Natural Herbs as Anticancer Drugs

Abstract

This article has been made to review some medicinal plants used for the treating cancer disease . The plant sources of India are likely to provide effective anticancer agents. Herbs have a vital role in the prevention and treatment of cancer. Examples are provided in this review of promising bioactive compounds obtained from various plants with medicinal and other therapeutic uses. The photochemical exploration of these herbs has contributed to some extent in this race for the discovery of new anticancer drugs. In recent years owing to the fear of side effects people prefer to use of natural plant products for cancer treatment. This review also helps to summarize the diverse methodologies and various ways to evaluate the potential natural compounds having anticancer activity. Although drug discovery from medicinal plants continues to provide an important source of new drug leads, numerous challenges are encountered including the procurement of plant materials and their selection.

Full text

International Journal of PharmTech Research
CODEN (USA): IJPRIF ISSN : 0974-4304
Vol.4, No.3, pp 1142-1153, July-Sept 2012
Natural Herbs as Anticancer Drugs
Nidhi Agarwal1* ,Chandana Majee1, G. S. Chakraborthy1
1Department of Pharmaceutical Technology, Noida Institute of Engineering
&Technology, 19, Knowledege Park-II, Greater Noida, Uttar Pradesh-201 306, India
*Corres Author: nidhinov07@gmail.com
Phone No: +919411824781
Abstract: This article has been made to review some medicinal plants used for the treating cancer disease .
The plant sources of India are likely to provide effective anticancer agents. Herbs have a vital role in the
prevention and treatment of cancer. Examples are provided in this review of promising bioactive compounds
obtained from various plants with medicinal and other therapeutic uses. The photochemical exploration of these
herbs has contributed to some extent in this race for the discovery of new anticancer drugs. In recent years
owing to the fear of side effects people prefer to use of natural plant products for cancer treatment. This review
also helps to summarize the diverse methodologies and various ways to evaluate the potential natural
compounds having anticancer activity. Although drug discovery from medicinal plants continues to provide an
important source of new drug leads, numerous challenges are encountered including the procurement of plant
materials and their selection.
Keywords: Medicinal plants, Anticancer agents, Bioactive compounds.
Introduction
Cancer is a leading cause of mortality, and it strikes
more than one-third of the world’s population and
it’s the cause of more than 20% of all deaths.
Among the causes for cancer are tobacco , viral
infection, chemicals, radiation, environmental
factors, and dietary factors.1Surgery, chemotherapy
and radiotherapy are the main conventional cancer
treatment often supplemented by other
complementary and alternative therapies in China.2
Plants has been used as an age old remedy of cancer
history of use in the treatment of cancer. Extensive
research at Sandoz laboratories in Switzerland in the
1960s and 1970s led to the development of
etoposide and teniposide as clinically effective
agents which are used in the treatment of
lymphomas, bronchial and testicular cancer.3These
plants may promote host resistance against infection
by re-stabilizing body equilibrium and conditioning
the body tissues. Several reports describe that the
anticancer activity of medicinal plants is due to the
presence of antioxidants present in them. In fact, the
medicinal plants are easily available, cheaper and
possess no toxicity as compared to the modern
(allopathic) drugs.4The development of novel plant-
derived natural products and their analogs for
anticancer activity details efforts to synthesize new
derivatives based on bioactivity- and mechanism of
action-directed isolation and characterization
coupled with rational drug design - based
modification.5
Oncogenes are regulators of cellular communication
with the outside environment. They are derived
through the mutation of proto-oncogenes. Mutated
oncogenes are stimulated by exposure to chemical,
environment or viral carcinogens, which leads to cell
changes and they produce proteins which are
either wrongly expressed within their normal cell or
expressed in inappropriate tissue which leads to
cellular proliferation and there by result in cancer
formation . Tumor suppressor genes are intended to
keep oncogenes in check by halting uncontrolled

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1143
cellular growth. In direct opposition to oncogenes,
which induce cancer when stimulated or amplified,
tumor suppressor genes promote cancer when
inactivated or attenuated. Two of the most prevalent
tumor suppressor genes involved in the generation of
cancer are p53 and retinoblastoma or Rb.6
Anticancer Plants
Acronychia Bauer:-Utilizing a differential extraction
technique for the examination of the bark of the
Australian plant Acronychia Baueri Schott
(Bauerella australiana Borzi), has resulted in the
isolation of the triterpene lupeol and the alkaloids
melicopine, acronycine, and normelicopidine. The
experimental anti tumor activity associated with the
crude alkaloidal mixture obtained from the ether
extract has been shown to be attributable to
acronycine. Experimental evidence is herein given,
showing acronycine to have the broadest antitumor
spectrum of any alkaloid isolated to date in these
laboratories. By virtue of its being chemically
unrelated to any of the presently utilized antitumor
agents it represents a new lead in the search for
agents effective in the chemotherapeutic
management of human neoplasms.7
Garlic (Allium sativum L.) has a long history of
being as a food having a unique taste and odor
along with some medicinal qualities. Modern
scientific research has revealed that the wide variety
of dietary and medicinal functions of garlic can be
attributed to the sulfur compounds present in or
generated from garlic. Although garlic produces
more than 20 kinds of sulfide compounds from a few
sulfur-containing amino acids, their functions are
different from one another; e.g., allicin, methyl allyl
trisulfide, and diallyl trisulfide have antibacterial,
antithrombotic, and anticancer activities,
respectively.8
Garlic [Allium sativum] is among the oldest of all
cultivated plants. It has been used as a medicinal
agent for thousands of years. It is a remarkable plant,
which has multiple beneficial effects such as
antimicrobial, antithrombotic, hypolipidemic,
antiarthritic, hypoglycemic and antitumor activity. A
number of studies have demonstrated the
chemopreventive activity of garlic by using different
garlic preparations including fresh garlic extract,
aged garlic, garlic oil and a number of organosulfur
compounds derived from garlic. The
chemopreventive activity has been attributed to the
presence of organosulfur compounds in garlic.
