle G. Don

Sennosides A & B Laxative Cassia spp.

Silymarin Antihepatotoxic Silybum marianum (L.) Gaertn

Teniposide Antitumor agent. Podophyllum peltatum L

Tubocurarine Skeletal muscle relaxant Chondodendron tomentosum R.

Vincamine. Cerebral stimulant Vinca minor L.

Xanthotoxin Leukoderma; vitiligo Ammi majus L

Yohimbine Aphrodisiac Pausinystalia yohimbe

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1.4. Cancer

Cancer is the name for a group of more than 100 diseases in which cells in a part of the

body begin to grow out of control. Although there are many kinds of cancer, they all start

because abnormal cells grow out of control. Untreated cancers can cause serious illness

and even death.

Tumor is mass of tissue formed as result of abnormal, uncoordinated and uncontrolled

proliferation of cells. It is commonly used as a synonym for a neoplasm. Tumors are two

types they are: benign ‗when they are slow growing and localize without causing much

difficulty to the host or malignant ‗when they proliferate rapidly, spread throughout the

body and may eventually cause death of the host. The common term used for all

malignant tumors are ―cancer‖ (Mohan, 2005).

1.5. About cancer facts

Cancer is a leading cause of death worldwide: it accounted for 7.9 million deaths

(around 13% of all deaths) in 2008.

Lung, stomach, liver, colon and breast cancer cause the most cancer deaths each

year.

The most frequent types of cancer differ between men and women.

About 30% of cancer deaths can be prevented.

Tobacco use is the single most important risk factor for cancer.

Cancer arises from a change in one single cell. The change may be started by

external agents and inherited genetic factors.

About 72% of all cancer deaths in 2007 occurred in low and middle income

countries.

Deaths from cancer worldwide are projected to continue rising, with an estimated

12 million deaths in 2030.

1.6. Epidemiology

World health organization (WHO) annually produces the health statistics from WHO‘s

193 member states. The most recent health statistics was published in the world health

statistics 2007.

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Figure 1: Projected global deaths for selected causes of death, 2002-2030.

According to the published graph (Figure 1) in early 2006 by Mathers and Loncar 34 the

causes of global death during 2002-2030 were statistically predicted and estimated. The

predicted graph was expressed in the world health statistics 2007. The world will

experience a substantial shift in the distribution of deaths from communicable diseases to

non-communicable diseases during the next 25 years, with the expansion of HIV/AIDS.

Overall, non-communicable diseases will account for almost 70% of the deaths in 2030.

The first three leading causes of death globally in 2030 are projected to be cancer,

ischemic heart disease and cerebrovascular disease (stroke) (WHO Press 2008). From a

total of 58 million deaths worldwide in 2006, cancer accounted for 7.6 million (13%) of

all deaths. More than 70% of all cancer deaths in 2006 occurred in low and middle

income countries. The main type of cancer leading to overall cancer mortality were lung

(1.3 million deaths/year), stomach (1 million deaths/year), liver (0.662 million

deaths/year), colorectal (0.655 million deaths/year) and breast (0.502 million

deaths/year). Death from cancer in the world is projected to continue rising, it was

estimated that 9 million people will die from cancer in 2015 and 11.4 million will die in

2030.

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Cancer Mortality in India

A nationally representative cancer survey stating the statistics of deaths of cancer in India

as follows, 7137 of 122 429 study deaths were due to cancer, corresponding to 556 400

national cancer deaths in Indiain 2010. 395 400 (71%) cancer deaths occurred in people

aged 30–69 years (200 100 men and 195 300 women). At 30–69 years, the three most

common fatal cancers were oral (including lip and pharynx, 45 800 [22·9%]), stomach

(25 200 [12·6%]), and lung (including trachea and larynx, 22 900 [11·4%]) in men, and

cervical (33 400 [17·1%]), stomach (27 500 [14·1%]), and breast (19 900 [10·2%]) in

women. Tobacco-related cancers represented 42·0% (84 000) of male and 18·3% (35

700) of female cancer deaths and there were twice as many deaths from oral cancers as

lung cancers (Dikshit et al, 2012).

