ANTICANCEROUS MEDICINAL PLANTS: A REVIEW Jamal Akhtar Ansari1,2, Homa Jilani Khan1,2, Nishat Fatima1,2, Vijai Lakshmi1, Mohammad Kaleem Ahmad1, Abdul Rahman Khan1, Abbas Ali Mahdi1* Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India, 226 003 1 2 Department of Chemistry, Integral University, Lucknow, Uttar Pradesh, India, 226 026 *corresponding author: Professor Abbas Ali Mahdi Department of Biochemistry, King George’s Medical University Lucknow-226 003 Uttar Pradesh, India Telephone: (+91-522) 2253030, 2257888 Fax: (+91-522) 2257539 Mobile: +91-9415007706 Email: mahdiaa@rediffmail.com ABSTRACT Natural medicinal plants have played a potent role in drug discovery and treatment of various human ailments since prehistoric time. Many of precious anticancer lead molecules; vinca alkaloid, vinblastine, vincristine, camptothecin, taxanes have been isolated and characterized from these plants and are in clinical use all over the world. Strategic options based on natural product drug discovery, ethnopharmacology and traditional medicines are re-emerging to offer good base as an attractive discovery engine. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicines. Based on recent published data this article reveals a detailed review of ethno medicinally important anticancerous plants. It will be helpful to explore the therapeutic value of plants and isolation of phytochemicals from them may be used in developing anticancer drugs. Keywords: Natural plants, drug discovery, anticancerous plants, phytochemicals. INTRODUCTION Natural plants have been used for remedial purposes in the treatment of human ailments since prehistoric times and have been an exemplary source of medicines. Unani, Ayurveda, Siddha and Indian literatures mention the use of plants in treatment of various human ailments. India has about 45000 plant species and among them, several thousands have been claimed to possess medicinal properties. Recent data suggests that 80% drug molecules are natural products or natural compounds inspired (Harvey, 2008). Studies on sources of new drugs from 1981 to 2007 reveal that almost half of the drugs approved since 1994 are based on natural products (Butler, 2008). About 60% of anticancer and 75% of anti-infective drugs approved from 1981-2002 could be traced to natural origins (Gupta et al., 2005). It is precisely the chemistry of natural products, which has fostered many of the new developments in these areas, because of the variety of compound types available. It would be cheaper and perhaps more productive to reexamine plant remedies described in ancient literatures (Holland, 1994). However, research on natural medicinal plants has lately undergone explosive growth owing to advances in drug discovery, isolation techniques, synthetic methods, physiochemical measurements and new concepts. Natural phytochemicals derived from medicinal plants have gained significant recognition in the potential management of several human clinical conditions, including cancer (Mehta et al., 2010; Desai et al., 2008; Guilford and Pezzuto, 2008). Many active chemical compounds obtained from traditional medicine sources could serve as good scaffolds for rational drug design. Most of these compounds are part of routinely used traditional medicines and hence their tolerance and safety are relatively better known than any other chemical entities that are new for human use (Patwardhan et al., 2004). Thus, traditional medicine based bioprospecting offer unmatched structural variety as promising new leads (Koehn and Carter, 2005). Large number of promising molecules have come out of Unani and Ayurvedic experimental base including Rauwolfia alkaloids for hypertension, Psoralens in Vitiligo, Holarrhena alkaloids in Ameobiasis, Guggulsterons as hypolipidemic agents, Mucuna pruriens for Parkinson’s disease, Piperdine as bioavailability enhancers, Baccosides in mental retention, Picrosides in hepatic protection, Phyllanthins as antiviral, Curcumines in inflammation, Withanolide, and many other steroidal lactones and glycosides as immunomodulators (Patwardhan, 2000). Moreover, atropine isolated from Atropa belladonna used as anticholinergic, Pennicillium sp. gives pennicillium a good antibiotic, Digitalin, Digoxin, and Digitoxin are antiarrythmic from Digitalis purpurea and Cinchona ledgeriana produces antimalarial Quinidine. These drugs have been cornerstone of treatment for many diseases in medical science. Moreover, much research has been geared towards the evaluation of plant extracts as prophylactic agents, which offer great potential to inhibit the carcinogenic process. Simultaneously, the synergistic effects of the cocktail of plant metabolites and the multiple points of intervention offer higher efficacy during chemoprevention regimens (Guilford and Pezzuto, 2008). The preventive mechanisms of tumor promotion by natural phytochemicals range from the inhibition of genotoxic effects, increased antioxidants and anti-inflammatory activity, inhibition of proteases and cell proliferation, protection of intracellular communications to modulate apoptosis and signal transduction pathways (Soobrattee et al., 2006). A number of anti-cancer agents have been isolated from various plant sources like Catharanthus roseus, Podophyllum species, Taxus brevifolia, Campotheteca acuminate, Curcuma longa. Structurally anticancerous compounds obtained from above sources have been classified into four major types viz., Vinca alkaloids, Epipodophyllotoxin lignans, Taxane diterpenoids and Campothecin quinoline alkaloid derivatives. Vinca alkaloids belong to an important class of anticancer drugs. Campothecin and its other derivative Exatecan, isolated from Campothecin acuminate, have potent anticancer activity. Taxanes obtained from the plant Taxus brevifolia, Taxus bacata. Curcumin longa, is Indian