However it not understood, but several mode of
action this is achieved is not fully understood, but
several modes of action have been proposed. These
include its effect on drug metabolizing enzymes,
antioxidant properties and tumor growth inhibition.
Most of these studies were carried out in the animal
models. Also, recent research has been focused on
the antimutagenic activity of garlic. Recently, it has
been observed that aged garlic extract, but not the
fresh garlic extract, exhibited free radical
scavenging activity. The two major compounds in
aged garlic, S-allylcysteine and S-allylmercapto-L-
cysteine, which has had the highest radical
scavenging activity. In addition, some organosulfur
compounds derived from garlic, include S-
allylcysteine, have been found to retard the growth
of chemically induced and transplantable tumors in
several animal models. Therefore, the consumption
of garlic may provide some kind of protection from
cancer development.9
Table No.1:Types of cancer and common oncogenic or tumor suppressor gene origin .
Cancer type
Common oncogenic or tumor suppressor
gene origin
Chronic myelogenous leukemia
Bcr-abl proto-oncogene translocation
Follicular lymphoma
Bcl-2 amplification, myc mutation
Sporadic thyroid cancer
Ret mutation
Colorectal and gastric cancer
APC gene mutation
Familial breast and ovarian cancer
BRCA1, BRCA2 mutation
Invasive ductal breast cancer
HER-2 amplification
Familial melanoma
P16INK4A mutation
Childhood neuroblastoma and small cell lung
cancer
N-myc amplification
Leukemia, breast, colon, gastric and lung
cancer
c-MYC amplification
Renal cell cancer
Von Hippel-Lindaugene (VHL) dysfunction

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Artemisia capillaries is a major important food and
medicinal resource found in Korea. In order to
confirm the biological activities of Artemisia
capillaries, antioxidant and anticancer activities
from in vitro assays were investigated. The
Artemisia capillaries methanol (MeOH) extracts
were used for the evaluation of DPPH(2,2-diphenyl-
1-picrylhydrazyl) scavenging, total phenolic content,
total flavonoid content, hydroxyl radical (ㆍOH)
scavenging, reducing power assay as antioxidant
activity, as well as anticancer activities as MTT
assay. As a result, the Artemisia capillaries MeOH
extracts showed potent antioxidative activity and
anticancer activity in vitro. These results suggest
that the Artemisia capillaries MeOH extracts have a
potential alleviated oxidation process, cell motility
activity, and tumorigenesis. 10
Astragalus membranaceus, a commonly used
Chinese medicinal plant, has been shown to be
capable of restoring the impaired T cell functions in
cancer patients. The in vitro and in vivo anti-tumor
effects of A. membranaceus were investigated. Five
bioactive fractions were isolated from the root of A.
membranaceus, the fraction designated as AI was
found to be the most potent among the five fractions
with respect to its mitogenicity on murine
splenocytes. Besides investigating the cytostatic
effect of AI, its activities on macrophage function,
tumor necrosis factor production, induction of
lymphokine-activated killer cell and tumor cell
differentiation were also examined. The
macrophage-like tumors and the myeloid tumors
were found to be more sensitive to the cytostatic
activity of AI, whereas the fibroblast-like tumors
and the mouse Ehrlich ascites tumor appeared to be
relatively resistant. Moreover, AI could effectively
suppress the in vivo growth of syngeneic tumor in
mice. Results showed that murine macrophage
pretreated with AI had increased in vitro and in vivo
cytostatic activities towards MBL-2 tumor. AI could
also act as a priming agent for tumor necrosis factor
production in tumor-bearing mice. Preincubation of
mouse splenocytes with AI could induce in vitro
lymphokine-activated killer-like activity towards
WEHI-164 cell. Furthermore, AI was able to induce
monocytic differentiation of both human and murine
cells in vitro. AI administered in vivo could even
partially restore the depressed mitogenic response in
tumor-bearing mice. Collectively, the results showed
that A. membranaceus could exhibit both in vitro
and in vivo anti-tumor effects, which might be
achieved through activating the anti-tumor immune
mechanism of the host.11
The in vitro inhibitory effect of Beta vulgaris (beet)
root extract on Epstein-Barr virus early antigen
(EBV-EA) induction using Raji cells revealed a high
order of activity compared to capsanthin, cranberry,
red onion skin and short and long red bell peppers.
