Natural Products An Emerging Therapeutic Agent For Treatment of Cancer

10 | IJPRT | October – December
International Journal of Pharmacy Research and Technology
2012, Volume 2, Issue4, 10-14.
ISSN 2250 – 0944 (Online)
ISSN 2250 – 1150 (Print)
Review Article
Natural Products: An Emerging Theraputic Agents For Treatment of Cancer
Prajapati Rajendra*1
, Shah Chainesh1
, Ajudiya Keyur1
, Patel Milee1
, Patel Ayush2
1
R. H. Patel College of Pharmacy, Dahemi, Anand - 388001.
2
Sal Institute of Pharmacy, Ahmadabad.
*Corresponding Author: Email: raj199175@gmail.com
Received: 26/09/2012, Revised: 26/10/2012 Accepted: 25/012/2012
ABSTRACT
Cancer is being a life threatening disease which can prove to be fatal for an infected patient if proper care or treatment
is not taken in early stages. The cases of cancer are increasing day by day with the increase in the number of carcinogen. The
natural therapy is required to be adopted to reduce the toxicity to other cells associated with available allopathic treatment.
This review article mainly focuses on Natural products having various positive effects on the cancer cells and is very useful
in the treatment of various type of the cancer and in the death of various carcinogens. It has been proved that the natural
products show the reduction of growth of the cancer cells and other cytotoxic effect. Many of available drugs having the
capability to reduce the growth of cancer cells by 90% but having serious side effects to other cells and sometimes it may
leads to serious complications. Similarly many natural products have the ability of killing cancerous cells by 90% having
minimal or no side effects. The natural products such as beta-glucan, cat’s claw, vitamin C, mushroom extracts and various
herbs, etc are useful in the treatment of cancer and cost effective. When the proper combination of such natural products is
given it shows more potency to kill or inhibit growth of cancer cells and increase patient compliance by reducing treatment
of cost minimal side effects.
Keywords: Cancer, Carcinogen, Natural Products, Cytotoxic Effect, Cat’s Claw.
INTRODUCTION
The disease cancer is increasing at an enormous rate
and racing to the population rate. [1]
The main objective of
this review article is to understand the effect of the natural
products on the cancer cells by reduction in cell growth or
causing cell death and to acquire the knowledge if they are
more active than synthetic therapy. The Use of natural
therapy for the treatment of cancer which has very low
chances of side effects on the host cells of the human body.
Various natural products have ability to eradicate cancer
and can be used, which are easily available in a large
quantity and economical involving in unregulating cell
growth. In cancer, cells divide, rapidly and uncontrollably,
forming malignant tumors, and invade nearby parts of the
body. The cancer may also spread to more distant parts of
the body through the lymphatic system or bloodstream. Not
all tumors are cancerous, Benign tumors do not grow
uncontrollably, do not invade neighboring tissues, and do
not spread throughout the body. There are over 200
different known cancers that afflict humans. Determining
what causes cancer is complex. Many things are known to
increase the risk of cancer, including tobacco use, certain
infections, radiation, lack of physical activity, obesity, and
environmental pollutants. These can directly damage genes
or combine with existing genetic faults within cells to cause
the disease. Approximately five to ten percent of cancers
are entirely hereditary. [2,3,4]
Cancer is a disease characterized by uncontrolled
multiplication and spread of abnormal forms of the body’s
own cells. Cancer cells differs in four ways from the normal
cells. [2,4]
1. Uncontrolled proliferation
2. Dedifferentiation and loss of function
3. Invasiveness
4. Metastasis
Cancer occurs through changes in the DNA sequence
of our genome. Thus changes in the codon sequence keep in
progress as our body comes in contact with UV radiations
which can cause mutation. Cancer is mainly caused through
environmental causes like the carcinogens such as nitrogen
mustard, benzyl chloride, etc. sometimes it is caused by the
carelessness and addiction of the people like addiction of
chewing tobacco, smoking, etc and in few cases hereditary.
