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Medicinal Plants Combating Against Cancer - a Green Anticancer Approach

Article  in  Asian Pacific journal of cancer prevention: APJCP · June 2014

DOI: 10.7314/APJCP.2014.15.11.4385 · Source: PubMed

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 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.11.4385
Medicinal Plants Combating Against Cancer - a Green Approach

REVIEW

Medicinal Plants Combating Against Cancer - a Green

Anticancer Approach
Sabira Sultana1*, Hafiz Muhammad Asif2, Hafiz Muhammad Irfan Nazar3,
Naveed Akhtar1, Jalil Ur Rehman1, Riaz Ur Rehman4

Abstract
Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities,
and morbidities around the world. It is the second leading cause of death all over the world. Although great
advancement have been made in the treatment of cancer progression, still significant deficiencies and room for
improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies,
such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects.
However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their
active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists
are required to find new lead anticancer constituent to fight disease. This review will help researchers in the
finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro
and in vivo.
Keywords: Anticancer activity - anticancer agents - cancer - medicinal plants

Asian Pac J Cancer Prev, 15 (11), 4385-4394

Introduction world is due to cancer. In the world wide, about 12.7

million cancers were diagnosed and 7.6 million deaths
Cancer is the life threatening and dreadful disease were reported in 2008 (Jemal et al., 2011). Cancer is the
characterized by the abnormal proliferation of cells that serious health issue of both developed and developing
invade the adjacent tissues and causes the destruction countries.
of these tissues (Gennari et al., 2007). Cancer spreads In 2012, there were an estimated 14.1 million cases
to distant organs through blood stream and lymphatic around the world, of these 7.4 million cases were in
vessels. Cancer results when disturbance occurs in two men and 6.4 million women. This number is expected to
types of genes i.e., oncogenes responsible for the growth increase to 24 million by 2035 (Ferlay, 2013).
of cancer cells, and tumor suppressor genes which Although cancer is considered to be more of a
prevent cancer from developing (Knudson et al., 2001). developed world issue, in fact rate of all cancers
It is often impossible to evaluate the specific cause for (excluding non-melanoma skin cancer) was 1.8 times
specific cancer. However there are certain factors known higher in more developed compared with less developed
to increase the risk of cancer such as tobacco use, alcohol, countries (Ferlay, 2013).
environmental pollutant, infectious agents, custom habits Chemotherapy as well as conventional treatment
and life styles (Lrigaray et al., 2007). Approximately 10% for the cure of cancer causes the adverse and toxic side
to 15% cancer is entirely hereditary (Anand et al., 2008). effects therefore fails to control the cancer disease. The
Cancers are named according to the type of cell the alternate solution for the harmful effects of synthetic
tumor resembles, for example carcinoma if they arise agents is the use of medicinal plants (Rashid et al., 2002).
from the epithelial cell lining, sarcoma if they arise from The plants have been used for the cure of cancer from a
mesodermal cell lining mean cancer of muscles, bones, prolonged period of time (Hartwell, 1982). The medicinal
cartilage and connective tissue, lymphoma if they arise plants contain chemical constituents of therapeutic value
from cells of immune system, leukemia if they arise from (Nostro et al., 2000). These chemical substances produce
cells of bone marrow. physiological action on the human body. It has been
More than six million deaths each year occur in the shown currently by clinical studies and phytochemical
University College of Conventional Medicine, Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur,
1

Department of Eastern Medicine & Surgery, Directorate of Medical Sciences, GCU, Faisalabad, Punjab, 2Department of Eastern
4

Medicine & Surgery, Faculty of Medical & Health Sciences, The University of Poonch, Rawalakot, AJ & K, 3University College of
Pharmacy, The University of Punjab, Lahore, Pakistan *For correspondence: drsabirachishti12@gmail

Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 4385

Sabira Sultana et al
Table 1. World Cancer Statistics for most Common compared to synthetic chemicals (Hamayun et al., 2006).
Cancers in 2012 Plants are the effective source of anticancer agent
Rank Cancer New case Percent of all and over 60% anticancer agents are derived from natural
diagnosed in cancer excluding resources including plants, marine organisms and
2012 (1000s) non melanoma microorganisms (Crag et al., 2005). Although number
of skin of anticancer agents are derived from medicinal plants
1 Lung 1,825 13 but still there’s present a number of plants that exhibits
2 Breast 1,677 11.9 anticancer potential but they have not yet been fully
3 Colorectum 1,361 9.7 investigated. The national cancer institute has screened
4 Prostate 1,112 7.9 around 114,000 extracts for anticancer activity (Shoeb et
5 Stomach 952 6.8 al., 2006). Therefore, there is a need to focus to evaluate
6 Liver 782 5.6 that whether these extracts will surely be the source
7 Bladder 430 3.1 of anticancer activity or whether these extracts can be
8 Non-hodgkin lymphoma 386 2.7 exploited to reach cancer blocking or remedial effects in
9 Leukaemia 352 2.5
human body.
10 Pancreas 338 2.4
11 Kidney 338 2.4
12 Brain 256 1.8 Anticancer Agents in Clinical Use
13 Melanoma of skin 232 1.6
14 Gall bladder 178 1.3 Vinblastine and vincristine are the bisindole alkaloids
15 Hodgkin Lymphoma 66 0.5 isolated from the Madagascar periwinkle, Catharanthus
roseus G. Don. (Apocynaceae) introduced a new era of
the use of plant material as anticancer agents. They were
Table 2. The Number of Cases in More Developed and the first plant derived agents to advance into clinical
Less Developed Countries as of the Year 2012 use for the treatment of cancer (Cragg and Newman,
Age standardized Rate per 100,000 (world) 2005). Vinblastine and vincristine are primarily used in
Cancer World More Less combination with other cancer chemotherapeutic drugs
developed developed for the treatment of different types of cancers, including
All cancer excluding non-melanoma skin cancer leukemias, lymphomas, testicular cancer, breast and lung
182.3 268.3 147.7 cancers, and Kaposi’s sarcoma (Cragg and Newman,
Lung 23.1 30.8 20 2005).
Colorectum 17.2 29.2 11.2 Camptothecin, isolated from the wood bark and fruits
Stomach 12.1 10.6 12.7 of Chinese ornamental tree Camptotheca acuminate Decne
Melanoma of skin 3 9.6 0.8 (Nyssaceae), was advanced to clinical trials by NCI in the
Bladder 5.3 9.5 3.3
1970s but its use was halted because of severe bladder
Kidney 4.4 9.2 2.6
Non-hodgkin lymphoma 5 8.6 3.6 toxicity (Potmeisel, 1995). Topotecan and irinotecan are
Leukaemia 4.7 7.2 3.8 semi-synthetic derivatives of camptothecin and are active
Pancrease 4.2 7.2 2.8 against ovarian and small cell lung cancers, and colorectal
Liver 10.1 5.4 12 cancers, respectively (Creemers et al., 1996; Bertino,
Brain 3.4 5.1 3 1997).
Gall bladder 2.2 2.1 2.2 Homoharringtonine is cephalotaxus alkaloid isolated
Hodgkin lymphoma 0.9 2.1 0.6 from the Chinese tree Cephalotaxus harringtonia
var. drupacea (Sieb and Zucc.) (Cephalotaxaceae), is
another plant-derived agent in clinical use (Powell et
investigation that many herbs exhibit anti tumor potential
al., 1970; Itokawa et al., 2005). A racemic mixture of
against various cancers (Sharma et al., 2011).
harringtonine and homoharringtonine are active against
Medicinal plants provide outstanding contribution to
acute myelogenous leukemia and chronic myelogenous
modern therapeutics; approximately 100 plants based new
leukemia (Kantarjian et al., 1996; Cragg and Newman,
drugs were introduced in the USA drug market during
2005).
1950 to 1970 including reserpine, deserpidine, vinblastine,
Ellipticine is an antitumor alkaloid isolated from a
vincristine. All these derived from higher plants. From
Fijian medicinal plant Bleekeria vitensis A.C. Sm, is
1971 to 1990 new plant based drugs came into being
marketed in France for the treatment of breast cancer
all over the world such as ectoposide, eguggulsterone,
(Cragg and Newman, 2005).
artemisinin and ginkgolides. During 1991 to 1995 2%
Paclitaxel (Taxol®) derived from the bark of the
drugs were introduced including pacitaxel, topotecan,
Pacific Yew, Taxus brevifolia Nutt. (Taxaceae), is another
gomishin, irinotecan etc. (Pandey et al., 2011). However
success in natural product drug discovery. Several Native
in the middle of 20th century, the use of medicinal plants
American Tribes use various parts of Taxus brevifolia and
was reduced one fourth as researchers favor the use of
other Taxus species (e.g., Taxus Canadensis Marshall,
synthetic chemicals for curing diseases. Now the trend is
Taxus baccata L.) for the treatment of some non-cancerous
going to be changed and the people favor the medicinal
cases (Cragg and Newman, 2005) while Taxus baccata
plants as they contain natural products that are effective,
was reported to use in the Indian Ayurvedic medicine for
chemically balanced and have fewer side effects as
the treatment of cancer. Paclitaxel is used against ovarian
4386 Asian Pacific Journal of Cancer Prevention, Vol 15, 2014
 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.11.4385
Medicinal Plants Combating Against Cancer - a Green Approach
cancer, advanced breast cancer, small and non-small cell acronycine, and normelicopidine isolated from Acronychia