1.7. Molecular biology of cancer

The accumulation of abnormal genes in uncontrollable cancer cells affects the cell

regulatory mechanisms. This is reflected in several aspects cell behaviors that distinguish

cancer cells from their normal counterparts in term of cell size, shape, number,

differentiation and function. The vast catalogue of cancer cell genotypes is a

manifestation of six essential alterations in cell physiology that collectively dictate

malignant growth (Hanahan and Weinberg, 2000):

a) Self-sufficiency in growth signals

b) Insensitivity to growth-inhibitory signals

c) Evasion of programmed cell death

d) Limitless proliferation

e) Formation of new blood vessels

f) Tissue invasion and metastasis

The uncontrolled proliferative behavior of cancer cells in vivo is mimicked in in- vitro

cell culture. A primary distinction between cancer cells and normal cells in culture is that

normal cells proliferate until they reach a finite cell density and then become quiescent,

arrested in the G0 stage of cell cycle. While cancer cell proliferation is not sensitive to

density-dependent inhibition and loose the contact inhibition of cell-cell interactions

simultaneously (Koolman and Rohm, 1996).

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Therefore, they continue to migrate over adjacent cells and grow in multilayered pattern.

The unlimited proliferation of cancer cells results from the decrease of growth factor

requirements due to they can produce their own growth factors that can lead to

continuous auto-stimulation of cell division.

Two additional properties of cancer cells affect their interactions with other tissue

components, which display important roles in invasive and metastasis. First, cancer cells

secrete metalloproteases that digest extracellular matrix components, allowing the cancer

cells penetrate through basal lamina to invade underlying connective tissue. Second,

cancer cell secrete growth factors that promote the formation of new blood vessels

(angiogenesis) when the size of the tumor tissue is formed of about a million cells to

supply oxygen and nutrient to the proliferating cancer cells. In addition, angiogenesis

provide a ready opportunity for cancer cells to enter the circulatory system and begin the

metastatic process (Cooper, 2000). Although a large amount of adequate nutrient is

supplied, cancer cells are usually blocked at an early stage of differentiation and fail to

undergo terminal differentiation. Instead, they become arrested at early stages of

maturation at which they retain their capacity for proliferation and continue to reproduce

(Figure 3).

Figure 2: The development of cancer

Coincident with their failure to differentiate normally, many cancer cells fails to undergo

apoptosis and therefore exhibit increased life span compared to their normal counterparts.

These failures to differentiate and undergo programmed cell death contribute

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substantially to tumor development and play a major role in the unlimited growth of

cancer cells (Porth, et al., 2002).

1.8. Chemotherapy

The term cytotoxic and antitumor drug applies to any drug that shows toxic effect on

cells and inhibits the proliferation of cancerous cells. These drugs generally useful in

cancer chemotherapy to control the malignancies or cancerous growths in the body.

The essential approach in the treatment of cancer is the removal or destruction of cancer.

Several different techniques are commonly employed, including surgery, radiation,

immunotherapy and chemotherapy, which each technique shows the different advantages

and disadvantages towards cancer. All treatments using medicines can be termed

―chemotherapy‖, the word is most often employed to describe treatment by strong

cytotoxic drugs for serious diseases such as cancer. The principal mode of action of

cytotoxic drugs is the damage against DNA or induces faulty division. It means that

chemotherapeutic drugs interfere the division of cancer cells and cause the cancer cell

damage. The essential difficulty in chemotherapeutic drugs is not able to selectively

damage only cancer cells. The majority of chemotherapeutic drugs can be divided into

(Table. 2)

Table 2: Examples of anticancer drugs

Category Examples

Alkylating agents Cisplatin, Carboplatin and Oxaliplatin

Anti-metabolites Azathioprine and Mercaptopurine

Vinca alkaloids Vincristine, Vinblastine and Vinorelbine

Podophyllotoxin Etoposide and Teniposide

Taxanes Paclitaxel and Docetaxel

Topoisomerase inhibitors Irinotecan and Topotecan

Cytotoxic antibiotics Dactinomycin and Doxorubicin

Tyrosine kinase inhibitors Imatinib, Gefitinib

Monoclonal antibodies Trastuzumab, Rituximab

Hormone agonists Progestogens

Normal tissues with rapidly growing cells are also damaged to varying degrees, causing

often severe side effects. The type of chemotherapeutic drug administration depends on a

number of these factors: 1) the type of cancer, 2) where the cancer started, 3) whether the

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cancer has spread to other parts of the body and 4) the general health of the person.