spices which produces Curcumin, a poly phenolic compound now finding its application as potential anti-cancer compound. These new chemopreventive agents are being identified based on their ability to modulate one or more specific molecular events. The discovery of effective herbs and elucidation of their underlying mechanisms could lead to the development of an alternative and complementary method for cancer prevention and/or treatment. The Indian sub-continent has great botanical diversity and widespread use of traditional medicine practice known as Ayurvedic medicine; however, only a relatively small number of these plants have been subjected to scientific evaluation for their potential anticancer effects (Krishnaswamy, 2008). The World Health Organization’s Commission on Intellectual Property and Innovation in Public Health has also duly recognized the potential role of traditional medicines in drug development for affordable health solutions (Patwardhan, 2005). Therefore natural product based drug discovery, ethnopharmacology, traditional, complementary and alternative medicines are re-emerging as new strategic options (Patwardhan and Mashelkar, 2009). Based on an analysis of recent published data this review introduces to some of the natural medicinal plants which have been reported as anticancerous plants. Artemisia vulgaris Family: Compositae Common name: Mugwort Globally A. vulagaris occurs in climatic region and is reported to occur from the high mountainous regions of the Northern Himalayas to warm temperature regions of South America. It is used as an antibacterial, anthelmintic, anti-inflammatory, antiseptic, antispasmodic, carminative, digestive, diuretic and nervine and it also has purgative properties. Study reports anticancer activity of Artemisia vulgaris inflorescence aqueous extract against human prostate cancer PC-3 cells, human breast carcinoma T47D cells and colon cancer RKO cells for 24, 48 and 72h treatment. Study show that Artemisia vulgaris exhibited 8-65% inhibition PC-3 cells, 5-42% T47D cells, 7-53% RKO cells at concentration of 1.0 to 10% for 24 hours. An increased cell growth inhibition was observed at 24 to 72 hours incubation of these cells (Akbar et al., 2011). Artemisia species also showed good cytotoxicity against three human cancer cell lines, MCF7, A549 and HeLa (Sura et al., 2011). Another study conducted by Emami et al. for the toxicity investigation of Artemisia sp. against human Caucasian hepatocyte carcinoma (HepG-2) and human Caucasian larynx carcinoma (Hep-2) cell lines and cytotoxic effects against two human tumor cell lines Hep2 and HepG2 were determined by quantitative MTT assay. Results showed concentration- and time-dependent toxicity (Seyed et al., 2009). Artocarpus obtusus Family: Moraceae Common name: Breadfruit The Artocarpus species belong to Moraceae family which has about 55 species and is widely distributed throughout India, Sri Lanka, Burma, Thailand, China, Taiwan and Malaysia. It is traditionally used for the treatment of diarrhea, fever, liver cirrhosis, hypertension, diabetes, inflammation, malaria, ulcers, wound, and for tapeworm infection (Khan et al., 2003; Su et al., 2002; Patil et al., 2002; Boonlasksiri et al., 1992; Jong et al., 1992). Hashim et al. have isolated three new xanthones, pyranocycloartobiloxanthone A, pyranocycloartobiloxanthone B, and dihydroartoindonesianin C. Anticancer activity has been analyzed against human promyleocyctic leukemia (HL60), human chronimyeloid leukemia (K562) and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A showed good cytotoxicity against these three cell lines and it also had antiproliferative activity and apoptotic promoter activity towards HL60 and MCF7 cell lines (Hashim et al., 2012). Azadirachta indica Family: Meliaceae Common name: Indian Neem Azadirachta indica commonly known as Neem is widely distributed in Asia, Africa and other tropical parts of the world. A. indica is known to have attained prominence medicinal properties as reported in Ayurveda, Unani and Homeopathic system of medicine and it is also used worldwide for the treatment of various diseases. It has been reported to be anti-inflammatory, anti-pyretic, hypoglycaemic and also exhibits antimicrobial and anticancerous properties (Parida et al., 2002). Numerous studies showed hepato-protective effects of A. indica 5% w/v aqueous extract on Diethyl Nitrosamine (DEN) and 2Acetylaminofluorene (AAF) induced-hepatocacinogenesis in Spraque-Dawley rats (Manal et al., 2009). Mahapatra et al. investigated the novel targets of the anticancer activity of ethanol extract of neem leaves in vitro and evaluated its in vivo efficacy in the prostate cancer models. Many studies demonstrate that neem leaves ethanolic extract-containing natural bioactive compounds 2,3-dehydrosalannol, 6-desacetyl nimbinene, and nimolinone inhibited in vitro cell proliferation and in vivo tumor growth (Saswati et al., 2011). Ethanolic neem leaf extract has also been investigated for the apoptosis inducing capacity during 7, 12-demethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis using the apoptosis-associated proteins Bcl-2, Bim, caspase 8 and caspase 3 as markers. Administration of ENLE inhibited DMBA-induced hamster buccal pouch (HBP) carcinogenesis with induction of Bim and caspases 8 and 3 and inhibition of Bcl-2 expression. Study suggested that the chemopreventive effects of extract may be mediated by induction of apoptosis (Subapriya et al., 2005). Othman et al. had investigated the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice. In situ RT-PCR showed that c-Myc oncogene expression was down regulated under stimuli of 500 mg/kg of ethanolic neem leaf extract (Fauziah et al., 2012). Bacopa monnieiri Family: Scrophularaiceae Common name: Brahmi The whole plant constitutes the well