lung cancer (Rowinsky et al., 1992). Baueri Schott (Bauerella australiana Borzi) bark shown
Podophyllotoxin is an important anticancer liganan, to have antitumor activity. Among three alkaloids,
which was isolated as the active anti-tumor agent from experimental evidence showed acronycine has the
the roots of Podophyllum species, Podophyllum peltatum broadest antitumor spectrum. It is chemically unrelated
Linnaeus and Podophyllum emodi Wallich (Berberidaceae) to any of the presently utilized antitumor agents therefore
(Stahelin, 1973). Etoposide and teniposide are two most represents a new lead in the search for agents effective in
successful anticancer derivatives of epipodophyllotoxin the chemotherapeutic management of human neoplasms
and are used in the treatment of lymphomas and bronchial (Svododa et al., 1996).
and testicular cancers (Cragg and Newman, 2005; Harvey,
1997). Rosa roxburghii tratt
Rosa roxburghii Tratt and Fagopyrum cymosum are
Anticancer Activity Of Medicinal Plants two examples of plants which have beneficial effects in
improving immune responses, enhancing digestive ability
Allium sativum and demonstrating anti-aging effects. Some evidence
Allium sativum L. garlic is among the oldest of all shows that herbal medicine soups containing extracts of
cultivated plants being used as a food, having a unique taste these two medicinal plants i.e Rosa roxburghii Tratt and
and odor along with some medicinal qualities. Modern Fagopyrum cymosum have efficacy in treating malignant
scientific research has revealed that the wide variety of tumors. The study was therefore undertaken to evaluate
dietary and medicinal functions of garlic can be because anticancer effects against three carcinoma cell lines
of the sulfur compounds present in it. The compound (human esophageal squamous carcinoma CaEs-17, human
allicin, methyl allyl trisulfide, and diallyl trisulfide have gastric carcinoma SGC-7901 and pulmonary carcinoma
antibacterial, antithrombotic, and anticancer activities A549) by MTT assay and flow cytometry. IC30 of Rosa
respectively (Ariga et al., 2006). It is a remarkable plant, roxburghii Tratt and Fagopyrum cymosum were obtained
which has multiple beneficial health effects such as by MTT assay. Combination of Rosa roxburghii Tratt
hypolipidemic, antiarthritic, antimicrobial, antithrombotic, and Fagopyrum cymosum showed significant inhibition
hypoglycemic and antitumor activities. Different garlic of cell growth and increase in apoptosis; the mRNA and
preparations including fresh garlic extract, aged garlic, protein expression levels of Ki-67 and Bcl-2 in Rosa
garlic oil and a number of organo sulfur compounds roxburghii Tratt and Fagopyrum cymosum group were
derived from garlic shown to have chemopreventive all greatly decreased, while the expression of Bax was
activity. The chemopreventive activity has been attributed markedly increased. These results therefore show that
to the presence of organo sulfur compounds in garlic. The the synergistic antitumor effects of combination of Rosa
two major compounds in aged garlic, S-allylcysteine and roxburghii Tratt and Fagopyrum cymosum are related to
S-allylmercapto-L-cysteine possess the highest radical inhibition of proliferation and induction of apoptosis (Liu
scavenging activity. In addition, S-allylcysteine has been et al., 2012).
found to reduce the growth of chemically induced and
transplantable tumors in animal models. Therefore, the Artemisia capillaries
use of garlic may provide some kind of protection from Artemisia capillaries is a major food and medicinal
cancer development (Thomson et al., 2003). resource plan found in Korea. The methanol extracts of
Artemisia capillaries were used for the evaluation of
Annona muricata L DPPH(2,2-diphenyl- 1-picrylhydrazyl) scavenging, total
George et al. (2012) evaluated the cytotoxic potential phenolic content, total flavonoid content, hydroxyl radical
of n-butanolic leaf extract of Annona muricata L. on (OH) scavenging, reducing power assay as antioxidant
WRL-68 (normal human hepatic cells), MDA-MB-435S activity, as well as anticancer activities using MTT assay.
(human breast carcinoma cells) and HaCaT (human As a result, the Artemisia capillaries extracts exhibited
immortalized keratinocyte cells) lines by XTT assay. The potential antioxidant activity and anticancer activity in
result revealed that the extract at its lower doses exhibited vitro. These results suggest that the Artemisia capillaries
a significant cytotoxicity on MDA-MB-435S and HaCaT extracts have a potential alleviated oxidation process, cell
cells with the IC50 values of 29.2 and 30.1 µg respectively, motility activity, and tumorigenesis (Jung et al., 2008).
while it exhibited only a moderate cytotoxicity towards
WRL-68 with a comparatively higher IC50 value of 52.4 Derris scandens
µg, clearly indicating differential cytotoxicity, at least at The ethanolic extract of the medicinal plant,
the lower doses tested. On the other hand, the cytotoxic Derris scandens Benth has been identified as a potent
effect of the extract was similar on both normal and radiosensitizer of human colon cancer HT29 cells.
cancer cell lines, at the highest tested dose. This study Cell death mechanisms underlying radiosensitization