An in vivo anti-tumor promoting activity evaluation
against the mice skin and lung bioassays also
revealed a significant tumor inhibitory effect. The
combined findings suggest that beetroot ingestion
can be one of the useful means to prevent cancer. 12
Green tea is an aqueous infusion of dried
unfermented leaves of Camellia sinensis (Family
Theaceae) from which numerous biological
activities have been reported including
antimutagenic, antibacterial, hypocholesterolemic,
antioxidant, antitumor and cancer preventive
activities. From the aqueous-alcoholic extract of
green tea leaves, six compounds (+)-gallocatechin
(GC), (-)-epicatechin (EC), (-)-epigallocatechin
(EGC), (-)-epicatechin gallate (ECG), (-)-
epigallocatechin gallate (EGCG) and caffeine, were
isolated and purified. Together with (+)-catechin,
these compounds were tested against each of four
human tumor cells lines (MCF-7 breast carcinoma,
HT-29 colon carcinoma, A-427 lung carcinoma and
UACC-375 melanoma). The three most potent green
tea components against all four tumor cell lines were
EGCG, GC and EGC. EGCG was the most potent of
the seven green tea components against three out of
the four cell lines (i.e. MCF-7 breast cancer, HT-29
colon cancer and UACC-375 melanoma). On the
basis of these extensive in vitro studies, it would be
of considerable interest to evaluate all three of these
components in comparative preclinical in vivo
animal tumor model systems before final decisions
are made concerning which of these potential
chemopreventive drugs should be taken into broad
clinical trials. 13
Camptothecin (CPT) is an anticancer and antiviral
alkaloid produced by the Chinese tree Camptotheca
acuminata (Nyssaceae) and some other species
belonging to the families Apocynaceae, Olacaceae,
and Rubiaceae. Bark and seeds are currently used as
sources for the drug. Several attempts have been
made to produce CPT from cell suspensions;
however, the low yields obtained limit this approach.
Cultures of differentiated cell types may be an
alternative source of alkaloid production. Hairy root
cultures of C. acuminata were established from
tissue transformed with Agrobacterium rhizogenes
strains ATCC 15834 and R-1000. Integration of
these genes are responsible for the hairy-root
phenotype (rol genes) into the plant genome was
verified by DNA gel blot analysis. The hairy roots
produce and secrete CPT as well as the more potent
and less toxic natural derivative, 10-
hydroxycamptothecin (HCPT), into the medium.
Remarkably, the cultures were able to synthesize the

Nidhi Agarwal et al /Int.J.PharmTech Res.2012,4(3)
1145
alkaloids at levels equal to, and sometimes greater
than, the roots in planta, i.e., 1.0 and 0.15 mg/g dry
weight for CPT and the HCPT, respectively.14
Catharanthus roseus produces low levels of two
dimeric terpenoid indole alkaloids, vinblastine and
vincristine, which are widely used in cancer
chemotherapy. The dimerization reaction leading to
α-3', 4’-anhydrovinblastine is a key regulatory step
for the production of the anticancer alkaloids in
planta has an potential application in the industrial
production of two semisynthetic derivatives also
used as anticancer drugs. The cloning,
characterization, and subcellular localization of an
enzyme with anhydrovinblastine synthase activity
identified as the major class III peroxidase present in
C. roseus leaves and was named an CrPrx1. The
deduced amino acid sequence corresponds to a
polypeptide of 363 amino acids including an N-
terminal signal peptide showing the secretory nature
of CrPrx1. CrPrx1 has a two-intron structure and is
present as a single gene copy. Phylogenetic analysis
indicates that CrPrx1 belongs to an evolutionary
branch of vacuolar class III peroxidases whose
members seem to have been recruited for different
functions during evolution. Expression of a green
fluorescent protein-CrPrx1 fusion confirmed the
vacuolar localization of this peroxidase, the exact
subcellular localization of the alkaloid monomeric
precursors and dimeric products. Expression data
further supports the role of CrPrx1 in α-3', 4’-
anhydrovinblastine biosynthesis, indicating the
potential of CrPrx1 as a target to increase alkaloid
levels in the plant.15
Inonotus obliquus :-The Chaga mushroom (Inonotus
obliquus) has been used in folk medicine to treat
cancers. However, limited information exists on the
underlying anticancer effects of the major
component of I. obliquus in vivo studies . It is
hypothesized that the pure compounds (3β-hydroxy-
lanosta-8, 24-dien-21-al, inotodiol and lanosterol,
respectively) isolated from I. obliquus would inhibit
tumor growth in Balbc mice bearing Sarcoma-180
cells (S-180) in vivo and growth of human
carcinoma cells in vitro. To test this hypothesis, the
growth inhibition of each subfraction isolated from
I. obliquus on human carcinoma cell lines (lung
carcinoma A-549 cells, stomach adenocarcinoma
AGS cells, breast adenocarcinoma MCF-7 cells, and
cervical adenocarcinoma HeLa cells) was tested in
vitro. Then, after S-180 implantation, the mice were
fed a normal chow supplemented with 0, 0.1 or 0.2
mg of subfraction 1, 2 or 3 per mouse per day. All of
the subfractions isolated from I. obliquus showed
significant cytotoxic activity against the selected
cancer cell lines in vitro. Subfraction 1 was more
active than subfraction 2 and subfraction 3 against
the A549, AGS and MCF-7 cancer cell lines in vitro.