The environmental causes are way more in the number than
the hereditary. A mutation in signaling of the cell can send
error-causing signals to nearby cells which may cause cells
to become neoplastic, causing them to migrate and disrupt
more healthy cells. It may also cause the cell to become
immortal causing them to disrupt healthy cells forever.
Thus cancer can also be defined as continuous dividing of
the cells. Normal cells during division they pass through
various phases of cell division. During this they produce an
enzyme called telomerase which replaces the telomere. The
cells stop producing the telomerase enzyme but the
cancerous cells keep on producing this enzyme and do not
stop dividing. Normal cells do depend on their DNA
damage and cannot survive whereas cancer cells are
independent of DNA damage and thus they live further and
life span is more which creates tumors and mass.
[5,6,7,8,9,10,11]
Various class of anticancer drugs are being used
but they have severe adverse effect such as alkylating
agents such as Cisplastin is a good anticancer drug but it
has an adverse effect which leads to deafness.
Antimetabolites too have a large adverse effects such as
mucositis, thrombocytopenia, cirrhosis, etc. [2,3]
so if the
natural products are being used that would be much better
as the side effects would be less and if in any rural area is
there then it can taken as raw as the natural activity would
mostly depend on the active constituent present in that

Prajapati et al / International Journal of Pharmacy Research & Technology 2012 2(4) 10-14
IJPRT | October – December | 11
particular plant which we are going to use for the treatment
of cancer and some natural derivatives also helps in the
prevention of cancer as in some cases we don’t know the
etiology of the cancer because in many times the
environment causes are being seen so these chemical
constituents will help in prevention of development of any
cancer cells or preventing the normal cells from getting
infected. Almost 31 natural herbs and plants or natural
products are being used for the treatment of cancer which is
spinach, Astragalus, beta-glucan, Baikal skullcap, calcium
D-glucarate, cat’s claw, cesium, chlorophyll, Chrysin,
cordyceps, coriolus mushroom, etc[12,13,14,15,16,17]
.
Effect of Cancer on human body [2,3]
Infection due to cancer causes two genetic changes.
Out of which one is the activation of proto-oncogenes to
oncogenes due to which the control over cell division,
apoptosis and differentiation is lost. Another genetic change
which occur is inactivation of tumor suppressor genes due
to which the ability to suppress malignant change is lost.
Thus due to formation of such cells the functions of the
normal cells gets lost. The two types of tumors are being
seen- benign tumor and malignant tumor.
• Benign tumors causes destroying of hypothalamus,
atrial myxoma blocking the flow of blood through the
heart, meningiomas compressing the brain, colloid
cysts blocking the flow of cerebrospinal fluid, too much
of tumor causes a lot of pain, GI problems which causes
bleeding, potassium wasting, obstruction, hormone
production, torsion and infarction, etc
• Malignant tumors are of various types depending on
the site where they are forming and once they are
removed they are seen again but at different site. If any
of that cancer is not treated successfully it will
eventually kill the patient, causing edema, and different
type of this tumors show different effect on the body.
Natural products and their effect on the cancer cells
Generally three methods are being used for the
treatment of cancer which are surgery, radiation and
chemotherapy. In the chemotherapy generally the use of
various drugs is done such as alkylating agents, folic acid
analogs, Antimetabolites, natural derivatives, etc. now out
of all these class of anticancer drugs, the most interesting
study is done on natural derivatives. Various herbs, plants,
natural products such as spinach, Astragalus, beta-glucan,
Baikal skullcap, calcium D-glucarate, cat’s claw, cesium,
chlorophyll, Chrysin, cordyceps, coriolus mushroom, etc.
are being used in the treatment of the cancer. The
mechanism and effect of the natural products vary and so
their efficacy. Various natural products are showing the
following effect. It is estimated that there are 31 herbs and
natural products known used in treatment of cancer. [15,19]
Some of the natural products and there effects are shown in
Table: 1 as below:
Table 1: Effect of Different natural product on various types [15, 19, 20, 21]
Sr.