known drug brahmi. It is used as astringent, laxative, carminative, digestive, depurative, cardiotonic, bronchodilatory and antiulcer agent. There are reports that brahmi also has good anticancer property. Prakash et al. evaluated the anticancer activity of Bacoside A (containing Bacoside A3) isolated from whole plant of Bacopa monnieiri In Vitro against Human Breast Cancer (MCF-7), Human colon adeno carcinoma (HT-29) and Human Kidney carcinoma (A-498) cell lines and In Vivo against Ehrlich ascites carcinoma (EAC) tumor bearing mice. Study concluded that Bacosides rich fraction BM-2B (31.38 % Bacoside A containing 8.09% Bacoside A3) from Bacopa monnieiri whole plant exhibited potent anticancer activity as demonstrated by In Vitro cytotoxicity using MCF-7, HT-29 and A-498 cell lines as well as EAC induced tumour in mice (Prakash et al., 2011). Beorhaavia diffusa Family: Nyctaginaceae Common name: Punarnava, Snathikari B. diffusa is a perennial herb from a fusiform root and belongs to the family Nyctaginaceae. According to Ayurveda and Unani Punarnava it is bitter, cooling, and astringent to bowels, useful in biliousness, blood impurities, leucorrhoea, anemia, inflammations, heart diseases and asthma. The leaves are useful in dyspepsia, tumours, spleen enlargement, and abdominal pains. Seeds are tonic expectorant, carminative, useful in lumbago and scabies. Studies demonstrate that 80% hydro-alcoholic extract of B.diffusa leaves showed cancer chemopreventive property of DMBA- induced cancer carcinogenesis in mice by preventing the promotional events in the mouse skin through free radical scavenging mechanism (Bharli et al., 2003). Two rotenoids isolated from B. diffusa, boeravinones G and H, have been found to potentially inhibit the drug efflux activity of breast cancer resistance protein (BCRP/ABCG2), a multidrug transporter responsible for the cancer cell resistance to chemotherapy (Ahmed et al., 2007). Blumea balsamifera Family: Asteraceae Common name: Ngai camphor B. balsamifera is a half woody, strongly aromatic shrub, densely and softly hairy, 1 to 4 meters high and found in China, Hainan, Bhutan, Cambodia, Laos, Indonesia, Malaysia, Thailand, and Vietnam. Methanolic extract of B. balsamifera induced cell cycle arrest at G1 phase via decrease in expression of cyclin-E and phosphorylation of retinoblastoma (Rb) protein in both dose and time-dependent manner. It also reduces the level of a proliferation related ligand which stimulates tumor cell growth. B. balsamifera extract is also effective against human hepatocellular carcinoma cells. Blumea balsamifera DC, led to isolation of nine flavonoids. The isolated compounds consisted of two dihydroflavonols, dihydroquercetin-4-methyl ether (1) and dihydroquercetin-7,4´-dimethyl ether (2), two flavanones, 5,7,3´,5´-tetrahydroxyflavanone (3) and blumeatin (4), three flavonols, quercetin (5), rhamnetin (6) and tamarixetin (7), two flavones, luteolin (8) and luteolin-7-methyl ether (9). Compounds (1-5 and 9) were evaluated for cytotoxicity against oral cavity cancer (KB), Breast cancer (MCF-7) and Small cell lung cancer (NCI-H187) cell lines. Compounds 2, 4, and 9 were active against the KB cells with the IC50 values of 17.09, 47.72 and 17.83 ug/ml, respectively. Compounds 2, 3 and 5 exhibited moderate activity against the NCI-H187 cells. Luteolin-7-methyl ether (9) showed strong cytotoxicity against human lung cancer (NCI-H187) cell lines and moderate toxicity against oral cavity cancer (KB) cell lines (Saewan et al., 2011). 2.7. Bryonia laciniosa Family: Cucurbitaceae Common name: Bryony, Snakeweed, Shivlingi It is native to Europe, Mediterranean region and Central Asia (Kirtikar and Basu, 1987). As a folk medicine, the plant is used in treatment of gastrointestinal, respiratory, rheumatic and metabolic disorders, as well as in liver and infectious diseases (Gabrielian and Gevorgovich, 1997; Acharya, 2007). Moghe et al. have tested in vitro cytotoxicity of B. laciniosa leaves water, methanol, and chloroform extract on human Breast adenocarcinoma (Mcf-7), Human squamous cell carcinoma; cervix (SiHa) cell lines and one non cancer normal cell line Vero (monkey kidney cell line). The results showed that aqueous extract posses cytotoxicity to cancer cells and are able to kill all cancer cells without leaving residual population (Alpana et al., 2011). Calotropis procera Family: Ascelpiadaceae Common name: Apple of Sodom, Aak Calotropis procera is a shrub or small tree up to 2.5 m. All part of plant exudes white latex when cut or broken. It is used for the treatment leprosy, ulcers, piles and tumors (Kumar and Arya, 2006). The root extract of C. Procera has been found to produce a strong cytotoxic effect on COLO 320 tumor cells. Recently, a hemi synthetic derivative of a cardenolide isolated from the root barks of C. Procera showed a strong cytotoxic effect on several human cancer lines, a high in vivo tolerance to tumor growth and prolonged survival in the human xenograft models of nude mice (Van et al., 2005). Chemopreventive effect of C. Procera latex (DL) was studied in the X15 myc- transgenic mice. Treatment of mice with DL (400 mg/kg) for a period of 15 wk protected these mice from malignant changes occurring in the liver. The methanolic extract (ME) and its fractions (non-polar and polar) of DL were evaluated for cytotoxicity using MTT assay on two different cell lines, viz., (Huh-7) and COS-1 cells. Further evaluation of cytotoxic effects of DL on hepatoma (Huh-7), non-hepatoma (COS-1) and non-cancerous (AML12) cell lines showed that the cytotoxic activity was associated with one of the polar fractions of DL (Choeden et al., 2006). The cytotoxic potential of stem organic extracts from Calotropis procera was evaluated against tumor cell lines HL-60, CEM (human leukemia), HCT-8 (human colon cancer) and