In in vivo results, subfraction 1 isolated from I.
obliquus at concentrations of 0.1 and 0.2 mg/mouse
per day significantly decreased tumor volume by
23.96% and 33.71%, respectively, as compared with
the control. Subfractions 2 and 3 also significantly
inhibited tumor growth in mice bearing S-180 as
compared with the control mouse tumor. Subfraction
1 isolated from I. obliquus showed greater inhibition
of tumor growth than subfractions 2 and 3, which
agrees well with the in vitro results. The results
suggest that I. obliquus and its compounds in these
subfractions isolated from I. obliquus could be used
as natural anticancer ingredients in the food and/or
pharmaceutical industry.16
Anticancer activity of the rhizomes of turmeric
(Curcuma longa) was evaluated by italies in vitro
using tissue culture methods and in vivo in mice
using Dalton's lymphoma cells grown as ascites
form. Turmeric extract inhibited the cell growth in
Chinese Hamster Ovary (CHO) cells at a
concentration of 0.4 mg/ml and was cytotoxic to
lymphocytes and Dalton's lymphoma cells at the
same concentration. Cytotoxic effect was found
within 30 min at room temperature (30 C). The
active constituent was found to be 'curcumin' which
showed cytotoxicity to lymphocytes and Dalton's
lymphoma cells at a concentration of 4 mg/ml.
Initial experiments indicated that turmeric extract
and curcumin reduced the development of animal
tumours.17
Curcuma zedoaria belonging to the family
Zingiberaceae has been used in the traditional
system of medicine in India and Southwest Asia in
treating many human ailments and is found to
possess many biological activities. The rationale of
the present study was to isolate, identify, and
characterize antitumour principles from the rhizomes
of Curcuma zedoaria, to assess its cytotoxic effects
on human and murine cancer cells, to determine its
apoptosis inducing capacity in cancer cells, and to
evaluate its tumour reducing properties in in vivo
mice models. Isocurcumenol was characterized as
the active compound by spectroscopy and was found
to inhibit the proliferation of cancer cells without
inducing significant toxicity to the normal cells.
Fluorescent staining exhibited the morphological
features of apoptosis in the compound-treated cancer
cells. In vivo tumour reduction studies revealed that
a dose of 35.7mg/kg body weight significantly
reduced the ascitic tumour in DLA-challenged mice
and increased the lifespan with respect to untreated
control mice.18
Three constituents, β-sitosterol, laserine and
epilaserine, were isolated from the lipophilic fraction
of Daucus carota. Among the 3 constituents,

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epilaserine showed significantly inhibitory effect on
leukemia cell, HL-60.19
Licochalcone (LA) is a novel estrogenic flavonoid
isolated from PC-SPES composition herb licorice
root (Glycyrrhiza Glabra) which show significant
antitumor activity in various malignant human cell
lines. To better understand its anti-Cancer activities
investigation were carried out in LA-elicited growth
control and induction of apoptosis using androgen-
independent p53-null PC-3 prostate cancer cells. LA
induced modest level of apoptosis but had more
pronounced effect on cell cycle progression arresting
cells in G2/M, accompanied by suppression of
cyclin B1 and cdc2. It also inhibited phosphorylation
of Rb, specifically phosphorylation of S780 with no
change of phosphorylation status of T821, decreased
expression of transcription factor E2F concurrent
with reduction of cyclin D1, down-regulation of
CDKs 4 and 6, but increased cyclin E expression.
These findings provide mechanistic explanation for
LA activity and suggest that it may be considered as
a chemopreventive agent and its anticancer
properties should be further explored.20
Ethanolic extract of Hydrastis canadensis has been
tested for its possible anti-cancer potentials against
p-dimethylaminoazobenzene (p-DAB) induced
hepatocarcinogenesis in mice. A critical analysis of
results of this investigation shows anti-cancer
potentials of the drug suitable for use as a supportive
complementary medicine in liver cancer.21
The aqueous extract of Larrea divaricata has an
antiproliferative activity on T lymphoma (BW 5147)
cells in culture. Moreover the extract has in vivo
antitumor activity when it was administered to a
pregnant rat which had a spontaneous mammary
tumor. The effect of an extract of Larrea divaricata
was studied on a mammary carcinoma chemically
induced with N-nitrosomethylurea in females rats.
The extract was administered at a dose of 250 mg/kg
three times each week by two different routes,
subcutaneous (s.c.) and intratumoral (i.t.). the
investigation shows that the aqueous extract of this
plant has an in vivo antitumor activity with the
intratumor route being most effective in induction of
tumor regression.22
The cytotoxicity effect of tomato (Lycopersicum
esculentum) leaves (methanol extract ) on cancer
cells to address potential therapeutic in MCF-7
breast cancer cell lines and its toxicity towards Vero
cells was shown. The effect of extract towards
MCF-7 breast cancer cell lines and Vero cells were
observed using in vitro cytotoxicity assay to indicate
its active fractions and its half maximal inhibitory
concentration (IC50). Purified sample gave a
rational effect towards MCF-7 breast cancer cells
with IC50 value of 5.85 μg mL-.23
Ginseng (Panax ginseng), which is traditionally used
in some parts of the world as a popular remedy for
various diseases including cancer. It was
hypothesized that the ginsenoside Rp1, a component
of ginseng, reduces cancer cell proliferation through
inhibition of the insulin-like growth factor 1 receptor
(IGF-1R)/Akt pathway. Firstly, the efficacy of Rp1
was tested against human breast cancer cell lines.