No.
Natural
Products
Cancer Type Effects
1.
Astragalus
saponins
Colon cancer
Inhibit cell proliferation through accumulation in S phse and G-2/M arrest,
it reduces the tumor volume as well as pro-apoptotic and anti-proliferative
effects
2. Beta-glucan Breast cancer
Obtained from mushroom and yeast and in wheat too, it helps in raising the
activity of the macrophage and NK cells in the body which helps In fighting
against the cancer cells. It also inhibits the hepatic metastases which inhibit
further growth of tumors and thus enhance long term survival of the patient.
3.
Baikal
skullcap
Leukemia, prostate,
lung cancer
Prevention of proliferation of malignant tumors, angiogenesis and causes
apoptosis.
4.
Calcium D-
glucarate
It has anticarinogenic properties in addition to glucuronidation. It generally
conjugates with the carcinogen or cancer cells and then they are excreted
through the biliary tract which is helpful during the treatment of cancer.
5. Cat’s claw Leukemia
It is helpful in treating feline leukemia virus. It is used to stimulate the
immune system. The oxindole alkaloids especially isopterodine and
pterodine stimulate phagocytosis.
6. Cesium Leukemia
Help in disappearance of pain in all patients within one to three days after
initiation of the treatment. It changes the ph from acidic to alkaline due to
which the pain sensation disappears.
7. Chrysin Breast cancer Aromatse inhibiting action which I helpful for women in breast cancer
8. Squalamine
Human ovarian
cancer, lung cancer.
Blocks blood vessels growth in tumors, it blocks the growth factor due to
which the growth of cancer cells either stops or reduces.
9. Fish oils Breast cancer
Immune system stimulation, tumor cell toxicity, alteration of cell
membrane.
10. Vitamin C
Lung cancer,
melanoma skin
cancer
It helps in killing the cancerous cells and also in inhibition of cancerous cell
growth.
Thus many such natural products such as chlorophyll,
honey, etc are useful in the treatment of cancer by cytotoxic
effect and inhibition of cell growth. The effects of the
natural products can be known and studied by performing
the following experiment where some mushroom extracts
and vitamin C is being used.
Official Bioassay of Determine the Cell Growth
Inhibition Activity of Natural Products: [22,23]
Various experiments regarding the effects of natural
products can be done in many ways but to show the effect
of natural products as they decrease the growth of the
cancerous cells. Experiment for determining the inhibition

of cancer cell growth. The following experiment will show
the effect of natural products to inhibit of cell growth.
Certain mushroom extract act on the bladder cancer
and reduces its growth. So Bladder cancer T24 cells are
being taken from the patient infected with transitional cell
carcinoma. These cells were maintained in McCoy’s 5a
medium which consists of 10% fetal bovine serum,
penicillin (100u/ml) and streptomycin (100microgram/ml).
The culture medium is changed after every 3-4 days and the
passage of cells was performed weekly. For experiments
these cells were seeded in six-well culture plates at an
initial cell density of 1x105
cells/ml. T24 cells were cultured
for 72 hours with varying concentration of different natural
products. Cell morphology, appearance, cell number and
viability can be checked using trypan blue exclusion test
and Alamar Blue cell viability test.
Trypan Blue Exclusion Test: [22,23]
In trypan blue exclusion test, trypan blue dye is being
used in the infected cancerous cells, the viable cells uptake
the dye and which shows a clear vision of the viable cells
and thus they can be differentiated. Thus by counting the
viable cells or general movement in the vision of the cells,
reading can be recorded.
Alamar Blue cell viability test: [22,23]
In Alamar Blue cell viability test, the alamar blue dye
is used for the cell viability test. 96-well plate is being used
in this test. You can examine 50 cells per well. Serial
dilution of alamar blue is done at 1/10 volume in black,
clear bottom 96-well plates and fluorescence was measured
after 40 minutes and 18 hours. The effect of the natural
products depends on the intensity of fluorescent light
emerging from the 96-well plate. It works on the
mechanism that it contains resazurin, a non fluorescent
indicator dye, is converted into highly red-fluorescent
resorufin via redox reactions in metabolically active cells.