B-16/F10 (murine melanoma) by MTT assay. Subsequently, samples considered cytotoxic were tested for antimitotic activity on sea urchin egg development and in vivo antiproliferative activity in mice bearing Sarcoma 180 tumor. Among five extracts (hexane, dichloromethane, ethyl acetate, acetone and methanol) study showed that ethyl acetate, acetone and methanol stem extracts from C. procera possess promising in vitro antiproliferative activity on cancer lines and sea urchin eggs. Moreover, ethyl acetate and acetone extracts were able to reduce in vivo tumor growth of Sarcoma 180 transplanted mice in the presence of liver and kidneys reversible toxic effects (Hemerson et al., 2010). Antitumor potential of root extracts of Calotropis procera in Methanolic extract (CM), hexane extract (CH), aqueous extract (CW) and ethyl acetate (CE) and its possible mechanism against Hep2 cancer cell lines has also been investigated. CM, CH and CE possessed cytotoxicity, whereas CW did not. Study showed inhibition of proliferation of Hep2 cells via apoptotic and cell cycle disruption based mechanism (Rajani et al., 2009). Cassia occidentalis Family: Leguminoseae Common name: Kasonda, coffee senna It is commonly found throughout India. In Indian system of medicine the plant has been documented as thermogenic, puragative, expectorant, diuretic, and is used in the treatment of leprosy, erysipelas, ulcers, cough, bronchitis, constipation, flatulence, dyspepsia, menstrual problems, tuberculosis, and anemia. It was observed that aqueous extract of C. occidentalis (whole plant) had more potential than hydroalcoholic and alcoholic extracts against Colon (HCT-15, SW-620), Prostate (PC-3), Breast (MCF-7), Cervix (SiHa), and Ovary (OVCAR-5) human cancer cell lines at 100, 30, and 10 μg/ml in a dosedependent manner. Hydro-alcoholic extract showed highest cytotoxicity against HEP-2, followed by Colon (COLO 205) cancer cell line. Alcoholic extract showed comparatively less activity against these cell lines (Madhulika and Ajit, 2010). Catharanthus roseus Family: Apocynaceae Common name: Madagascar periwinkle It is a perennial plant commonly seen in tropical countries. The plant produces beautiful flowers with a variety of colours such as purple, pink and white. Historically, Madagascar periwinkle had been used for treatments of various ailments e.g. diabetes mellitus, high blood pressure and infections (Taylor et al., 1975). Two of very important anticancer drugs Vincristine and Vinblastine have been isolated and characterized. Vincristine is used in the chemotherapeutic regimen for Hodgkin’s lymphoma, while Vinblastine is used for childhood leukemia (Johnson et al., 1963). Various studies suggest that the presence of other antineoplastic alkaloids in the plant (El-Sayed et al., 1983). Crude extracts of C. roseus using 50 and100% methanol had significant anticancer activity against different cell types in vitro (Ueda et al., 2002). Siddique et al. have isolated two compounds catharanthine and vindoline and have studied five extracts with two pure compounds for cytotoxicity activity. The preliminary cytotoxicity study demonstrated dose independent cytotoxic activity of the methanol extract of C. Roseus when screened against HCT-116 colorectal carcinoma cell line. n-hexane, chloroform and methanol fractions also showed dose independent cytotoxicity with chloroform fraction showing the highest activity. Water fraction showed only a minor cytotoxic activity. Cathranthine showed the most promising activity (Siddiqui et al., 2010). Cichorium intybus Family: Compositae or Asteraceae Common name: Chicory, Kasni The whole plant contains a number of medicinal properties. It is cultivated throughout India. It is used as a liver tonic, cardiotonic, diuretic, cholagogue, depurative, emmenagogue, in hepatomegaly, inflammations, jaundice, splenomegaly, amenorrhea and dyspepsia (Schaffer et al., 2005; Tousch et al., 2008). Studies showed that seeds of C. Intybus against PC-3 cell exhibit growth inhibition of 2-30% at concentration of 1.0 to 10% for 24 hours, moreover, there was 6-26% growth inhibition of RKO cells as well as T47D cells growth inhibition of 2-21%. Moreover, studies demonstrated that cell growth inhibition increased was observed at similar concentration after 24 to 72 hours of incubation (Akbar et al., 2011). Citrus maxima Family: Rutaceae Common name: Pomelo Pomelo is the indigenous plant of tropical part of Asia. The pulp is antitoxic, appetizer, cardiac stimulant and stomach tonic (Ontengo et al., 1995). Experiments performed by KunduSen et al. found that intraperitonial administration of methanolic extract of C. Maxima at the dose level of 200 and 400 mg/kg bw increased the life span of nonviable tumor cell count and decreased the tumor volume (KunduSen et al., 2011). Immature hexane fruit extract of pomela has also shown its antiproliferative activity against U937 human luekemia cell line (Lim et al., 2009). Dysoxylum binectiferum Family: Meliaceae Common name: Lasunni amari The plant D. binetiferum is generally occurring wild in the foorthills of the Himalyas and Western Ghats, South East Asian countires. Traditionally many plants from genus Dysoxylum have been used for medicinal purposes in the treatment of facial distortion in children, lump under the skin and other skin irritations. Rohutikine an alkaloid isolated from D. Binectiferum has potent insectidal and pesticidal activity (Lakshmi et al., 2012). Rohitukine is a chromane alkaloid possessing anti-inflammatory, anticancer and immuno-modulatory properties. Flavopiridol, a semi-synthetic derivative of rohitukine is a potent CDK inhibitor and is currently in Phase III clinical trials. Fusarium proliferatum (MTCC 9690) an endophytic fungus isolated from the inner bark tissue of Dysoxylum binectariferum Hook.f (Meliaceae).The