Treatment with Rp1 inhibited breast cancer cell
proliferation and inhibited both anchorage-
dependent and -independent breast cancer cell
colony formation. In addition, to it the treatment
with 20 μM Rp1 induced cycle arrest and apoptosis-
mediated cell growth suppression. Findings further
indicated that Rp1 decreased the stability of the IGF-
1R protein in breast cancer cells. Therefore, it is
suggest that Rp1 has potential as an anticancer drug
and that IGF-1R is an important target for treatment
and prevention of breast cancer .24
Roots of Pfaffia paniculata have been well
documented for multifarious therapeutic values and
have also been used for cancer therapy in folk
medicine. Study has been performed in a human
breast tumor cell line, the MCF-7 cells. These are
the most commonly used model of estrogen-positive
breast cancer, and it has been originally established
in 1973 at the Michigan Cancer Foundation from a
pleural effusion taken from a woman with metastatic
breast cancer. Butanolic extract of the roots of P.
paniculata showed cytotoxic effect MCF-7 cell line,
as determined with crystal violet assay, cellular
death with acridine orange/ethidium bromide
staining, and cell proliferation with
immunocytochemistry of bromodeoxyuridine
(BrdU). Subcellular alterations were evaluated by
electron microscopy. Cells treated with butanolic
extract showed degeneration of cytoplasmic
components and profound morphological and
nuclear alterations. The results show that this
butanolic extract indeed presents cytotoxic
substances, and its fractions merit further
investigations.25
The plant Podophyllum peltatum produces
podophllyotoxin, a resin, throughout the entire plant
but especially in the rhizome. It is produced as a
form of protection from insects and other herbivores.
When ingested it causes gastroenteritis or even
death in humans. Edema (swelling) and eventual
deterioration of the spinal cord, brainstem,
cerebellum, and cerebral cortex have been reported
in rats treated with various amounts of the toxin.
Toxicities of other organs (although not specifically
mentioned) have been documented
Historically, this plant was widely used as a Chinese
herbal medicine because it is a wild Asian plant. It
was used to treat snakebites, general weakness,

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1147
poisons, condyloma accuminata, lymphadenopathy,
and certain tumors. It was also used by the
Penobscot Indians to treat cancer.26
Three anthraquinones, Cdc25B phosphatase
inhibitors, were isolated from the methanolic extract
of the roots of Polygonum multiflorum Thunb.
(Polygonaceae). Anthraquinones, physcion ,
emodin, and questin , inhibited the enzymatic
activity of Cdc25B phosphatase with IC50 values of
62.5, 30, and 34µgmL−1, respectively. Emodin and
questin strongly inhibited the growth of human
colon cancer cells, SW620 with GI50 values of 6.1
and 0.9µgmL−1, respectively. Commercially
available anthraquinones, chrysophanol, and rhein
also inhibited Cdc25B phosphatase with IC50 values
of 10.7 and 22.1µgmL−1, respectively.27
Three toxic proteins and one agglutinin were
purified from the seeds of Ricinus communis by
simple and fast method using Sepharose 4-B affinity
chromatography followed by Sephadex G-100 gel
filtration. The weakly adsorbed ricins A and B were
retarded and eluted with the buffer from the affinity
chromatographic column, while ricin C and ricinus
agglutinin had to be eluted with 0.1 M galactose.
The molecular weights of ricins A, B, and C were
about 62,000 and that of ricinus agglutinin was
120,000, estimated by amino acid compositions and
SDS gel electrophoresis. They all possessed two
non-identical subunits: A and B chains linked by one
disulfide bond. Their LD50 values were 4, 28, 14
and 112 micrograms per kg body weight of mice for
ricins A, B and C and ricinus agglutinin,
respectively. The amino acid compositions of the
three toxins and their A and B subunits were very
similar, but not identical, while ricinus agglutinin
showed a different composition. Ricin A is a newly
isolated lectin which has a strong inhibitory effect
on the growth of tumor cells. By using cell cultures,
it was demonstrated that the tumor cells were more
sensitive to lectin than non-transformed cells, and
that this could be caused by the higher binding
affinity of lectin to tumor cells than to non-
transformed cells.28
Barley and wheat: Lunasin, a unique 43 amino acid,
4.8 kDa cancer-chemopreventive peptide initially
reported in soybean and now found in barley and
wheat, has been shown to be cancer-
chemopreventive in mammalian cells and in a skin
cancer mouse model against oncogenes and
chemical carcinogens. To identify bioactive
components in traditional herbal medicines and in
search for new sources of lunasin, we report here the
properties of lunasin from Solanum nigrum L.