therefore confirms the presence of therapeutically active activity of D. scandens extract was further identified.
antineoplastic compounds in the n-butanolic leaf extract The study showed that treatment of HT-29 cells with D.
of Annona muricata (George et al., 2012). scandens extract in combination with gamma irradiation
synergistically sensitizes HT-29 cells to cell lethality
Acronychia bauer by apoptosis and mitotic catastrophe. Moreover, the
Triterpene lupeol and the alkaloids melicopine, extract was found to decrease Erk1/2 activation. This
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 4387
Sabira Sultana et al
study concludes that D. scandens extract mediates dependent manner. Apoptosis was induced by Atractylis
radiosensitization via at least two distinct modes of cell lancea via arresting the cells in the G1 phase. Moreover,
death and silences pro-survival signaling in HT-29 cells Atractylis lancea effectively reduced telomerase activity
(Arunee et al., 2014). through inhibition of mRNA and protein expression. The
study therefore, demonstrated that Atractylis lancea exerts
Goniothalamus macrophyllus anti-proliferative effects in Hep-G2 cells (Wei et al., 2013).
Goniothalamus is a medicinal plant belonging to the
Annonacae family; contains substances which possess Phyllanthus emblica
anticancer properties towards several tumor cell lines. Phyllanthus emblica is known to exhibit various
Goniothalamin, a natural compound extracted from pharmacological properties. Antimetastatic potential
Goniothalamus sp. Apoptosis induction by goniothalamin of a Phyllanthus emblica aqueous extract was
in the Hela cervical cancer cell line was observed by evaluated. Cytotoxicity to human fibrosarcoma cells,
MTT assay method. The IC50 value of goniothalamin HT1080, was assessed by viability assay using the
was 3.2±0.72 µg/ml. It was concluded that morphological 3-(4,5-dimethylthiazol,2-yl)-2,5-diphenyltetrazolium
changes and biochemical processes associated with bromide (MTT) reagent. Cell migration, cell attachment
apoptosis were evident on phase contrast microscopy onto normal surfaces of cell culture plates, the molecular
and fluorescence microscopy. DNA damage, DNA mechanism of antimetastatic activity were investigated
fragmentation, caspase-9 activation and a large increase in using chemotaxis chambers containing membranes pre-
the sub-G1 and S cell cycle phases confirm the happening coated with collagen IV, measuring the gene expression
of apoptosis in a time-dependent manner. The study of matrix metalloproteinases, MMP2, and MMP9, using
there showed that goniothalamin possesses a promising reverse transcription-polymerase chain reaction (RT-PCR)
cytotoxicity effect against cervical cancer cells (Hela) assay respectively. The result of the study showed that
and the cell death mode induced by goniothalamin was Phyllanthus emblica extract reduces cell proliferation,
apoptosis (Aied et al., 2013). migration, invasion, and adhesion in both dose- and time-
dependent manners, especially growth arrest with low
Angelica sinensis IC50 value (Waraporn et al., 2013).
Angelica sinensis polysaccharide, a major active
component in Dong quai (Chinese Angelica sinensis), Astragalus membranaceus
effectively inhibited human acute myelogenous leukemia Astragalus membranaceus, a commonly used Chinese
CD34+CD38 cell proliferation in vitro culture in a medicinal plant, has been shown to restore the impaired
dose-dependent manner. Moreover, Angelica sinensis T cell functions in cancer patients. The in vitro and in
polysaccharide exerted cytotoxic affects on acute vivo anti-tumor effects of root of A. membranaceus were
myelogenous leukemia K562 cells, especially LSC- investigated. Five bioactive fractions were isolated, the
enriched CD34+CD38 cells. Colony formation assays fraction designated as AI was found to be the most active
further showed that acute myelogenous leukemia among the five fractions with respect to its mitogenicity on
significantly suppressed the formation of colonies derived murine splenocytes. Its cytostatic activities, macrophage
from acute myelogenous leukemia CD34+CD38 cells function, tumor necrosis factor production, induction
but not those from normal CD34+CD38 cells. Angelica of lymphokine-activated killer cell and tumor cell
sinensis polysaccharide induced CD34+CD38− cell differentiation were examined. Cytostatic activity of
senescence, which was strongly related with a series of AI against the macrophage-like tumors and the myeloid
characteristic events, including up-regulation of p53, tumors were found to be more sensitive, whereas the
p16, p21, and Rb genes and changes of related cell fibroblast-like tumors and the mouse Ehrlich ascites
cycle regulation proteins P16, P21, cyclin E and CDK4, tumor appeared to be relatively resistant. Moreover, AI
telomere end attrition as well as repression of telomerase could effectively suppress the in vivo growth of syngeneic
activity. On the basis of these findings, it was concluded tumor in mice. Collectively, the results showed that A.
that Angelica sinensis polysaccharide represents a membranaceus could exhibit both in vitro and in vivo
potentially important agent for leukemia stem cell-targeted anti-tumor effects, which might be due to the anti-tumor
therapy (Jun et al., 2013). immune mechanism of the host (William et al., 2007).

