Download ANTICANCEROUS MEDICINAL PLANTS: A REVIEW Jamal Akhtar

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: [email protected]
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. American Chronicle 2007, Oct. 14.
Ahmed-Belkacem A., Macalou S., Borrelli F., Capasso R., Fattorusso E., Taglialatela-Scafati O.,
Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors. Journal
of Medicinal Chemistry 2007, 50, (8), 1933-1938.
Akbar Nawab, Mohammad Yunus, Abbas Ali Mahdi, Sanjay Gupta., Evaluation of Anticancer Properties
of Medicinal Plants from the Indian Sub-Continent. Molecular and Cellular Pharmacology 2011,
3, (1), 21-29.
Alpana S. Moghe, Sudha G. Gangal and Priya R. Shilkar., In Vitro cytotoxicity of Bryonia lociniosa
(Linn.) Naud. on human cancer cell lines. Indian Journal of Natural Products and Resources
2011, 2, (3), 322-329.
Ayman I. Elkady., Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human
cervical carcinoma HeLa cells. African Journal of Biotechnology 2012, 64, 12710-12720.
Bharli R., Azad M.R., Tabassum J., Chemopreventive action of Boerhaavia diffusa on DMBA- induced
skin carcinogenesis in mice. Indian Journal of Physiology and Pharmacology 2003, 47, 459-464.
Bijoy Brahma, Surya Bali Prasad, Akalesh Kumar Verma, Gabriel Rosangkima., Study on the antitumor
efficacy of some medicinal plants of Assam against murine ascites Dalton’s lymphoma.
Pharmacologyonline 2011, 3, 155-168.
Boonlaksiri C., Oonanant W., Kongsaeree P., Kittakoop P., Tanticharoen M., Thebtaranonth Y., An
antimalarial stilbene from Artocarpus integer. Phytochemistry 1992, 54, (4), 415–417.
Butler M S., Natural products to drugs: natural product-derived compounds in clinical trials. Natural
Product Reports 2008, 25, 475.
Cao Y.,Xia Q.H., Meng H., Zhong A.P., Antitumor and synergistic effect of Chinese medicine “bushen
huayu jiedu recipe” and chemotherapy on transplanted animal hepatocarcinoma. World journal of
Gastroenterology 2005, 11, 5218-5220.
Cehn Z., Liu Ym, Yang S., Song BN., Xu GF., Studies on the chemical constituents and anticancer
activity of Saxifera stolonifera (L) Meeb. Bioorganic and Medicinal Chemistry 2008, 16, (3),
1337-1344.
Choeden T., Mathan G., Arya S., Kumar VL., Kumar V., Anticancer and cytotoxic properties of the latex
of Calotropis procera in atransgenic mouse model of hepatocellular carcinoma. World Journal of
Gastroenterology 2006, 12, (16), 2517-2522.
Consolacion Y Ragasa, Ruel M. Levida, Ming-Jaw Don, Chien Chang Shen., Cytotoxic Isothiocyanates
from Moringa oleifera Lam Seeds. Philipine Science Letters 2012, 5, (1), 46-52.
Davis L., Kuttan G., Effect of Withania somnifera on CTL activity. Journal of Experimental and Clinical
Research 2002, 21, (1), 115-118.
Deepa Philip, Kaleena P.K., Valivittan K., In-Vitro cytotoxicity and anticancer activity of Sansevieria
roxburghiana. International Journal of Current Pharmaceutical Research 2011, 3, (3), 71-73.
Desai A.G., Qazi G.N., Ganju R.K., Medicinal plants and cancer chemoprevention. Current Drug
Metabolism 2008, 9, 581-591.
Devi PU., W. somnifera Dunal (Ashwagndha): potential plant source of a promising drug for cancer
chemotherapy and radiosensitization. Indian Journal of Experimental Biology 1996, 34, 927-932.
Dhiman AK., Ayurvedic Drug Plants. New Delhi, Dayal Publishing House 2006.
Eggli US., Illustrated Hand Book of Succulent Plants: Monocotyledons. Berlin, Heidelberg: Springer
2002.