Chemotherapy is often used as an additional safeguard after surgery or in conjunction

with radiotherapy, to destroy any remaining cancer cells and reduce the chance of the

cancer returning. In addition, chemotherapy may be given to try to control the disease, or

to reduce symptoms and improve quality of life (Devidson, 2006).

1.9. Mechanism of action of anticancer drugs

Currently it is known that anticancer agents can arrest cell division by one or more

mechanism, the most important being:

• Microtubule interface

• Topoisomerase poisoning or topoisomerase catalytic inhibition

• DNA Alkylation

• DNA inhibition

• Protein synthesis inhibition

• Immune mechanism

• Lipooxygenase inhibition

• Microtubule interfering substance

1.10. Cancer chemoprevention

Although some progresses have been made in cancer diagnosis and treatments, the high

incidence and low survival rate of patient have still been reported. The development of

new therapeutic approach remains one of the most challenging in cancer research.

Chemoprevention of cancer has become a promising approach due to chemotherapy,

surgery and radiation have not been fully effective (Moongkarndi and Kosem, 2006). The

term chemoprevention, also called ―chemoprophylaxis‖, is coined to parallel the term

chemotherapy. Chemoprevention means the prevention of cancer development and

chemotherapy means the cancer treatment by killing or inducing cancer cell death.

Cancer chemoprevention is defined by Sporn in 1976 as the use of natural, synthetic or

biologic chemical agents to reverse, suppress, delay or prevent either the initiation phase

of carcinogenesis or the progression of neoplastic cells to metastasis (Sporn and Suh,

2000). Multistep carcinogenesis describes a stepwise accumulation of alterations, both

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genotypic and phenotypic. Arresting one or several steps may impede or delay the

development of cancer. Therefore, chemopreventive agents show promise for preventing

and reversing cancer development, or delaying the recurrence of cancer. An approach to

reducing cancer risk that either prevents or stops carcinogenesis in its early stages is a

logical and perhaps the best strategy to reduce the overall cancer burden. The adage an

ounce of prevention is worth a pound of cure‖ still holds true (Sporn, 1996). The concept

of using chemopreventive agents to reduce cancer risk, either prevent DNA damage or

suppress the appearance of cancer phenotypes, is firmly based on epidemiologic,

laboratory and clinical researches from the last two decades. It was indicated that specific

compounds may influence carcinogenesis at various sites, including the oral cavity,

esophagus, stomach, colorectum, lung, breast and prostate (Wattenberg et al., 1992).

Epidemiologic studies have provided the initial leads for identification of numerous

candidate chemopreventive agents. Promising chemopreventive agents are investigated

including micronutrients (such as vitamin A, C and E, beta-carotene, calcium and

selenium), naturally occurring phytochemicals (such as indoles, polyphenols,

isothiocyanates, flavonoids, monoterpenes, organo sulfides) and synthetic compounds

(Block, et al., 1992). (Such as vitamin A derivatives, piroxicam, tamoxile and oltipraz).

Broadly defined on the basis of their mechanisms of action, chemopreventive agents can

be grouped into two general classes:

a) Blocking agents prevent carcinogenic compounds from reaching or reacting with

critical target sites by preventing the metabolic activation of carcinogens or tumor

promoters by enhancing detoxification systems or by trapping reactive carcinogens

(Kelloff, et al., 1994).

b) Suppressing agents prevent the evolution of neoplastic process in cells that would

otherwise become malignant. Mechanisms of action for suppressing agents are not

well understood (Wattenberg, 1996). Certain chemopreventive agents may exhibit

several different mechanisms of action simultaneously.

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1.11. Medicinal plants for cancer chemotherapy and chemoprevention

Newman and Cragg (2007) showed that, over whole category of anticancer drugs

effectively available to the West and Japan, the 175 available anticancer drugs were

approved during 1940s-2006.

Figure 3: Flow chart of sequence for the study of plants used in traditional medicine.