endophytic fungus produces rohitukine when cultured in shake flasks containing potato dextrose broth. Methanolic extract of the fungus was cytotoxic against HCT-116 and MCF-7 human cancer cell lines (Mohana et al., 2012). Emblica officinalis Family: Euphorbiaceae Common name: Amla The species is native to India and also grows in tropical and subtropical regions including Pakistan, Uzbekistan, Srilanka, South East Asia, China and Malaysia. The fruits of E.offinalis are widely used in the Aryuveda and are believed to increase defense against diseases. It has its beneficial role in cancer, diabetes, liver treatment, heart trouble, ulcer, anaemia and various other diseases. Similarly, it has applications as antioxidant, immunomodulatory, antipyretic, analgesic, cytoprotective, antitussive and gastroprotective agent. It enhances natural killer (NK) cells in various tumors and reduced the ascites and solid tumor induced by Dalton’s lymphoma ascites cells in mice. Cyclophosphamide is one of the most popular alkylating anticancer drugs inspite of its toxic effects. Aqueous extract of E. officinalis reduced immunotoxicity, hematotoxicity and mutagenecity, in mice treated with cyclophosphamide (Haque et al., 2001). Study demonstrates the in vitro cytotoxicity of ethanolic extract of whole plant against five human cancer cell lines namely of lung (A-549), liver (Hep-2) colon (502713 HT-29) and neuroblastima (IMR32). The activity was done using 100μg/ml of the extract. Against lung (A-549) cell line the plant extract showed 82% growth inhibition. In case of liver (Hep-2) it showed no activity reported, where as in case of colon 502713 cell line plant extract showed maximum activity. In case of HT-29 liver human cancer line and IMR-32 neuroblastima cell line plant extract showed 98% and 97% activity, respectively (Satish et al., 2012). Moreover, aqueous extract of E. officinalis was found to be cytotoxic to L 929 cells in culture in dose dependent manner (Jose et al., 2001). Moringa oleifera Family: Moringaceae Common name: Horseradish, Sahijan It occurs in native to the sub-Himalayan tracts of India, Pakistan, Bangladesh and Afganistan. This rapidly growing tree has been used traditionally for many remedial purposes. The root of young trees and also the root bark are considered rubefacient, vescicant carminative, stomachic, and abortifacient; among other uses, they are commonly applied externally to cure inflammatory swellings. The flowers and roots contain pterogospermin, an antibiotic that is highly effective in the treatment of cholera (Lizzy et al., 1968). Studies have found that Moringa compounds, benzyl isothiocyante (BITC) and phenyl isothiocyante (PEITC) induced apoptosis in ovarian cancer cells in vitro. Beta-sitosterol, glycerol-1-(9octadecanoate), 3-O-(6’-O-oleolyl-beta-D-glucosepyranosyl)-beta-sitosterol and beta-sitosterol-3-O-betaD-glucopyranoside of Moringo oleifera have been identified as anticancer agents. Nair et al found that aqueous extract of Moringo tree is cytotoxic against HeLa cell lines (Nair and Varalakshmi, 2011). Study demonstrates the anticancer activity of leaves and fruits of M. oleifera in in vivo exploration on B16 F10 melanoma tumor. The mice were treated with hydromethanolic (HMF1, HML1) and methanolic extracts (MF2, ML2) at a dose of 500mg/kg b.wt. and further ML2 at 1g/kg b.wt. Study revealed that leaves and fruits were effective in tumor growth while leaves were most effective in increasing the survival time (Purwal, 2010). Seeds of Moringa oleifera Lam afforded 4-(4´ Oacetyl- a-L-rhamnosyloxy)benzyl isothiocyanate (1), 4-(a-L-rhamnosyloxy)benzyl isothiocyanate (2), squalene (3) and sitosterol (4). Isothiocyanate 1 and 2 were evaluated for cytotoxicity against non-small cell lung adenocarcinoma (A549) and colon carcinoma (HCT 116) and were cytotoxic to these cell lines (Consolaction et al., 2012). Nigella sativa Family: Ranunculaceae Common name: Kalaunji, Black cumin N. sativa commonly grows in Eastern Europe, the Middle East, and Western Asia. Seeds of N. sativa are frequently used in folk medicine in Unani, Ayurveda, Chinese and Arabic system of medicine for the promotion of good health and the treatment of many ailments. It has great ancient medicinal value as carminative, stimulant, analgesic, anti-inflammatory and diuretic with many other uses. The Prophet Muhammad (Sallalaho Alaihi Wasallam) said “Black Cumin is the cure of all the diseases except Saam and “Saam is death”. (Narrated by Abu Huraira, Bukhari, Muslim, Ibn Maja, Masnad Ahmad). Study showed that the ethanol extract from N. sativa (EENS) significantly inhibited proliferation and colony formation and induced apoptosis in HeLa cells. The apoptotic induction was associated with the release of mitochondrial cytochrome c, increase of Bax/Bcl-2 ratio, activation of caspases-3, -9 and -8 and cleavage of poly (ADP-ribose) polymerase (PARP) (Ayman and Elkady, 2012). Study conducted for investigation of N. Sativa protective role in DAB induced liver carcinogenesis; the results showed that there was a significant change in the DNA content, histomorphology, and antioxidant enzymes in the liver tissues of the DAB treated group. These changes were restored to approximately the normal counterpart with Nigella sativa treatment, moreover it induce no harmful effects on the liver (Mohamed et al., 2010). Study showed the cytotoxic effect on Dalton’s lymphoma ascites cell grown in Swiss albino mice. Animal experiments indicated the retarded growth of ascites as compared to the controls with a longivity of 90% (Salomi and Panikkar, 1989). Thymoquinone (TQ), the most abundant constituent present in black seed, is a promising dietary chemopreventive agent and investigated against HCT-116 human colon cancer cells, TQ inhibits the growth of colon cancer cells which was correlated with G1 phase arrest of the cell cycle. TQ triggers apoptosis in a dose- and time-dependent manner. The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Study suggested that TQ has potential for the treatment of colon cancer (Hala et al., 2004). 