El-Sayed A., Handy G.A., Cordell G.A., Catharanthus alkaloids. XXXVIII. Confirming structural
evidence and antineoplastic leurosine-N’b-oxide (pleurosine), roseadline and vindolicine from
Catharanthus roseus. Journal of Natural Products 1983, 46, 517-527.
Fauziah Othman, Gholamreza Motalleb, Sally Lam Tsuey Peng, Asmah Rahmat, Rusliza Basri, Chong
Pei Pei., Effect of Neem Leaf Extract (Azadirachta indica) on c-Myc Oncogene Expression in 4T1
Breast Cancer Cells of BALB/c Mice. Cell Journal 2012, 14, 1, 53-60.
Friedl R., Moeslinger T., Kopp B., Spieckermann P.G., Stimulation of nitric oxide synthesis by the
aqueous extract of Panax ginseng root in RAW 264.7 cells. British Journal of Pharmacology
2001, 134, 1663-1670.
Gabrielian S.E., and Gevorgovich A., Bryonia as novel plant adoptigen, for prevention and treatment of
stress induced disorders. Promising Research Abstracts PRA-5003, 1997, 1-8.
Guilford J.M., Pezzuto J.M., Natural products as inhibitors of carcinogenesis. Wexpert Opin Investig
Drugs 2008, 17, 1341-52.
Gupta R., Gabrielsen B., Ferguson S.M., Nature’s medicines: Traditional knowledge and intellectual
property management. Case studies from the National Institutes of Health (NIH) USA. Current
Drug Discovery Technology 2005, 2, 203.
Hala Gali-Muhtasib, Mona Diab-Assaf, Carsten Boltze, Josianne Al-Hmaira, Roland Hartig, Albert
Roessner, Regine Schneider-Stock., Thymoquinone extracted from black seed triggers apoptotic
cell death in human colorectal cancer cells via a p53-dependent mechanism. International Journal
of Oncology 2004, 25, (4), 857-866.
Haque R., Bin-Hafeez B., Ahmad I., Parvez S., Pandey S., Raisuddin S., Protective effect of
Emblica Officinalis Gaertn. In cyclophosphamide-treated mice. Human and
Experimental Toxicology 2001, 20, 643-650.
Harvey A L., Natural product in drug discovery. Drug Discovery Today 2008, 13, 894.
Hashim M.N., Rahmani M., Cheng Lian E.G., Sukari M.A, Yahuyu M., Antiproliferatiive Activity of
Xanthones Isolated from Artocarpus obtusus. Journal of Biomedcine and Biotechnology
2012,doi:10.1155/2012/130627.
Hemerson I F, Magalhes, Paulo M P, Ferreira, Eraldo S, Moura, Marcia R Torres, Ana P N N Alves,
Otilia D L Pessoa, Leticia V Costa-Lotufo, Manoel O Moraes, Cláudia Pessoa., In vitro and in
vivo antiproliferative activity of Calotropis procera stem extracts. Annals of the Brazilian
Academy of Sciences 2010, 82, (2), 407-416.
Heo KS, Lim KT., Antioxidative effects of glycoprotein isolated from Solanum nigrum L. Journal of
Medicinal Food 2004, 7, 349-57.
Hofseth L.J., Wargovich M.J., Inflammation, cancer, and targets of ginseng. Journal of Nutrition 2007,
137, 183S-185S.
Holland B.K., Prospecting for drugs in ancient texts. Nature 1994, 369, 702.
Ichikawa H., Takada Y., Shishodia S., Jayaprakasam B., Nair M.G., Aggarwal B.B., Withanolides
potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of
nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression.
Molecular Cancer Therapy 2006 5, (6), 1434-45.
Jai Prakash, Suresh Kumar Gupta, Amit Kumar Dinda., Withania somnifera Root Extract Prevents
DMBA-Induced Squamous Cell Carcinoma of Skin in Swiss Albino Mice. Nutrition and Cancer
2002, 42, (1), 91-97.