Thus it indicates the number of the active and living cells.
The following natural products are being tested by the
above experiment and the study of their effect on the
cancerous cells was being observed.
1) Active fraction of maitake mushroom
2) Extract of meshimakobu mushroom
3) Extract of yeast cell wall
4) Extract of Agaricus blazei Murill mushroom
5) Arabinoxylan from rice bran
6) Mixed powder of Agaricus blazei Murill mushroom and
shark cartilage
7) Mixed powder of three kinds of mushrooms and three
herbs
8) Mycelial extract of several mushrooms
9) Vitamin C
These natural products are being tested one after
another on the cancerous cells and the concentration of
them is varied too and the following effect is shown by
some of the natural products on the cancerous cells.
Sometimes to obtain better result in the effect on the cancer
cells the combination of the natural products can be given.
The results show in the following table-2.
Table 2: Results of various Natural Products with their Different Effective Concentration and Effects [24]
Sr.
No.
Natural product Effective Concentration Effect
1
Active fraction of maitake
mushroom
60 µg/ml
120 µg/ml
≥ 240 µg/ml
No effect
25% reduction in cell growth
≥ 90% reduction in cell growth
2
Extract of meshimakobu
mushroom
20 µg/ml
50 µg/ml
100 µg/ml
≥ 200 µg/ml
No effect
≥ 90% reduction in cell growth
3 Vitamin C
100 µM
200 µM
300 µM
500 µM
700 µM
1000 µM
No effect
No effect
No cell growth
4 Extract of yeast cell wall 20 µg/ml ≥ 90% cell death
All the above mentioned natural products showed
reduction in the growth of cancerous cell. The other natural
products such as Extract of Agaricus blazei Murilll
mushroom, Arabinoxylan from rice bran, Mixed powder of
Agaricus blazei Murill mushroom and shark cartilage,
Mixed powder of three kinds of mushrooms and three herbs
show very little effect even when they are used in high
concentration.
Etiology [25]
Cause that is not inherited genetically, not merely
pollution.Common environmental factors that contribute to
cancer death include tobacco (25–30%), diet and obesity
(30–35%), infections (15–20%), radiation (both ionizing
and non-ionizing, up to 10%), stress, lack of physical
activity, and environmental pollutants. Substances that
cause DNA mutations are known as mutagens, and
mutagens that cause cancers are known as carcinogens.
Many mutagens are also carcinogens, but some carcinogens
are not mutagens. Alcohol is an example of a chemical
carcinogen that is not a mutagen.
Some hormones play a
role in the development of cancer by promoting cell
proliferation. Hormones are important agents in sex-related
cancers such as cancer of the breast, endometrium, prostate,
ovary, and testis, and also of thyroid cancer and bone
cancer. Excepting the rare transmissions that occur with
pregnancies and only a marginal few organ donors, cancer
is generally not a transmissible disease.
Pathogenesis [25]
Cancer occurs when a single progenitor cell accumulates
mutations and other changes in the DNA, histones, and

IJPRT | October – December | 13
other biochemical compounds that make up the cell's
genome. The cell genome controls the structure of the cell's
biochemical components, the biochemical reactions that
occur within the cell, and the biological interactions of that
cell with other cells. Certain combinations of mutations in
the given progenitor cell ultimately result in that cell (also
called a cancer stem cell) displaying a number of abnormal,
malignant cellular properties that, when taken together, are
considered characteristic of cancer, including:
• The ability to continue to divide perpetually, producing
an exponentially (or near-exponentially) increasing
number of new malignant cancerous "daughter cells"
(uncontrolled mitosis);
• The ability to penetrate normal body surfaces and
barriers, and to bore into or through nearby body
structures and tissues (local invasiveness);
• The ability to spread to other sites within the body
(metastasize) by penetrating or entering into the
lymphatic vessels (regional metastasis) and/or the blood
vessels (distant metastasis).