2.17. Oroxylum indicum Family: Bignoniaceae Common name: Indian trumpet tree It is found throughout India in deciduous forests and moist areas. The roots are sweet, astringent, bitter, acrid, refrigerant, expectorant, carminative, anti-inflammatory and anti-microbial. The decoction of Oroxylum indicum bar could cure nasopharyngeal cancer. This is also used for curing gastric ulcer while the paste of the bark is applied to mouth for cancer, scabies, tonsil pain and other diseases (Mao, 2002). Methanolic extract of the fruit of Oroxylum indicum inhibited in vitro proliferation of HL-60 cells. The flavonoids baicalein was found to be an active component that induced apoptosis in HL-60 cell line (Roy et al. 2007). Methanolic crude extract of Oroxylum indicum is effective against Dalton’s lymphoma both in vitro and in vivo (Bijoy et al., 2011). Formulation prepared by different proportion of extracts of stem bark of O. indicum with Tecomella undulate, Buahinia variegate and leaves of Indigofera tinctoria (SJT ONC-1) showed significant cytotoxicity against human colon adenocarcinoma (Caco-2) and human breast adenocarcinoma (MCF-7) cell lines as compared to control, 63.82% for Caco-2 and 74.18% for MCF-7 cell lines (Savjiyani et al., 2012). Moreover, hot and cold non-polar extracts prepared in petroleum ether and chloroform was analyzed against MDA-MB-231 (human breast carcinoma), MCF-7 (human breast carcinoma) and WRL-68 (human liver embryonic) cell lines. Non-polar extract of O. indicum consequently possess effectual cytotoxicity and distinctive apoptosis-inducing abilities, along with evident anti-metastatic potentials (Naveen et al., 2012). Panax ginseng Family: Araliaceae Common name: Chinese ginseng, Asian ginseng P. ginseng is one of the best traditional herbal medicines used in Korea and China. The efficiency of ginseng has been demonstrated in the central nervous system and in the cardiovascular, endocrine, immune systems neoplastic, anti-stress and antioxidant activities. Panax ginseng has inhibiting effect on putative carcinogenesis mechanisms such as cell proliferation, apoptosis, immunosurveillance and angiogenesis (Shin et al., 2000). It was found that ginsenoside Rp1, a component of ginseng, inhibited breast cancer cell proliferation and inhibits both anchorage-dependent and independent breast cancer cell colony formation. A recent paper proposed an anti-inflammatory role of Panax ginseng in the sequence of progression to promotion in a model of carcinogenesis (Hofseth and Wargovich, 2007). Panax ginseng affects multiple points within the inflammatory cascade, including inhibition of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), and nuclear factor kappaB (NF-κB) (Keum et al., 2003; Friendl et al., 2001). Ginsenoside Rp1, reduces cancer cell proliferation through inhibition of the insulinlike growth factor 1 receptor (IGF-1R)/Akt pathway. Treatment with Rp1 inhibited breast cancer cell proliferation and inhibited both anchorage-dependent and -independent breast cancer cell colony formation. In addition, treatment with 20 μM Rp1 induced cycle arrest and apoptosis-mediated cell growth suppression. Rp1 decreased the stability of the IGF-1R protein in breast cancer cells (Kang et al., 2011). Rheum officinale Family: Polygonaceae Common name: Chinse rhubarb The roots of medicinal rhubarb have been used in traditional Chinese and Tiberan medicine. Generally it is spread to India, Russia, Europe and jaundice. It has been reported to have anti-tumor activity with hepatocarcinoma (Cao et al., 2005). It significantly inhibited the proliferation of Human lung adenocarcinoma A549 and Human breast carcinoma MCF-7 cells in vitro, confirmed by the cell viability and colony formation assays. Water extract treatment resulted in internucleosomal DNA cleavage in both A549 and MCf-7 cell lines, while the internucleosomal DNA from untreated cancer cells remained intact (Li et al., 2009). Treatment of gemcitabine combined with emodin, an anthraquinone derivatives from Rheum officinale, efficiently suppressed tumor growth in mice inoculated with pancreatic tumor cells. This treatment paradigm promoted apoptotic cell death and mitochondrial fragmentation. Furthermore, it reduced phosphorylated-Akt (p-Akt) level, NF-κB activation and Bcl-2/Bax ratio, increased caspase-9 and -3 activation, Cytochrome C (CytC) release occurred in combination therapy. Collectively, emodin enhanced the activity of gemcitabine in tumor growth suppression via inhibition of Akt and NF-κB activation, thus promoting the mitochondrial-dependent apoptotic pathway (Wei et al., 2011). Sansevieria roxburghiana Family: Dracanaceae Common name: Murva, Indian bowstring hemp It occurs in the Eastern coastal regions of India, also in Sri Lanka, Indonesia and tropical Africa (Eggli, 2002; Prakash, 2008). The whole plant is traditionally used as cardiotonic, expectorant, febrifuge, purgative, tonic, in granular enlargement and rheumatism (Dhilman, 2006; Pullaiah, 2006; Khare, 2007). There are reports that methanolic extract of leaves of S. roxburghiana showed a potent cytotoxicity activity against HepG2 liver cancer cell line. The concentration of leaf extract at 500µg/ml showed inhibition percentage with regard to cytotoxicity of 81.6%µg/ml, and at 250 µg/ml 70.8% as well as 57.3% at 125mci/ml. however, non-toxic to 3T3 cells but toxic to 50% HepG2 cells was recorded at a concentration to lesser than 100µg/ml (Deepa et al., 2011). Haldar et al. reported that aqueous ethanolic extract of S. roxburghiana rhizome at the doses of 50 and 100 mg/ kg significantly reduced the transplanatable murine tumor cells namely Ehrlich ascties carcinoma cells volume, packed cell volume, tumor cell count (viable and non-viable) and restored the hematological and serum biochemical parameters towards normal values (Pallab et al., 2010). Saxifrage stolonifera Family: Saxiferaceae Common name: Strawberry begonia It is native to Asia but has been introduced to other continents, mainly for use as an ornamental. Studies revealed that the extracts of S. stolonifera can inhibit proliferation of cancer cells in vitro by induction of apoptosis. Chen et al. studied the effect of extracts from S. stolonifera on human tumor cell lines BGC823 by MTT assay at concentrations ranging from 5 to 100 µM. They found that the inhibitory effects of b-sitotserol, gallic acid and quercetin were concentration dependent. Among these quercetin was found to exhibit high effect on BGC-823 cells, with the growth inhibition ratio of 39% after 72h treatment at 100µM, while the growth inhibition ratios of other compounds were considerably lower even at high concentration, ranging from 6.6% to 22.5% after 72h treatment at 100 µM (Cehn et al., 2008). Quercetin brought out morphological changes on the tumor cells and induced apoptosis on human promyelocytic leukemia cells (HL-60 cells) and kidney tubule epithelial cells (NRK-52E) (Shen et al., 2003). Solanum nigrum Family: Solanaceae Common name: Back nightshade, Makoi S. nigrum has a potent biological activity and has been extensively used in traditional medicine because of its diuretic and antipyretic effects. It is used in inflammation, edema, mastitis, cirrhosis of liver in oriental medicine (Jainu and Devi, 2006; Heo and Lim, 2004). It is generally found in native to Europe and Asia. Aqueous extract of S.nigrum berries have been studied against human breast cancer T47D cells, colon cancer RKO cells, and prostate cancer PC-3 cells. Aqueous extract of berries of Solanum nigrum caused inhibition of 44-79% in T47D cells at the concentrations ranging from 1.0 to 10% after 24 hours exposure and 31-76% inhibition of RKO cells moreover prostate cancer PC-3 cells demonstrated 59-85% inhibition at similar concentrations and time (Akbar et al., 2011). S. nigrum methanolic extract has significant cytotoxicity effect on HeLa Cell Line in concentration range between 10 mg/ml to 0.0196 mg/ml by using SRB assay and inhibitory action on HeLa cell line in concentration range between 10 mg/ml to 0.0196 mg/ml by using MTT assay, methanolic extract of these drugs showed greater activity on HeLa cell line and little activity on Vero cell line (Sanjay et al., 2009). Smilax glabra Family: Liliaceace Common name:Ba Qia, Jin Gang Teng It is commonly known as “Ba Qia” in the Chinese system of medicine and used for the treatment of rheumatic, arthritis, detoxification, lumbago, gout, and some inflammatory diseases (Ooi et al., 2008; Shao et al., 2007). Smilax sp. is distributed throughout the tropic and sub tropic parts of the world. It has been reported that treatment with rhizome against human breast carcinoma T47D cells at concentration of 1.0 to 10% aqueous extract demonstrated 3-21% cell growth inhibition after 24 hrs. In addition prostate cancer PC-3 cell exhibited inhibition of cell growth to 2-30% at similar dose and time. Moreover, the cell growth inhibition of human colon cancer RKO cell 6 to 26% has been reported with treatment using above plant. The effect of the aqueous extract was observed high at increased in time 24 to 72 hours (Akbar et al., 2011). Swertia chirayta Family: Gentinaceae Common name: Chirata, Kirata-tikta Found in temperate Himalayas and in hills of Meghalaya. It has multifarious therapeutic values and is widely used a crude drug. It possesses anti-helminthic, hypoglycemic, febrifuge, anti-malarial, antidiarrheal and antipyretic properties. Aqueous extract of Swertia chirayta (whole plant) exhibited 5-24% inhibition in human breast cancer cell T47D cells at 1.0 to10% concentration for 24 hours. Human colon cancer RKO cell inhibited to 8-28%, moreover, prostate cancer PC-3 cells exposed to S.chirayta exhibited 2-28% inhibition at similar doses for the 24 hour dosage [Akbar et al., 2011]. Withania somnifera Family: Solanaceae Common name: Ashwagandha W. somnifera is well known Ayurvedic plant and is found in throughout India, East Asia, and Africa. Historically, the plant has been used as an aphrodisiac, liver tonic, anti-inflammatory agent, astringent, and more recently to treat bronchitis, asthma, ulcers, emaciation, insomnia, and senile dementia. Clinical trials and animal research support the use of Ashwaganda for anxiety, cognitive and neurological disorders, fertility, inflammation, and Parkinson’s disease. Ashwaganda’s chemopreventive properties make it a potentially useful adjunct for patients undergoing radiation and chemotherapy. Ashwaganda is also used therapeutically as an adaptogen for patients with nervous exhaustion, insomnia, and debility due to stress, and as an immune stimulant in patients with low white blood cell counts. W. somnifera improves semen quality by regulating reproductive hormones (Mohammad et al., 2009). W. somnifera decreases NF-kB levels, suppresses intercellular tumor necrosis factor and potentiates apoptotic signaling in animal cancerous cell lines. In Vitro and In Vivo studies of W. somnifera showed stimulary effect on cytotoxic T lymphocyte generation and demonstrated the potential to reduce tumor growth (Davis and Kuttan, 2002). The chemopreventive effect of W. somnifera root extract was demonstrated in a study on induced skin cancer in Swiss albino mice. Withaferin A isolated from the extract showed significant antitumor and lacked any noticeable systemic toxicity. The chemopreventive effect of W. somnifera hydroalcoholic root extract (WSRE) on 