Jainu M., Devi C.S., Antiulcerogenic and ulcer healing effects of Solanum nigrum (L.) on experimental
ulcer models: possible mechanism for the inhibition of acid formation. Journal of
Ethnopharmacology 2006, 104, 156-63.
Johnson L S, Armstrong J.G., Gorman M., Burnett J.P., The vinca alkaloids: A new class of oncolytic
agents. Cancer Research 1963, 23, 1390-1427.
Jong T.T., Lin C.N., Shieh W.L., A pyranodihydrobenzoxanthone epoxide from Artocarpus communis.
Phytochemistry 1992, 31, (7), 2563–2564.
Jose J.K., Kuttan G., Kuttan R., 2001. Antitumour activity of Emblica officinalis. Journal of
Ethnopharmacology 75, 2-3, 65-9.
Kang J.H., Song K.H., Woo J.K., Park M.H., Rhee M.H., Choi C., Oh S.H., Ginsenoside Rp1 from Panax
ginseng exhibits anti-cancer activity by down-regulation of the IGF-1R/Akt pathway in breast
cancer cells. Plant Foods Human Nutrition 2011, 66, (3), 298-305.
Keum Y.S., Han S.S., Chun K.S., Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced
cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutation Research
2003, 523-524, 75-85.
Keum Y.S., Kim J., Lee K.H., Park K.K., Surh Y.J., Lee J.M., Induction of apoptosis and caspase-3
activation by chemoprevention [6]-paradol and structurally related compounds in KB cells.
Cancer Letters 2002, 177, 41-47.
Khan M.R., Omoloso A.D., Kihara M., Antibacterial activity of Artocarpus heterophyllus. Fitoterapia
2003, 74, (5), 501–505.
Khare C.P., Indian Medicinal Plants, an Illustrated Dictionary. Berlin, Heidelberg, Springer 2007.
Kirtikar K.R., and Basu B.D., Indian Medicical Plants, vol II, 2nd ed. Dehara Dun Publew Delhi 1987,
1158-1159.
Koehn F.E., Carter G.T., The evolving role of natural products in drug discovery. Nat Rev Drug
Discovery 2005, 4, 206.
Krishnaswamy K., Traditional Indian spices and their health significance. Asia Pacific Journal Clinical
Nutrition 2008, 17, 265-8.
Kumar V.L., Arya S., 2006. Medicinal uses and pharmacological properties of Calotropis procera. In:
Govil JN, editor. Recent Progress in Medicinal Plants. 11th vol Texas: Studium Press 2006, 373388.
KunduSen S., Gupta M., Mazumder U.K., Haldar P.K., Saha P., Bala A., 2011. Antitumor activity of
citrus maxima (Burm.) Merr. Leaves in Ehrlich’s Ascites Carcinoma Cell-Treated Mice.
International Scholarly Research Network Pharmacology 2011, doi:10.5402/2011/13873.
Lakshmi V., Agarwal S.K., Ansari J.A., Mahdi A.A., Rohitukine as a potent insecticidal and pesticidal
from Dyspxylum binectiferum. Natural Product: An Indian Journal 2012, 8, (3), 103-106.
Li W.Y., Chan S.W., Guo D.J., Chunga M.K., Leunga T.Y., Yua PHF., Water extract of Rheum officinale
Baill. Induces apoptosis in human lung adenocarcinoma A549 and human breast cancer MCF-7
cell lines. Journal of Ethnopharmacology 2009, 124, 251-256.
Lim HK, Moon JY, Prakash B, Kim H, Cho M, Cho SK., Induction of apoptosis in U937 human leukemia
cells by the hexane fraction of an extract of immature Citurs grandis Obseck fruits. Food
chemistry 2009, 114, 1245-1250.
Lizzy K.S., Narashima Rao, P L Puttaswamy T L., Chemotherapy of bacterial infections. Part 4: potential
anticholera agents. Indian Journal of Experimental Biology 1968, 6, (3), 168–169.
Madhulika Bhagat and Ajit Kumar Saxena., Evaluation of Cassia occidentalis for in vitro cytotoxicity
against human cancer cell lines and antibacterial activity. Indian Journal of Pharmacology 2010,
42, (4), 234–237.