If this process of continuous growth, local invasion,
and regional and distant metastasis is not halted via a
combination of stimulation of immunological defenses and
medical treatment interventions, the end result is that the
host suffers a continuously increasing burden of tumor cells
throughout the body. Eventually, the tumor burden
increasingly interferes with normal biochemical functions
carried out by the host's organs, and death ultimately
ensues.
Mycelial extract of several mushrooms but when they
were used with another natural product such as Vitamin C,
it showed better effect and it helped in killing the cancerous
cells (cytotoxic effect) as shown in Table-3
Table 3: Effect Vitamin-C and Active Extracted fractions
of several Mushrooms with their effects [26]
Vitamin- C
Active
fraction of
Maitake
Mushroom
Extract of
Meshimakobu
Mushroom
Effect
200 µM 30 µg/ml -
› 90% cell
death
200 µM - 20 µg/ml
› 90% cell
death
Thus the above experiment explains the property of
natural products of inhibiting cell growth and cytotoxic
effect by causing the cell death. Some of the natural
products show the cytotoxic effect whereas some are useful
in inhibition of the growth of the cancerous cells.
Some of the above natural products such as mushroom
extract and vitamin c show effects on the cancerous cells.
Active fraction of Maitake mushroom and Extract of
Meshimakobu mushroom when inserted in the cancerous
cells shows their effect. It was observed that the intensity of
fluorescent in Alamar blue dye test was decreasing with the
increase in the concentration of the natural products which
shows that there was depletion in the growth of the cancer
cells. They mainly cause the inhibition of the growth of the
cancer cells. As the concentration of these natural products
increases, the effect increases and there in reduction in the
growth of cancerous cells to a great extent. Both of them
were required in amount of 240µg/ml and 200µg/ml
respectively for causing 90% reduction in growth of cancer
cell but when they were used in combination with vitamin
C they were used 30 µg / ml and 20 µg / ml respectively to
cause 90% cell death. Vitamin C itself doesn’t give
cytotoxic effect but in combination with active fraction of
Maitake mushroom and extract of Meshimakobu mushroom
it gives the cytotoxic effect. Therefore when used in proper
combination of natural products for the treatment of cancer,
it is proved to be more efficient and potency becomes high
whereas extract of yeast cell wall directly gives the
cytotoxic effect on the cancerous cells. Thus these natural
products can be very useful in the treatment of cancer as the
side effect is less. [26]
From the experiment which was being performed, it
was concluded that natural products do have some effect on
the cancer cells in the body of an infected person. From the
result it was shown that natural products do show two main
promising effects on the cancer cells
A. They inhibit the proliferation of the cancer cells which
results into the inhibition of the growth of the cancer
cells.
B. They show cytotoxic effect due to which the activity of
macrophage and NK cells increases which helps in
killing the cancerous cells from the body. [27,28]
CONCLUSIONS
Natural products are emerging novel approach for the
treatment of cancer and enlarge the fields of pharmaceutical
researchers. It can be predicted that the exercise of natural
product in the treatment of cancer is favorable, due to other
available treatment in the market employed with high
treatment cost and chances of severe side effects by acting
on other than cancerous cells which causes some serious
complications comparing to natural product. Evan use of
natural product in treatment of cancer is cost effective
because it is extensively available so it is affordable by
patients and hence increases patient’s compliance.
REFERENCE
1. Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman
D. Global cancer statistics. Cancer journal for
clinicians. 2: 69–90 (2011).
2. Rang H, Dale M., Ritter J, Flower R. Rang and Dale’s
Pharmacology. 6th
Ed. 2006; 647-53.
3. Danaei G, Vander Hoorn S, Lopez AD, Murray CJ,
Ezzati M. Causes of cancer in the world: comparative
risk assessment of nine behavioural and environmental
risk factors. Lancet; 366 (9499): 1784–93 (2005).
4. Khalil A. Bioresources cell walls of tropical fibres.
2006; 220-32.