7, 12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was investigated in Swiss albino mice. Results of the study revealed a significant decrease in incidence and average number of skin lesions in mice compared with DMBA alone at the end of Week 24 (Jai et al., 2002). The roots of W. somnifera consist primarily of compounds known as withanolides, which are believed to account for its extraordinary medicinal properties. Withanolides inhibit NF-kappaB activation induced by a variety of inflammatory and carcinogenic agents, including tumor necrosis factor (TNF), interleukin-1beta, doxorubicin, and cigarette smoke condensate, and also NF-kappaB-regulated gene expression which may explain the ability of withanolides to enhance apoptosis and inhibit invasion and osteoclastogenesis (Ichikawa et al., 2006). In vitro cytotoxicity in 50% ethanol extract of root, stem and leaves of W. somnifera report growth inhibitory importance against various human cancer cell lines of four different tissues i.e. PC-3, DU-145 (prostrate), HCT-15 (colon), A-549 (lung) and IMR-32 (neuroblastoma) (Yadav et al., 2010). These compounds of W. somnifera could provide a potential and relatively safe radiosensitizer or chemopreventive agent (Devi, 1996). Zingiber officinale Family: Zingiberaceae Common name: Adarak, ginger Z. officinale is cultivated commercially in India, China, South East Asia, West Indies and other part of the world. The British Herbal Compendium reported its actions as carminative, anti-ementic, spasmolytic, peripheral circulatory, stimulant, and anti-inflammatory. It is a natural dietary component with antioxidant and anticarcinogenic propertie. [6]-gingerol, a compound from ginger can inhibit angiogenesis of human endothelial cells and cause cell cycle arrest in the G1 phase through the down regulation of cyclin D1. Keum et al. found that [6]-paradol and other structurally related derivatives like [10]-paradol, [3]dehydroparadol, [6]-dehydroparadol and [10]-dehydroparadol, induced apoptosis in an oral squamous carcinoma cell line, in dose dependent manner through a caspase-3-dependent mechanism (Keum et al., 2002). Beta- Elemene is a novel anticancer drug; it triggers apoptosis in non-small cell lung cancer cells through a mitochondrial release of the cytochrome c- mediated apoptotic pathway (Wang et al., 2005). CONCLUSION As revealed in the most sacred book i.e. Quran in chapter ‘The Bee’ (16), verse no. 11 “With it He causes to grow for you the crops, the olives, the date-palms, the grapes and every kind of fruit. Verily! In this is indeed an evident proof and a manifest sign for people who give thought”. Thus plants are very beneficial for human beings and nature also. Plants are the largest sources for secondary metabolites and many bioactive compounds are responsible for their anticancer activity. This review evaluates their anticancerous property. Therefore exploration of their bioactive principles would be helpful in developing an anticancer drug, with potent therapeutic properties. References: Acharya D., Shivlingi: A common but important twinr in Patalkot. 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Botanical name Common name Family Part(s) used Artemisia vulgaris Artocarpus obtusus Azadirachta indica Bacopa monnieiri Beorhaavia diffusa Blumea balsamifera Bryonia laciniosa Compositae Moraceae Meliaceae Scrophularaiceae Nyctaginaceae Asteraceae Cucurbitacea Calotropis procera Cassia occidentalis Catharanthus roseus Cichorium intybus Mugwort Breadfruit Indian Neem Brahmi Punarnava, Snathikari Ngai camphor Shivlingi, Bryony, Snakeweed, Apple of Sodom, Aak Kasonda, coffee senna Madagascar periwinkle Chicory, Kasni Citrus maxima Dysoxylum binectiferum Emblica officinalis Pomelo Lasunni amari Amla Moringa oleifera Nigella sativa Oroxylum indicum Panax ginseng Horseradis,Sahijan Kalaunji, Black cumin Indian trumpet tree Asian ginseng, Chinese ginseng Chinse rhubarb Murva, Indian bowstring hemp Strawberry begonia Back nightshade, Makoi Ba Qia, Jin Gang Teng Chirata, Kirata-tikta Ashwagandha Adarak, Ginger Rheum officinale Sansevieria roxburghiana Saxifrage stolonifera Solanum nigrum Smilax glabra Swertia chirayta Withania somnifera Zingiber officinale References Inflorescence Stem bark Leaves Whole plant Leaves Leaves Leaves Method of preparation and Administration Aqueous extract, In-Vitro Different solvents, In-Vitro Ethanolic extract, In-Vitro, In-Vivo Different solvents, In-Vitro, In-Vivo 80% hydro-alcoholic, In- Vivo Ethanolic, In-Vitro Different solvents, In-Vitro Ascelpiadaceae Leguminoseae Apocynaceae Compositae or Asteraceae Rutaceae Meliaceae Euphorbiaceae Root, Latex, Stem Whole plant Leaves, Seeds Different solvents, In-Vitro, In-Vivo Different solvents, In-Vitro Different solvents, In-Vitro, In-Vivo Aqueous extract, In-Vitro 38-41 42 44-47 15 Leaves, Fruit Bark Whole plant 51, 52 53, 54 55-58 Moringaceae Ranunculaceae Bignoniaceae Araliaceae Leaves, fruit, seeds Seeds Fruit, bark Root Different solvents, In-Vitro, In-Vivo Methanolic extract, In-Vitro Ethanolic, aqueous extract, In-Vitro, In-Vivo Different solvents, In-Vitro, In-Vivo Ethanolic extract, In-Vitro, In-Vivo Different solvents, In- Vitro, In-Vivo Aqueous extract, In-Vitro Polygonaceae Dracanaceae Whole plant Leaves, rhizome Water extract, In-Vitro, In-Vivo Different solvents, In-Vitro, In-Vivo 77, 78 84, 85 Saxiferaceae Solanaceae Liliaceace Gentinaceae Solanaceae Zingiberaceae Whole plant Berries Rhizome Whole plant Root Rhizome Ethanolic extract, In-Vitro Aqueous, methanolic extract, In-Vitro Aqueous extract, In-Vitro Aqueous extract, In-Vitro Different solvents, In-Vitro, In-Vivo Synthetically modified, In-Vitro 86, 87 15, 90 15 15 94-98 99-100 Figure 1: Anticancerous phytochemicals isolated from medicinal plants. 15 23 26-28 29 30, 31 32 36 59-61 62-65 67-70 71-75