Atractylis lancea (Thunb.) DC. an important medicinal Beta vulgaris

herb in Asia, has been shown to have anti-tumor effects In vitro inhibitory effect of Beta vulgaris (beet)
on cancer cells. The potential effects and molecular root extract on Epstein-Barr virus early antigen (EBV-
mechanisms of Atractylis lancea was evaluated in vitro EA) was evaluated. The result showed high order of
on the proliferation of the Hep-G2 liver cancer cell line. activity compared to capsanthin, cranberry, red onion
Cell viability was determined by MTT test in Hep-G2 cells skin and short and long red bell peppers. An in vivo
incubated with an ethanol extract of Atractylis lancea. anti-tumor activity evaluated against the mice skin and
Then, the effects of Atractylis lancea on apoptosis and cell lung bioassays. Result also revealed a significant tumor
cycle progression were investigated by flow cytometry. inhibitory effect. The combined findings suggest that Beta
Results show that Atractylis lancea effectively inhibits vulgaris (beetroot) ingestion can be one of the useful
proliferation in Hep-G2 cells in a concentration- and time- means to prevent cancer (Kapadia et al., 1996).

4388 Asian Pacific Journal of Cancer Prevention, Vol 15, 2014

 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.11.4385
Medicinal Plants Combating Against Cancer - a Green Approach
Camellia sinensis shows significant cytotoxic effects on the Hella cell line
Green tea is an aqueous infusion of dried unfermented and little effect on Vero cell line (Patel et al., 2009). This
leaves of Camellia sinensis (Family Theaceae) possesses shows that Solanum nigrum may indeed have potential
numerous biological activities including antimutagenic, as an anticancer herb.
antibacterial, hypocholesterolemic, antioxidant, antitumor
and cancer preventive activities. It has been reported that Woodfordia fruticosa
green tea leaves contains six compounds (+)-gallocatechin The in vitro cytotoxic activity of the 95% ethanol
(GC), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), extract, 50% ethanol extract and hot water extract of
(-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate woodfordia fruticosa at 100ug/100ml was evaluated
(EGCG) and caffeine. These compounds were tested by SRB assay against six human cancer cell lines viz
against four human tumor cells lines such as (MCF-7 ., lung cancer cells (A-459, NCI-H23), colon cancer
breast carcinoma, HT-29 colon carcinoma, A-427 lung cells (COLO-205, SW-620), Liver cancer cells (HEP-
carcinoma and UACC-375 melanoma). EGCG, GC and 2) and Neuroblastoma cancer cells (SK-N-MC). It was
EGC found to be most potent against all four tumor cell demonstrated by the result that the 95% ethanol extract
lines. In view of these extensive in vitro studies, it would from the flowers of plants showed cytotoxicity against
be of considerable interest to evaluate all three of these two cancer cell lines viz., HEP-2 and SK-N-MC and did
components in animal tumor model systems before final not give any significant activity against other four human
decisions are made concerning which of these potential cancer cell lines. While the other two extract 50% ethanol
chemopreventive agent should be taken into broad clinical and hot water extract did not give any cytotoxic activity
trials (Valcis et al., 1996). against human cancer cell lines (Sharma et al., 2011).
The study shows that Woodfordia fruticosa possess the
Camptotheca acuminate cytotoxic potential.
Camptothecin (CPT) is an anticancer and antiviral
alkaloid isolated from Chinese tree Camptotheca Glochidion zeylanicum
acuminata (Nyssaceae). Several attempts have been The plant Glochidion zeylanicum (Euphorbiaceae)
made to produce CPT from cell suspensions. The hairy commonly named as Neeru in traditional system of
roots of Camptotheca acuminata produce and secrete medicine plays an important role in curing many diseases
Camptothecin as well as the more potent and less toxic like cancer, stomachic, diabetes, refrigerant. The previous
natural derivative, 10- hydroxycamptothecin, into the studies have shown that potential anti-tumor activity of
medium (Lorence, 2004). lupane type triterpinoids from stem bark of Glochidion
zeylanicum, and Glochidionisides A-D, Megastigmane
Boerhaavia diffusa glycosides from the leaves of Glochidion zeylanicum.
Boerhaavia diffusa (Linn.) (Syn. B. repens L.; B. The in vitro cytotoxic activity of the methanol extract
procumbens Roxb) commonly known as “Punarnava” of the roots of Glochidion zeylanicum was evaluated
in indian system of medicine is a perennial creeping against human cancer cell lines Hep G2, HT-29 and PC-
herb belong to family Nyctaginaceae. Its ethanol extract 3. The study shows that the methanol extract of root of
showed cytotoxic effect against Hela cell lines and inhibit Golichidion zeylanicum possess cytotoxic potential in
the S-phase of the cell cycle. It also inhibits the growth of a concentration dependent manner and give significant
cancer cells in DMBA- induced cancer carcinogenesis in cytotoxic activity on PC-3 cell lines (Sharma et al,2011).
mice through free radical scavenging mechanism (Bharali However, further study may still be necessary to evaluate
et al., 2003). the chemical nature and the active principle of the root
which is responsible for its activity.
Solanum nigrum
Solanum nigrum Linn. belongs to family Solanaceae Acanthus ilicifolius
commonly known as black nightshade, Makoy and deadly In vivo anticancer activity of the whole plant of
night shade. It possesses no. of medicinal properties Acanthus ilicifolius was evaluated using different extract
like antimicrobial, anti-oxidant, cytotoxic properties, and fractioned by comet assay against Hela and KB cell
antiulcerogenic, and hepatoprotective activity. Solanum lines. The extracts were fractioned with ethyl acetate,
nigrum is a potential herbal alternative as anti-cancer agent acetone and water. The data demonstrated that ethylacetate
and its one of the active principle Diosgenin reported to extract of the whole plant of Acanthus ilicifolius has a
be responsible for this action. potential cytotoxic activity on Hela cell and KB cell lines
A Hela cell is an immortal cell line used in medical (Kajure et al., 2011).
research. The cell line was derived from cervical cancer
cells of Henrietta Lacks, who died from her cancer in Cucurbita maxima
1951. At first, the cell line was said to be named after a In vivo methanol extract of the aerial part of Cucurbita
“Helen Lane” in order to preserve Lacks’s anonymity. maxima was studied for anticancer activity against Ehrlich
Anticancer activity of Solanum nigrum was evaluated. The ascities carcinoma cells in mice. Oral administration of
methanol extract of the fruit of Solanum nigrum was tested the methanol extract of the Cucurbita maxima at a dose of
for its inhibitory effects on the Hella cell line and vero 200mg/kg and 400mg/kg give the cytotoxicity against the
cell line by SRB assay and MTT assay in concentration Ehrlich ascities carcinoma cells in mice in dose dependent
range between 10mg/ml to 0.0196mg/ml. Both the assay manner (Saha et al., 2011).
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 4389
Sabira Sultana et al
Parthenium hysterophorus possible protective effects of Amaranthus paniculatus
The methanol and acetone extract of the flowers leaves on the antioxidant defense system in Ehrlich’s
of Parthenium hysterphorus were studied for in ascites carcinoma (EAC) -treated mice. The results of
vitro anticancer activity against the A-549 (Lung this study demonstrated the indirect inhibitory effect