(SNL), a plant indigenous to northeast Asia. Lunasin
was screened in the crude extracts of five varieties of
the medicinal plants of Solanaceae origin and seven
other major herbal plants. An in vitro digestion
stability assay for measuring bioavailability was
carried out on SNL crude protein and autoclaved
SNL using pepsin and pancreatin. A nonradioactive
histone acetyltransferase (HAT) assay and HAT
activity colorimetric assay were used to measure the
inhibition of core histone acetylation. The inhibitory
effect of lunasin on the phosphorylation of
retinoblastoma protein (Rb) was determined by
immunoblotting against phospho-Rb. Lunasin
isolated from autoclaved SNL inhibited core histone
H3 and H4 acetylation, the activities of the HATs,
and the phosphorylation of the Rb protein. Lunasin
in the crude protein and in the autoclaved crude
protein was very stable to pepsin and pancreatin in
vitro digestion, while the synthetic pure lunasin was
digested at 2 min after the reaction. It was conclude
that lunasin is a bioactive and bioavailable
component in SNL and that consumption of SNL
may play an important role in cancer prevention.29
Solanum nigrum L. (SNL) has been traditionally
used as a herbal plant, whose fruit is believed to
have anti-tumor properties, although the mechanism
for the activity remains to be elucidated. An ethanol
extract from ripe fruits of SNL was prepared and
investigated the mechanism involved in its growth-
inhibitory effect on MCF-7 human breast cancer
cells. Results from proliferation assay using tritium
uptake showed that the proliferative capacity of
MCF-7 cells was strongly suppressed in the presence
of SNL ethanol extract. This was further confirmed
through MTT assay and trypan blue exclusion
experiments, which showed a very close correlation
between the SNL extract concentration and the
surviving cell numbers. The SNL extract-mediated
suppression of cell growth was verified to be
apoptotic, based on the appearance of DNA
laddering, increase in DNA fragmentation, and low
fluorescence intensity in nuclei after propidium
iodide staining of the cells. Furthermore, the SNL
extract was revealed to be a potential scavenger of
hydroxyl radicals and DPPH radicals rather than
superoxide anions. Collectively, findings suggest
that SNL fruit extract could be used as an anti-
oxidant and cancer chemo-preventive material.30
The DNA topoisomerase inhibitor β-lapachone is a
quinone obtained from the bark of the lapacho tree
(Tabebuia avellanedae) in South America. It has
been reported to possess a wide range of
pharmacological properties, and is a promising
cancer chemopreventive agent. The effects of β-
lapachone on the growth of the human hepatoma cell
line HepG2 were investigated. The results showed
that β-lapachone inhibits the viability of HepG2 by
inducing apoptosis, as evidenced by the formation of
apoptotic bodies and DNA fragmentation. Reverse

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1148
transcription-polymerase chain reaction and
immunoblotting results indicated that treatments of
cells with β-lapachone resulted in down-regulation
of anti-apoptotic Bcl-2 and Bcl-XL and up-regulation
of pro-apoptotic Bax expression. β-Lapachone-
induced apoptosis was associated with a proteolytic
activation of caspase-3 and -9 and degradation of
poly(ADP-ribose) polymerase protein. However, β-
lapachone treatment did not affect the inhibitor of
apoptosis proteins family and the Fas/FasL system.
Taken together, our study indicated that β-lapachone
may have potential as a chemopreventive agent for
liver cancer.31
The taxane diterpenoid from Taxol was first reported
in 1971, but it has only recently been recognized as a
highly effective anticancer drug. The history of
taxol's development is reviewed with an emphasis on
the problems that almost prevented the discovery of
its clinical activity, and on the key factors that kept it
under investigation. Recent research on the
structure-activity relationships and the synthesis of
taxol is also reviewed.32
In the determination the antioxidant and anti cancer
effects of Essiac, a tea prepared from a mixture of
four herbs Arctium lappa, Rumex acetosella, Ulmus
rubra and Rheum officinale, found that Essiac
inhibited hydroxyl radical-induced lipid
peroxidation by up to 50% at the 50% tea
preparation concentration. These data indicate that
Essiac tea possesses potent antioxidant and DNA-
protective activity, properties that are common to
natural anti-cancer agents. This study may help to
explain the mechanisms behind the reported anti-
cancer effects of Essiac.33
The activity of Uncaria tomentosa preparations on
cancer cells was studied using in vitro and in vivo
models. IC (50) values were calculated for
preparations with different quantitative and
qualitative oxindole alkaloid composition: B/W(37)
--bark extracted in water at 37 °C, B/W(b)--bark
extracted in boiling water, B/50E(37) --bark
extracted in 50% ethanol at 37 °C, B/E(b)--bark
extracted in boiling 96% ethanol, B/96E(37) --bark
extracted in 96% ethanol at 37 °C and B/SRT--bark
extracted in water and dichloromethane. Generally,
the results obtained showed a high correlation
between the total oxindole alkaloid content (from
0.43% to 50.40% d.m.) and the antiproliferative
activity of the preparations (IC(50) from >1000
μg/ml to 23.57 μg/ml). B/96E(37) and B/SRT were
the most cytotoxic preparations, whereas the lowest
toxicity was observed for B/W(37). B/96E(37) were
shown to be active against Lewis lung carcinoma
(LL/2) [IC(50) =25.06 μg/ml], cervical carcinoma
(KB) [IC(50) =35.69 μg/ml] and colon
adenocarcinoma (SW707) [IC(50) =49.06 μg/ml].