For thousands of years, human has used natural substances, especially plants, to relieve

pain, heal wound and maintain health. The term of phytotherapy was coined by the

French physician Henri Leclerc (1870-1955). Phytotherapy is the treatment and

prevention of disease using plants, plant parts and preparations made from them (Weiss

and Fintelmann, 2000). The plants traditionally used in phytotherapy are called medicinal

plants or herbs. An estimated 3 billion people worldwide continue to use traditional plant

medicines as their primary form of healthcare. Many medicines were discovered by a

targeted knowledge based ethnobotanical approach (Walsh, 2002). Researchers recorded

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plant-based medicinal cures and then analyzed active ingredients in this plant. Plants

produce a wide array of bioactive molecules via secondary metabolic pathways. Most of

these probably evolved as chemical defense agents against infections or predators. The

bulk of plant-derived medicines can be categorized into a number of chemical families,

including alkaloids, flavonoids, terpenes, terpenoids, steroids, coumarins, quinines,

salicylates and xanthenes (Walsh, 2002).

Current research in drug discovery from medicinal plants involves a multifaceted

approach combining botanical, phytochemical, biological and molecular techniques

(Figure 6). Medicinal plant drug discovery continues to provide new and important leads

against various pharmacological targets including HIV/AIDS, Alzheimer‗s, malaria, pain

and cancer. Although drug discovery from medicinal plants continues to provide an

important source of new drug leads, numerous challenges are encountered including the

procurement of plant materials, the selection and implementation of appropriate high-

throughput screening bioassays, and the scale-up of active compounds (Balunas and

Kinghorn, 2005). Despite intensive investigation of terrestrial flora, it is extimated that

only 5% to 15% of the approximately 2, 50, 000 species of higher plants have been

systematically investigated, chemically and pharmacologically (Budman, et al., 2003).

Cancer is a common enemy of mankind. Substantial advances have been made in the

treatment, but the conquest of cancer remains and imposing challenge. Plants have

proved to be a very important source of pharmacologic substances due to epidemiological

studies have suggested that a reduced risk of cancer is associated with high consumption

of vegetables and fruits. Thus, the cancer chemotherapeutic and chemopreventive

potentials of naturally occurring phytochemicals are of great interest (Han, 1994). The

preclinical development of chemotherapeutic and chemopreventive agents includes an

assessment of their efficacy using in vitro and cell based mechanistic assays and in vivo

screens in animal models against carcinogenesis that are representative of human cancers.

The most promising agents are characterized more fully in the animal models to evaluate,

for example, dose-response curves and dosing regimens (Park and Pezzuto, 2000).

Compounds that showed high efficacy and low toxicity in animal studies are considered

for testing in humans. Potential chemotherapeutic and chemopreventive agents selected

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for testing in people at high risk of developing cancer must have low toxicity compared

with the drugs used to treat existing cancer.

Table 3: List of anticancer plants

Name of the plant Family Parts used

Azadirachta indica Meliaceae Bark

Asparagus racemosus Liliaceae Root

Aphanamixis polystachya Meliaceae Bark

Aloe barbadensis Liliaceae Leaf juice

Alium cepa Liliaceae Bulb

Buteamono sperma Fabaceae Bark

Bauhinia variegate Caesalpinaceae Root

Bacopa monnieri Scropulariaceae Whole plant

Cassia absus Caesalpinaceae Leaves

Cassia auriculata Caesalpinaceae Root

Cassia senna Caesalpinaceae Leaves

Catunaregum spinosa Rubiaceae Bark/Fruit

Daucus carota Apiaceae Root

Embelia ribes Myrsinaceae Fruit

Flacourtia jangomos Flacourtiaceae Bark/Leaf

Jatropha curcas Euphorbiaceae Leaves,seed,oils

Kaempferia galangal Zingiberaceae Rhizome

Limonia acidissima Rutaceae Fruit

Macrotyloma uniflorum Fabaceae Seed

Nicotiana tabacum Solanaceae Leaves

Operculina turpethum Convolvulaceae Root

Rhinacanthus nasuta Acanthaceae Whole plant

Symplocus cochinchinensis Symplocaceae Bark

Xanthium strumarium Compositae Root

Zanthoxylumarmatum Rutaceae Bark,Fruit

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Many plants are used to treat cancer in ethno medical practices in different parts of the

world. According to Hartwell (Hartwell, 1971) it has been estimated that more than 3000

species of plants have been used throughout the world to treat cancer. In addition to the

flowering plants, mushrooms (Mascarenhas, 1994) and ferns (Rastogi and Dhawan,

1982) have been advocated for the treatment of cancer. Cancer is a disease which still

eludes effective treatment and satisfactory cure. There are over 150 recognized types of

cancers in man and they account for 90% of the death throughout the world. The

incidence of cancer is on the increase in India and it is one of the 10 leading causes of

death today in India.