5. Seitz H, Pöschl G, Simanowski U. Alcohol and cancer.
Recent Dev Alcohol; 14: 67–95 (1998).
5. Berrington D, González A, Mahesh M, Kim K,
Bhargavan M, Lewis R, Mettler F, Land C. Projected
cancer risks from computed tomographic scans
performed in the United States in 2007. Arch. Intern.
Med; 169(22): 2071–7 (2009).
6. McCulley M, Greenwell P. Molecular therapeutics:
21st-century medicine. London: J. Wiley 2007; 207.
7. Gwyn R. Researching and applying metaphor.
Cambridge University Press.1999.
8. Sulik G. Pink Ribbon Blues: How Breast Cancer
Culture Undermines Women's Health. New York:
Oxford University Press. 2010; 78–89.

9. Rostom A, Dubé C, Lewin G, Tsertsvadze A et al,
Nonsteroidal anti-inflammatory drugs and
cyclooxygenase-2 inhibitors for primary prevention of
colorectal cancer: a systematic review prepared for the
U.S. Preventive Services Task Force. Ann. Intern. Med;
146 (5): 376–89 (2007).
10. Sasco A, Secretan M, Straif K. Tobacco smoking and
cancer: a brief review of recent epidemiological
evidence. Lung Cancer 45; 2: 3–9 (2004).
11. Smith T, Hillner B. Bending the Cost Curve in Cancer
Care. New England J. Medicine; 364 (21): 2060-5
(2011).
13. Kemper K. Cat’s claw. A Brief review on long wood
herbal. Task force 1999; 3-9.
14. Konno S. Effect of natural products on growth factors
of bladder cancer cells. Alternative Medicine Review;
12: 63-68 (2007).
15. Montbriand M. Herbs and natural products effects.
Oncology Nursing Form; 31(4): 75-90 (2004).
16. Levy M, Back A. National Comprehensive Cancer
Network- Palliative care and Clinical practice
guidelines in oncology. J. National Comprehensive
Cancer Network; 4 (8): 776–818 (2006).
17. Arroo R. Breast cancer research. New England J.
Medicine; 10(3): 3-5 (2011).
18. Min-Hsiung P, Chi-Tang H. Chemopreventive effects
of natural dietary compounds on cancer development.
19. Egner P, Munoz A. Chemoprevention with
chlorophyllin in individuals exposed to dietary
aflatoxin. Mutat Res; 209-216 (2003).
20. Kephart J. Chlorophyll derivatives-their chemistry,
commercial preparation, and uses. Econ. Botany; 9: 3-
38 (2003).
21. Edwards B. Treatment of chronic leg ulcers with
ointment containing soluble chlorophyll.
Physiotherapy; 40(6):177-9.
22. L´opez J, Del E. A database for the dereplication of
natural product mixtures in bioassay-guided protocols.
Bioinformatics; 23(23): 3256–7 (2007).
23. Guiseppe S, Sadam G, Banerjee D, Bertino J.
Cytotoxicity and cell growth assays. Cell biology: 315-
22.
24. Pieters L, Vlietinck A. Bioguided isolation of
pharmacologically active plant components, still a
valuable strategy for the finding of new lead
compounds. J Ethnopharmacol; 100: 57–60 (2005).
25. Henderson B, Bernstein L. Hormones and the Etiology
of Cancer. Cancer Medicine; 5: 113-1 (2011)
26. Dwivedi C, Heck W, Downie A. Effect of calcium
glucarate on beta-glucuronidase activity and glucarate
content of certain vegetables and fruits. Biochem Med
Metab Biol; 43: 83-92 (1990).
27. Kang N, Zhang J. Induction of G (2) / M phase arrest
and apoptosis by oridonin in human laryngeal
carcinoma cells. J Nat Prod; 73: 1058-63 (2010).
28. Wang W, Porter W. Mechanism of inhibition of MDA-
MB 468 breast cancer cell growth. Carcinogenesis
1997; 18: 925-33.

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