adenocarcinoma) cell lines by MTT assay and Tryphan of the extract in EAC bearing group, which is probably
blue exclusion assay. In this study result shows that mediated by the enhancement and deactivation of either
acetone extract of Parthenium hysterphorus give greater macrophages or cytokine production. In addition, the
anticancer activity compare to methanol extract (Kumar result of the study had shown the anticancer effect of the
et al., 2011). ethanolic extract of Amaranthus paniculatus against EAC
in swiss albino mice. Moreover a significant enhancement
Inonotus obliquus of mean survival time and decrease in tumor volume
The Chaga mushroom (Inonotus obliquus) has been suggest the delaying impact of Amaranthus paniculatus
used traditionally as a medicine to treat cancers. It is in cell division. Cytological studies of Leishman-stained
hypothesized that the pure compounds (3β-hydroxy- tumor cell smear also have revealed a decrease in the
lanosta-8, 24-dien-21-al, inotodiol and lanosterol, number of mitotic cells following Amaranthus paniculatus
respectively) isolated from I. obliquus would inhibit invivo extract treatment when compared with that of EAC control
tumor growth in Balbc mice bearing Sarcoma-180 cells (S- (Sreelatha et al., 2012).
180) and growth of human carcinoma cells in vitro. To test
this hypothesis, the growth inhibition of each subfraction Curcuma longa
isolated from I. obliquus were tested in vitro against human Anticancer potential of the rhizomes of turmeric
carcinoma cell lines (lung carcinoma A-549 cells, stomach (Curcuma longa) was evaluated in vitro using tissue
adenocarcinoma AGS cells, breast adenocarcinoma MCF- culture methods and in vivo in mice using Dalton’s
7 cells, and cervical adenocarcinoma HeLa cells). The lymphoma cells grown as ascites form. C. longa extract
study showed that all of the subfractions isolated from I. inhibited the cell growth in Chinese Hamster Ovary (CHO)
obliquus possessess significant cytotoxic activity against cells at a concentration of 0.4 mg/ml and was cytotoxic
the selected cancer cell lines. However in vivo results to lymphocytes and Dalton’s lymphoma cells at the same
showed subfraction 1 at concentrations of 0.1 and 0.2 concentration. Cytotoxic effect was happened within 30
mg/mouse per day significantly decreased tumor volume min at room temperature (30oC). Curcumin was found
by 23.96% and 33.71%, respectively, as compared with to be the active constituents of C. longa which showed
the control. Subfractions 2 and 3 also significantly slow cytotoxicity to lymphocytes and Dalton’s lymphoma
down tumor growth in mice as compared with the control cells at a concentration of 4 mg/ml. Initial experiments
mouse tumor. The overall result of the study showed that indicated that C. longa extract and curcumin reduced the
Subfraction 1 from I. obliquus exhibited greater inhibition growth of animal tumours (Kuttan et al., 1985).
of tumor growth than subfractions 2 and 3, which agrees Cynara syriaca and Cynara cardunculus: Apoptotic
well with the in vitro results. The results suggest that I. and cytotoxic activity of plant extracts obtaining from
obliquus could be used as natural anticancer ingredients Cynara syriaca in and Cynara cardunculus (artichoke
in the food and/or pharmaceutical industry (Mijachung et species) against DLD1 colorectal cancer cells was
al., 2010). determined. This paper was the first report, concerning
with, positive effects of plant extracts obtained from two
Citrus maxima different artichoke species against to colorectal cancer cell
The methanol extract of the leaves of the Citrus line. In this study, their results demonstrated that artichoke
maxima was evaluated for its anticancer activity at a dose extracts had inhibitory effects on the proliferation of
of 200-400mg/kg against Ehrlich Ascities carcinoma cell human colorectal cancer DLD1 cells. Extracts not only
lines in Swiss albino mice. Oral administration of the hold back cell proliferation but also induce apoptotic
methanol extract of the leaves of Citrus maxima reverses pathway on DLD1 cells (Simsek et al., 2013).
the tumor parameters such as tumor volume, viable tumor
cell count, and increase body weight, hematological Withania somnifera
parameters and life span. Therefore study show that Withania somnifera (L.) family (Solanaceae) Dunal
methanol extract of the aerial part of Citrus maxima (also known as ashwagandha), is a medicinal plant
possess antitumor activity in a dose dependent manner having antitumor, anti-aging, anti-stess, anti-oxidant
(Kundusen et al., 2011). and immunomodulatory properties. In vitro cytotoxicity
of the ethanol extracts of root, stem and leaves of
Amaranthus paniculatus Withania somnifera was evaluated against five human
Amaranthus paniculatus (Amaranthaceae) is cancer cell lines of four different tissues i.e, Pc-3,
commonly known as “Rajgira” in India and “Amaranth” in DU-145(Prostrate), HCT- 15(colon), A-549(Lung) and
English. This plant is cultivated by Native Americans for IMR-32(Neuroblastoma).50% ethanol extract showed
several thousand years and now cultivated worldwide. It is the significant anticancer activity of different parts of
the world’s most nutritious plant and used traditionally for Withania somnifera. But the 50% ethanol extract of the
respiratory infections, vision defects, tuberculosis, fleshy leaves of Withania somnifera give the maximum activity
tumors, liver complaints and inflammations. Sreelatha et against the cell lines compare to other two parts i.e, root
al. (2012) investigate the antioxidant capacity and the and stem (Yadav etal., 2010).
4390 Asian Pacific Journal of Cancer Prevention, Vol 15, 2014
 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.11.4385
Medicinal Plants Combating Against Cancer - a Green Approach
Melissa officinalis ulcers. Research revealed that plant contains pentacyclic
Melissa officinalis L. commonly known as lemon balm triterpenoids such as lupeol, betulin, betulinaldehyde,
is one of the most used medicinal plants in Europe and betulinicacid, beta-sitosterol and Iridoid glucosides having
the Mediterranean region, as a herbal tea for its aromatic, c-11 carboxylic acid group were also present and other
digestive and antispasmodic properties in nervous compounds present are flavanoids, alkaloid, steroids,
disturbance of sleep and functional gastrointestinal tannins, wax esters are the most considerable compounds.
disorders. Saraydin. et al (2012) investigated the The in vivo cytotoxic activity of the methanol extract
antiproliferative properties of Melissa officinalis from of the leaf of Avicennia officinalis was studied against
Turkey on breast cancer. Melissa officinalis showed Ehrlich Ascties Carcinoma cell lines in Rodents. Result
cytotoxicity against three cancer cell lines, inducing demonstrated that the oral administration of the methanol
increase in Annexin-positive cells. Furthermore, study extract of the leaf of Avicennia officinalis at a dose of
showed that mean tumor volume inhibition ratio in 200mg/kg and 400mg/kg give the anticancer activity
Melissa officinalis treated group was 40% compared and reverse the hematological changes induced by cell
with the untreated rats. This study confirmed that Melissa lines. Therefore result show the cytotoxic potential in the
officinalis extracts have antitumoral potential against methanol extract of the leaves of Avicennia officinalis in
breast cancer (Saraydin et al., 2012). dose dependent manner (Sumithra et al., 2011)