There are some important plant derived anti-cancer drugs which have passed clinical

trials with reasonable efficacy and some levels of safety. They are vinblastin, vincristine

(Cathranthus Roseus), toxoids (Taxus brevifolia and Taxus baccata) and

Phodophyllotoxin and its derivative etoposide (Phodophyllum sp).

Some of the anticancer plants subjected to some level of Ethanopharmacological studies

based of Ethnomedical leads in India have been reported by several researchers.

There is long list of plants (Table 3) claimed to have varying levels of anticancer

properties (Dhanamani, et al., 2011) About 25- 30 % of the anti tumor drugs in

development are of plant origin. Presently, the role of anti-oxidants is well established in

the prevention or cure of many diseases.

1.12. Anticancer drugs derived from plants

Plants have a long history of use in the treatment of cancer. It is significant that over 60%

of currently used anticancer agents are derived in one way or another from natural

sources . The National Cancer Institute (NCI) collected about 35,000 plant samples from

20 countries and has screened around 114,000 extracts for anticancer activity (Shoeb,

2006). Of the 92 anticancer drugs commercially available prior to 1983 in the US and

among worldwide approved anticancer drugs between 1983 and 1994, 60% are of natural

origin (Cragg et al., 1997). In this instance, natural origin is defined as natural products,

derivatives of natural products or synthetic pharmaceuticals based on natural product

models.The search for anti-cancer agents from plant sources started in earnest in the

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1950s with the discovery and development of the vinca alkaloids, vinblastine and

vincristine, and the isolation of the cytotoxic podophyllotoxins. These discoveries

inspired the United States National cancer institute (NCI) to initiate an extensive plant

collection and isolation of novel anticancer lead molecules from plants. The first

anticancer agents advanced into clinical use were the so-called vinca alkaloids,

vinblastine and vincristine, isolated from the Madagascar periwinkle, Catharanthus

roseus G. Don. (Apocynaceae). More recent semisynthetic analogs of these agents are

vinorelbine (VRLB) and vindesine (VDS). These agents are primarily used in

combination with other cancer chemotherapeutic drugs for the treatment of a variety of

cancers, including leukemias, lymphomas, advanced testicular cancer, breast and lung

cancers, and Kaposi‘s sarcoma (Cragg and Newman, 2005).

Podophyllotoxin, is a non-alkaloid toxin lignan extracted from the roots and rhizomes of

Podophyllum peltatum Linnaeus (commonly known as the American mandrake or

Mayapple), and Podophyllum emodii Wallich from the Indian subcontinent, have a long

history of medicinal use, including the treatment of skin cancers and warts (Stahelin

1973). The Etoposide and Teniposide, which are semi-synthetic derivatives of the natural

product, epipodophyllotoxin (an isomer of podophyllotoxin) were proved active against

various cancers, used clinically in the treatment of lymphomas and bronchial and

testicular cancers (Shoeb et al., 2006).

A more recent discovered anticancer drug from plant origin are Taxanes. Paclitaxel

(taxol) initially was isolated from the bark of Taxus brevifolia Nutt and taxus baccata L.

A semisynthetic derivative of Paclitaxel docetaxel were become important class of

anticancer drugs, now clinically useful in the treatment of breast, ovarian, and non-small

cell lung cancer(Kingston, 2007; Hait et al., 2007).

Another important addition to the anti-cancer drug armamentarium is the class of

clinically active agents derived from Camptothecin, which is isolated from the Chinese

ornamental tree, Camptotheca acuminata Decne (Nyssaceae) (Rahier et al., 2005). The

semisynthetic derivatives of Campothecin, Topotecan and Irinotecan were also clinically

developed as anticancer drugs. Topotecan is used for the treatment of ovarian and small