Manal Mohamed Elhassan Taha, Siddig Ibrahin Abdel Wahab, Fauziah Othman, Parichehr Hanachi,
Ahmad Bustamam Abdul, Adel Sharaf Al-Zubari., In vivo Anti-tumor effects of Azadirachta
indica in Rat Liver Cancer. Research Journal of Biological Sciences 2009, 4, (1), 48-53.
Mao A.A., Oroxylum Indicum Vent.- a potential anticancer medicinal plant. Journal of Traditional
Knowledge 2002, 1, (1), 17-21.
Mehta R.G., Murillo G., Naithani R., Peng X., Cancer chemoprevention by natural products: how far have
we come? Pharmaceutical Research 2010, 27, 950-61.
Mohamed H.A., El-Sayed I.H., Moawad M., Protective effect of Nigella sativia seeds against
dimethylaminoazobenzene (DAB) induced liver carcinogenesis. Nature and Science 2010, 8, (6),
80-87.
Mohammad Kaleem Ahmad, Abbas Ali Mahdi, Kamla Kant Shukla, Najmul Islam, Singh Rajender,
Dama Madhukar, Satya Narain Shankhwar, and Sohail Ahmad., Withania somnifera improves
semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of
infertile males. Fertility and Sterility 2009, doi:10.1016/j.fertnstert.2009.04.046.
Mohana Kumara P., Zuehlke S., Priti V., Ramesha B.T., Shweta S., Ravikanth G., Vasudeva R.,
Santhoshkumar T.R., Spiteller M., Uma Shaanker R., Fusarium proliferatum, an endophytic
fungus from Dysoxylum binectariferum Hook.f, produces rohitukine, a chromane alkaloid
possessing anti-cancer activity. Antonie Van Leeuwenhoek 2012, 101, (2), 323-9.
Nair S., Varalakshmi K.N., Anticancer, cytotoxic potential of Moring oleifera extracts on HeLa cell lines.
Journal of Natural Pharmaceuticals 2011, 2, (3), 138-142.
Naveen Kumar D.R., Cijo George V., Suresh P.K., Ashok Kumar R., Cytotoxicity, Apoptosis Induction
and Anti-Metastatic Potential of Oroxylum indicum in Human Breast Cancer Cells. Asian Pacific
Journal of Cancer Prevention 2012, 13, (6), 2729-2734.
Ontengco D.C., Dayap L.A., Capal T.V., 1995. Screening for the antibacterial activity of essential oils
from some Philippine plants. Acta Manilana 1995, 43, 19–23.
Ooi L.S., Wong E.Y., Chiu L.C., Sun S.S., Ooi V.E., Antiviral and anti-proliferative glycoproteins from
the rhizome of Smilax glabra Roxb (Liliaceae). American Journal of Chinese Medicine 2008, 36,
185-95.
Pallab Kanti Haldar, Biswakanth Kar, Asis Bala, Sanjib Bhattacharya, Upal Kanti Mazumder., Antitumor
activity of Sanseviera roxburgahiana rhizome against Ehrlich ascites carcinoma in mice.
Pharmaceutical Biology 2010, 48, (12), 1337-1343.
Parida M.M., Upadhyay C., Pandya G., Jana A.M., Inhibitory potential of neem (A. indica Juss) leaves on
Dengue virus type-2 replication. Journal of Ethnopharmacology 2002 79, 273-278.
Patil A.D., Freyer A.J., Killmer L., A new dimeric dihydrochalcone and a new prenylated flavone from
the bud covers of Artocarpus altilis: potent inhibitors of cathepsin K. Journal of Natural Products
2002, 65, (4), 624–627.
Patwardhan B., Mashelkar R.A., Traditional medicine inspired approaches to drug discovery: can
Ayurveda show the way forwards? Drug Discovery Today 2009, 14, 804.
Patwardhan B., Vaidya, ADB., Chloghade M., Ayurveda and natural products drug discovery. Current
Science 2004, 86, 10.
Patwardhan B., 2000. Ayurveda: The ‘Designer’ medicine: A review of ethnopharmacology and
bioprospecting research. Indian Drugs 2000, 37, 14.