B/SRT was especially effective in inhibiting
proliferation of cervical carcinoma (KB) [IC(50)
=23.57 μg/ml], breast carcinoma (MCF-7) [IC(50)
=29.86 μg/ml] and lung carcinoma (A-549) [IC(50)
=40.03 μg/ml]. Further animal studies on mice
bearing Lewis lung carcinoma showed significant
inhibition of tumor growth by B/W(37) administered
for 21 days at daily doses of 5 and 0.5 mg
(p=0.0009). There were no significant changes in the
cell cycles of tumor cells with the exception of cell
decrease at the G2/M phase after the administration
of B/96E(37) at a daily dose of 0.5 mg and the
G(1)/G(0) cells cycle arrest demonstrated after the
B/SRT therapy at a daily-dose of 0.05 mg. All tested
preparations were non-toxic and well tolerated.34
Cycloviolacin O2 (CyO2), a cyclotide from Viola
odorata (Violaceae) has antitumor effects and
causes cell death by membrane permeabilization. In
the breast cancer line, MCF-7 and its drug resistant
subline MCF-7/ADR, the cytotoxic effects of CyO2
(0.2-10 microM) were monitored in the presence and
absence of doxorubicin (0.1-5 microM) using cell
proliferation assays to establish its chemosensitizing
abilities. SYTOX Green assays were Sperformed to
verify membrane permeabilization and showed
cellular disruption correlates with cyclotide
chemosensitization. Fluorescence microscopy
studies demonstrated increased cellular
internalization of doxorubicin in drug resistant cells
when coexposed to CyO2. Interestingly, CyO2 did
not produce significant membrane disruption in
primary human brain endothelial cells, which
suggested cyclotide specificity toward induced pore
formation in highly proliferating tumor cells.
Furthermore, three novel cyclotides (psyle A, C and
E) from Psychotria leptothyrsa (Rubiaceae) were
also monitored for cytotoxic activity. The cyclotides
displayed potent cytotoxicity (IC50 = 0.64->10
microM), and coexposure to cyclotides significantly
enhanced doxorubicin induced toxicity (IC50 =
0.39-0.76 microM). This study documents several
cyclotides with robust cytotoxicity that may be
promising chemosensitizing agents against drug
resistant breast cancer.35
Viscum album agglutinin-1 (VAA-1) from where it
is found is assumed to be the biologically most
active ingredient of mistletoe extracts that are often
used as adjuvant cancer therapy. To develop new
approaches for lung cancer treatment, the
antinewplastic activity of the evaluated the
antineoplastic activity of VAA-1 was evaluated in
combination with other chemotherapeutic drugs,
including doxorubicin, cisplatin and taxol in the
human lung carcinoma cell line A549.36
Detailed methods for in vitro/in vivo evaluation of
anticancer drugs, with special reference to mistletoe

Nidhi Agarwal et al /Int.J.PharmTech Res.2012,4(3)
1149
extracts from plant Viscum Album, have been
reviewed. Mistletoe extracts have been shown to
possess significant antitumor activity, in vivo,
against murine tumors, Lewis lung carcinoma, colon
adenocarcinoma 38 and C3H mammary
adenocarcinoma 16/C. Methods for the extraction of
biologically active alkaloids from mistletoe and their
anticancer activities are presented. The possible
origin of alkaloids in mistletoe plants, and their
contributions towards a mechanism of anticancer
activities of mistletoe extracts, were proposed.37
Proanthocyanidins (PAs), also known as condensed
tannins, are naturally occurring oligomers and
polymers of flavan-3-ol monomer units widely
found in the leaves, flowers, fruits, seeds, nuts and
barks of many plants. Grape seed (Vitis vinifera L.)
proanthocyanidins (GSPs) which have been used as
nutritional supplements and , as antioxidants, which
prevents in preventing atherosclerosis and
cardiovascular diseases. The anthracycline antibiotic
adriamycin (Doxorubicin, DXR) is a cancer
chemotherapeutic agent that interferes with the
topoisomerase II enzyme and generates free radicals.
In the present study, GSPs (1.680, 3.375, or 6.750
mg/mL) alone were examined for genotoxicity, and
combined with DXR (0.125 mg/mL) for
antigenotoxicity, using the standard (ST) and high
bioactivation (HB) versions of the wing somatic
mutation and recombination test in Drosophila
melanogaster. The results observed in both crosses
were rather similar. GSPs themselves did not show
genotoxicity at the doses used but they suppres the
DNA damage induced by DXR in a dose-dependent
manner. Comparison of the frequencies of wing
spots in the marker-heterozygous (MH) flies and
balancer-heterozygous (BH) flies from both crosses,
indicated that induced recombination was the major
response for the treatments with DXR alone. The co-
treatments demonstrated that GSPs have some anti-
mutagenic activity; however, anti-recombinagenic
activity was the major-response.38
Vitis Vinifera :- Investigations were carried out for
evalution of antitumor and antioxidant activity of
Ethanolic extract of vitis vinifera L.Leaves. For its
antitumor, antioxidant activity in Ehrlich ascites
carcinoma (EAC) induced swiss albino mice. The
antitumor effect and antioxidant role was assessed
using tumor volume, packed cell volume and
estimation of liver LPO and antioxidant enzymes
such as SOD, CAT. The Ethanolic extract
administered at 200 and 400 mg/kg b.w.per day for
14 days, after 24 hours of tumor inoculation.