Curcuma zedoaria Glycyrrhiza glabra

Curcuma zedoaria belonging to the family Licochalcone (LA) is a novel estrogenic flavonoid
Zingiberaceae has been used in the traditional system of isolated from Glycyrrhiza Glabra showed significant
medicine in treating many human ailments and is found antitumor activity in various malignant human cell lines.
to possess many biological activities. Isocurcumenol Evaluation of its anti-cancer activities were carried out
was characterized as the active compound of C. zedoaria in LA-elicited growth control and induction of apoptosis
and was found to inhibit the proliferation of cancer cells using androgen- independent p53-null PC-3 prostate cancer
without inducing significant toxicity to the normal cells. In cells. Licochalcone induced modest level of apoptosis but
vivo tumour reduction studies of C. zedoaria revealed that had more pronounced effect on cell cycle progression
a dose of 35.7mg/kg body weight significantly reduced the arresting cells in G2/M, accompanied by suppression
ascitic tumour in DLA-challenged mice and increased the of cyclin B1 and cdc2. It also inhibited phosphorylation
lifespan with respect to untreated control mice (Lakshmi of Rb, decreased expression of transcription factor E2F
et al., 2011). concurrent with reduction of cyclin D1, down-regulation
of CDKs 4 and 6, but increased cyclin E expression. These
Daucus carota findings provide mechanistic explanation for Licochalcone
Three constituents, epilaserine, β-sitosterol and activity and suggest that it possess chemopreventive
laserine were obtained from the lipophilic fraction of potential and its anticancer effect should be further
Daucus carota. Among the 3 constituents, epilaserine explored (Yue fu et al., 2009).
showed significantly inhibitory activity against leukemia
cell, HL-60 (Jing et al., 2008). Nigella sativa
Anticancer activity of the methanol extract of the
Rubia cordifolia seeds of Nigella sativa was evaluated by MTT assay on
Rubia cordifolia Linn, which belongs to the Rubiaceae different cancer and normal cell lines such as HL-60,
family, is a well-known herb used in Ayurvedic medicine. U-973 AND HEK 293T. It was demonstrated by the result
Shilpa. et al (2012) investigated the influence of a that methanol extract of the Nigella sativa seeds possess
methanolic extract of Rubia cordifolia on the induction potent inhibitory activity against Hl-60 and U-937 cell
of apoptosis in HEp-2 (human laryngeal carcinoma) lines (Raval et al., 2010).
cell line. Rubia cordifolia extract decrease the viability
of HEp-2 cell lines in a dose- dependent manner and Hydrastis canadensis
induced apoptosis. Antiproliferative effect was confirmed Ethanolic extract of Hydrastis canadensis has
by, cell viability quantified by MTT assay. A dose and been evaluated for its anti-cancer potentials against
time dependent fall in mitochondrial activity was noted p-dimethylaminoazobenzene (p-DAB) induced
in HEp-2 cell line showing IC50 at 10mg/ml. Further hepatocarcinogenesis in mice. Analysis of results of this
studies are needed to confirm this effect as the present study shows anti-cancer potentials of the drug and suitable
work opens new perspectives for cancer treatment based for use as a supportive complementary medicine in liver
on ethnopharmacological studies (Shilpa et al., 2012). cancer (Karmakar et al., 2010).