Patwardhan B., Traditional Medicine: Modern Approach For Affordable Global Health. In: Commission
on Intellectual Property Rights IaPHC, [World Health Organization (WHO)] 2005.
Prakash J.W., Raja R.D.A., Anderson N.A., Williams C., Regini G.S., Bensar K., Jajeev R., Kirula S.,
Jeeva S., Das S.C.M., Ethnomedicinal plants used by Kani tribes of Agastiyarmalai biosphere
reserve, Southern Western Ghats. Indian Journa of Traditional Knowledge 2008, 7, 410–413.
Prakash N.S., Sundaram R., Mitra S.K., In Vitro and In Vivo Anticancer Activity of Bacoside A from
Whole Plant of Bacopa Monieeiri (Linn). American Journal of Pharmacology and Toxicology
2011, 6, 1, 11-19.
Pullaiah T., Encyclopedia of World Medicinal Plants. Vol. V. New Delhi, Regency Publications 2006.
Purwal L., Pathak A.K., Jain U.K., In Vivo anticancer activity of the leaves and fruits of Moringa oleifera
on mouse melanoma. Pharmacologyonline 2010, 1, 655-665.
Rajani Mathur, Suresh K Gupta, Sandeep R Mathur, Thirumurthy Velpandian., Antitumor studies with
extracts of Calotropis procera (Ait.) R. Br. Root employing Hep2 cells and their possible
mechanism of action. Indian journal of Expeimental Biology 2009, 47, 343-348.
Roy M.K., Nakahara K., Na Thalang V., Trakoontivakom G., Takenaka M., Isobe S., Baicalein, a
flavanoid extracted from Methanolic extract of Oroxylum indicum inhibits proliferation of a cancer
cell line in vitro via induction of apoptosis. Die Pharmazie- An International Journal of
Pharmaceutical Science 2007, 62, (2), 149-153.
Saewan N., Koysomboom S., Chantrapromma K., Anti-tyrosinase and anticancer activities of flavonoids
from Blumea Balsamifera DC. Journal of Medicinal plants Research 2011, 5, (6), 018-1025.
Salomi M.J., Panikkar K.R., Anti-cancer activity of nigella sativa. Ancient Science of Life 1989, Vol.
VIII, Nos. 3&4, 262-266.
Sanjay Patel, Nirav Gheewala, Ashok Suthar, Anand Shah., 2009. In-Vitro cytotoxicity activity of
Solanum nigrum extract against hela cell line and vero cell line. International Journal of
Pharmacy and Pharmaceutical Sciences 2009, 1, (1), 38-46.
Saswati Mahapatra, R Jeffrey Karnes, Michael W Holmes, Charles Y F Young, John C Cheville, Manish
Kohli, Eric W Klee, Donald J Tindall, Krishna Vanaja Donkena., Novel Molecular Targets of
Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer. The AAPS
Journal 2011, 13, (3), 365-377.
Satish K Verma, Asima Shaban, Rajesh Nautiyal, Reena Purohit, Santosh Singh, Madhvi Lata Chimata.,
In Vitro cytotoxicity of Emblica Officinalis against different human cancer cell lines. Asian
Journal of Pharmaceutical and Clinical Research 2012, 5, 2, 77-78.
Savjiyani J.V., Dave H., Trivedi S., Rachchh M.A., Gokani R.H., 2012. Evaluation of anticancer activity
of polyherbal formulation. International Journal of Cancer Research 8, (1), 27-36.
Schaffer S., Schmitt-Schillig S, Müller WE, Eckert G.P., 2005. Antioxidant properties of Mediterranean
food plant extracts: geographical differences. Journal of Physiology Pharmacology 2005, 56, 11524.
Seyed Ahmad Emami, Nasser Vahdati-Mashhadian, Remisa Vosough, Mohammad Bagher Oghazian.,
The Anticancer Activity of Five Species of Artemisia on Hep2 and HepG2 Cell Lines.
Pharmacologyonline 2009, 3, 327-339.