Treatment with extract at a dose of 200 and 400
mg/kg increased mean survival time. Treatment with
extract also decreased the levels of LPO and
increased the levels of superoxide dismutase,
catalase. The results suggest that ethanolic extract of
vitis vinifera possess significant antitumor,
antioxidant effects in EAC tumor bearing mice.39
Zingiber officinale:- Ginger may act as an anti-
cancer and anti-inflammatory agent by inactivating
NFkappaB through the suppression of the pro-
inflammatory TNF-alpha.40
Some Anticancer Natural Products: 41
Name
Biological source
Geographical
source
Chemical
constituent
Uses
Aconite
Dried root of
aconitum napellus,
Ranunculacece
Hungary, germany,
spain Switzerland
Aconitine,
hypaconitine,
neopelline, napelline,
neoline
Treatment of
rheumatism,
inflammation.
Allium Sativum
(Garlic)
Bulb of the plant
know as allium
sativum, lilaceae
Central asia,
southern Europe,
USA and India
Carbohydrate,
protein (albumin),
fat, mucilage
Carminative,
aphrodisiac,
expectorant,
stimulant,
disinfectant
Artemisia
Unexpanded flower
heads of Artemisia
cina, Artemisia
buvifolia wall,
Artemisia maritime,
compositae
Pakistan, turkey,
from Kashmir to
kumaon in
Himalayas
Essential oil,
santonin, artemisin
Anthelmintic

Nidhi Agarwal et al /Int.J.PharmTech Res.2012,4(3)
1150
Name
Biological
source
Geographical
source
Chemical
constituent
Uses
Camellia
sinensis
Prepared leaves
and leaf buds of
Thea sinensis,
Theaceae
India, Shri
lanka., china,
Indonesia,
japan
Caffeine,
theobromine,
theophylline,
gallatonic acid
CNS stimulant, diuretic
Comptotheca
accuminata
Dried stem wood
of comptotheca
acuminate,
nyssaceae
China, Tibet,
southern china
Quinoline alkaloid,
camtothecin, 10
hydroxy
camptothecin, 10
methoxy
camptothecin
DNA topoisomerase
Iinhibitors, antitumour,
antileukemia
Catharanthus
roseus
Dried whole plant
of catharanthus
roseus,
apocunaceae
South africa,
india, USA,
Europe,
australia
Vincristine,
vinblastine,
ajmalicine
Antineoplastic, acute
leukemia, hodgkin’s
disease
Curcuma longa
Dried as well as
fresh rhizome of
the plant known
as curcuma
longa,
zingiberaceae
Tamil Nadu,
Andhra
Pradesh, kerala
Curcuminoids,
curcumin, volatile
oil, starch
Anti inflammatory, anti
arthritic, cervical
cancer
Glycyrrhiza
glabra
Dried peeled or
unpeeled root and
stolon of
glycyrrhiza
glabra,
leguminosae
Spain, sicily,
England
Glycurrhizin,
glycyrrhizinic acid
which on hydrolysis
yield glycyrrhetinic
acid
Expectorant,
demulcent, antigastric
effect
Panax ginseng
Dried root of
panax ginseng,
Araliaceae
Korea, china,
Russia, Canada,
USA
Ginsenoisides,
panaxosides,
chikusetsusaponin
Immunomodulatory
drugs
Podophyllum
peltatum
Dries rhizomes
and root of
podophyllum
peltatum,
barberidaceae
From Kashmir
to Sikkim and
parts of U.P
Podophyllin,
podophyllotoxin,
alpha and beta
peltatins
Cytotoxic action,
treatment of veneral,
purgative
Taxus
brevifolia
Dried leaves,
bark and root of
various species of
taxus, taxaceae
India, Canada,
America
Taxane,
cephalomannine, 10-
deacetyl baccatin,
taxol
Lung carcinoma,
gastric and cervical
cancers and also
carcinomas of head,
neck, prostate and
colon
Viola odorata
Dried aerial parts
obtained from
viola odorata,
violaceae
India (Kashmir,
himachal
Pradesh,
kumaon hills)
Essential oil,
alkaloid, saponins,
glycoside of methyl
salicylate.
Expectorant,
diaphoretic, antipyretic,
antibacterial
Zingiber
Rhizomes of
zingiber
officinale roscoe,
zingiberaceae
South asia,
Africa,
Australia,
Mauritius,
jamaica,
Taiwan, india.
Volatile oil, starch,
fat, fibre, inorganic
material, residual
moisture, acrid
resinous matter.
Stomachic, aromatic,
carminative, stimulant,
flavouring agent.

Nidhi Agarwal et al /Int.J.PharmTech Res.2012,4(3)
1151
Conclusion:
Medicinal plants have contributed a rich health to
human beings. Plant extracts and their bioactive
compounds present in them which are responsible
for anticancer activity have to be screened for their
valuable information. This review had given some of
the plants possessing anticancer activity for various
types of cancer. This review can help others to
explore herbs to further extent and its use in various
other disease and toxicity studies along with clinical
trials.
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