Avicennia officinalis Larrea divaricata

Avicennia officinalis is an ever green tree found The aqueous extract of Larrea divaricata has an
infrequently on the banks of river and rarely found near antiproliferative activity on T lymphoma (BW 5147)
the sea. Fruits are used to treat boils and tumours. Poultice cells in culture. Moreover the effect of an extract of
of unripe seed stop inflammation, roots used for its Larrea divaricata was studied on a mammary carcinoma
aphrodisiac, bark is used to treat skin especially scabies, chemically induced with N-nitrosomethylurea in female
resins for snake bite and contraceptive by women, seed for rats. The extract was administered at a dose of 250
Asian Pacific Journal of Cancer Prevention, Vol 15, 2014 4391
Sabira Sultana et al
mg/kg three times each week by two different routes, to higher binding affinity of lectin to tumor cells than to
subcutaneous (s.c.) and intratumoral (i.t.). The result non- transformed cells (Lin et al., 1986).
showed that the aqueous extract of this plant possess an
in vivo antitumor activity with the intratumor route being Barley and wheat
most effective in tumor regression (Anesini et al., 2011). A unique 43 amino acid, Lunasin, 4.8 kDa isolated
from barley and wheat is a cancer-chemopreventive
Lycopersicum esculentum peptide. It has been shown to be cancer- chemopreventive
The cytotoxicity effect of methanol extract of leaves in mammalian cells and in a skin cancer mouse model
of tomato (Lycopersicum esculentum) was evaluated on against oncogenes and chemical carcinogens (Jeong et
cancer cells (MCF-7 breast cancer cell lines and Vero al., 2007).
cells using in vitro cytotoxicity assay to indicate its active
fractions and its half maximal inhibitory concentration Tabebuia avellanedae
(IC50). Purified sample gave a potential effect towards The DNA topoisomerase inhibitor β-lapachone is
MCF-7 breast cancer cells with IC50 value of 5.85 μg a quinone isolated from the bark of the lapacho tree
mL- (Chick et al., 2010) (Tabebuia avellanedae) in South America. It has been
reported to possess a numerous of biological activities,
Panax ginseng and is a promising cancer chemopreventive agent. The
Panax ginseng (Ginseng) is traditionally used in effects of β- lapachone on the growth of the human
most of the parts of world as a popular remedy for hepatoma cell line HepG2 were investigated. The
various diseases including cancer. It was reported that results showed that β-lapachone inhibits the viability
the ginsenoside Rp1, a compound isolated from ginseng, of HepG2 by inducing apoptosis, as evidenced by the
reduces cancer cell proliferation through inhibition of formation of apoptotic bodies and DNA fragmentation.
the insulin-like growth factor 1 receptor (IGF-1R)/Akt Reverse transcription-polymerase chain reaction and
pathway. Its efficacy was first tested against human breast immunoblotting results suggested that treatments of
cancer cell lines. The result showed treatment with Rp1 cells with β-lapachone resulted in down-regulation of
significantly inhibited breast cancer cell proliferation anti-apoptotic Bcl-2 and Bcl-XL and up-regulation of
and inhibited both anchorage dependent and independent pro-apoptotic Bax expression. β-Lapachone- induced
breast cancer cell colony formation. In addition, to apoptosis was associated with a proteolytic activation of
this treatment with 20 μM Rp1 causes cycle arrest and caspase-3 and -9 and degradation of poly (ADP-ribose)
apoptosis- mediated cell growth suppression. Findings polymerase protein. The study therefore indicated that
suggested that Rp1 reduced the stability of the IGF- 1R β-lapachone possess potential chemopreventive effect for
protein in breast cancer cells. Therefore, it is concluded liver cancer (Hyun et al., 2006).
that Rp1 has potential as an anticancer drug and that IGF-
1R is an important target for treatment and prevention of Vitis vinifera
breast cancer (Kang et al., 2011). Proanthocyanidins (PAs), also known as condensed
tannins, are naturally occurring oligomers and polymers
Pfaffia paniculata of flavan-3-ol monomer units widely found Grape seeds
Roots of Pfaffia paniculata have been well documented (Vitis vinifera L.) which have been used as nutritional
for several therapeutic effects and have also been used for supplements and, as antioxidants, to prevent atherosclerosis
cancer therapy in folk medicine. It anticancer activity and cardiovascular diseases. Proanthocyanidins shows
was evaluated against human breast tumor cell line and the anti mutagenic activity (De Rezender et al., 2009).
the MCF-7 cells. Butanolic extract of the roots of P. Antitumor and antioxidant activity of ethanolic extract
paniculata showed cytotoxic effect against MCF-7 cell of Vitis vinifera L. leaves were evaluated against Ehrlich
line. The results show that this butanolic extract indeed ascites carcinoma (EAC) induced in Swiss albino mice.
presents cytotoxic substances; further investigations are The antitumor effect and antioxidant role was determined
required to explore the active principle and its mechanism by using tumor volume, packed cell volume and estimation
of action (Nagamine et al., 2009). of liver LPO and antioxidant enzymes such as SOD, CAT.
Treatment with extract at a dose of 200 and 400 mg/kg
Polygonum multiflorum increased mean survival time, decreased the levels of LPO
Three anthraquinones, physcion, emodin, and questin and increased the levels of superoxide dismutase, catalase.
were isolated from the methanolic extract of the roots of The results suggest that ethanolic extract of Vitis vinifera
Polygonum multiflorum Thunb. (Polygonaceae). Research exhibited significant antitumor, antioxidant response in
revealed emodin and questin strongly inhibited the growth EAC tumor bearing mice (Mahadik et al., 2011).
of human colon cancer cells (Choi et al., 2007).
Conclusion
Ricinus communis
Ricin A is a newly isolated lectin from Ricinus Medicinal plants have been used for the cure of
communis which has a strong inhibitory effect on the different ailments including cancer for thousands of years.
growth of tumor cells. By using cell cultures, it was Large numbers of medicinal plants having anticancer
found that the tumor cells were more sensitive to lectin properties are available in nature but they are not fully
than non-transformed cells, and that this could be due phytochemially investigated. It should be of particular
4392 Asian Pacific Journal of Cancer Prevention, Vol 15, 2014
 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.11.4385
Medicinal Plants Combating Against Cancer - a Green Approach
interest to explore the anticancer potential of the medicinal 11, 101-13
plants extracts for isolation and characterization of the Hartwell JL (1982). Plants used Against Cancer. A survey
active anticancer principles so that better, safer and cost Lawrence, Massachusetts. MA. Quarterman Publications,
effective drugs can be developed for treating cancer. pp 438- 39.
Harvey AL (1999). Medicines from nature: are natural products
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