Shao B., Guo H.Z., Cui Y.J., Simultaneous determination of six major stilbenes and flavonoids in Smilax
china by high performance liquid chromatography. Journal Pharm Biomed Anal 2007, 44, 737-42.
Shen S.C., Chen Y.C., Hsu F.L., Lee W.R., 2003. Differential apoptosis-inducing effect of quercetin and
its glycosides in human promyeloleukemia HL-60 cells by alternative activation of the caspase 3
cascade. Journal of Cellular Biochemistry 2003, 89, (5), 1044-1055.
Shin H.R., Kim J.Y., Yun T.K., Morgan G., Vainio H., The cancer- preventive potential of Panax
ginseng: a review of human and experimental evidence. Cancer Causes and Control 2000, 11,
565-576.
Siddiqui M.J., Ismail Z., Aisha A.F.A., Abdul Majid A.M.S., Cytotoxic Activity of Catharanthus roseus
(Apocynaceae) Crude Extracts and Pur Compounds Against Colorectal Cell Line. International
Journal of Pharmacology 2010, 6, 1, 43-47.
Soobrattee M.A., Bahorun T., Aruoma O.I., Chemopreventive actions of polyphenolic compounds in
cancer. Biofactors 2006, 27, 19-35.
Su B.N., Cuendet M., Hawthorne M.E., Constituents of the bark and twigs of Artocarpus dadah with
cyclooxygenase inhibitory activity. Journal of Natural Products 2002, 65, 2, 163–169.
Subapriya R., Bhuvaneswari V., Nagini S., Ethanolic Neem (Azadirachta indica) Leaf Extract Induces
Apoptosis in the Hamster Buccal Pouch Carcinogenesis Model by Modulation of Bcl-2, Bim,
Caspase 8 and Caspase 3. Asian Pacific Journal of Cancer Prevention 2005, 6, 515-520.
Şüra Baykan Erel, Serdar Gökhan Şenol, Fadime Aydin Köse, Petek Ballar., In Vitro cytotoxic properties
of six Artemisia L. Species. Turk Journal Pharmaceuticals Science 2011, 8, (3), 247-252.
Taylor W.L., Farnsworth N.R., The Catharanthus Alkaloids: Botany, Chemistry, Pharmacology and
Clinical Use. Ist Edn., Marcel Dekker Inc., New York, USA. 1975
Tousch D., Lajoix A.D., Hosy E., Chicoric acid, a new compound able to enhance insulin release and
glucose uptake. Biochem Biophys Research Communication 2008, 377, 131-5.
Ueda J.Y., Tezuka Y., Banskota A.H., Le Tran Q., Tran Q.K., Antiproliferative activity of Vietnamese
medicinal plants. Biol Pharm Bull 2002, 25, 753-760.
Van Quaduebeke E., Simon G., Andre A., DEwelle J., Yazidi M.E., Bruyneel F., Identification of a novel
cardenolide (2’’-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel
derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure
activity relationship analyses. Journal of Medicinal Chemistry 2005, 48, 849-856.
Wang G., Li X., Huang F., Zhao J., Ding H., Cunnuingham C., Antitumor effect of b- elemene in nonsmall-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptopic cell death.
Cellular and Molecular Life Sciences 2005, 62, 881-893.
Wei-Τian Wei, Hui Chen, Zhong-Lin Ni, Hai-Βin Liu, Hong-Fei Tong, Ling Fan, An Liu, Mai-Χuan Qiu,
Dian-Lei Liu, Hong-Chun Guo, Zhao-Hong Wang, Sheng-Zhang Lin., 2011 Antitumor and
apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale
Baill, against pancreatic cancer in mice via inhibition of Akt activation. International Journal of
Oncology 2011, 39, (6), 1381-1390.
Yadav B., Bajaj A., Saxena M., Saxena A.K., 2010. In Vitro Anticancer Activity of the Root, Stem and
Leaves of Withania Somnifera against Various Human Cancer Cell Lines. Indian J Pharm Science
2010, 72, (5), 659–663.
Table 1: List of medicinal plants traditionally used in the management of cancer.
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