one of the major leading causes of death all over the world. For over 40years,
compounds originated from natural sources served at their best in combating
cancer. The biological metabolites obtained from marine world are considered to
be effective in cancer treatment. Another leading role of natural products
comes from plant alkaloids, terpenoids, flavonoids and steroids. Though a large
number of synthetic chemotherapeutic agents are available commercially, the
search for novel drugs is still an important goal for cancer therapy due to the
rapid development of resistance against these drugs. Most of the plant products
used in cancer treatment are not only involved in curing the disease, but also provoked
immunostimulant effects thereby improving the quality of life. Traditionally, the
medicinal plants with ability to prevent and hinder the progress of cancer are
in use. These plants maintain the vitality of individuals without causing toxic
This review is mainly focused on potentiality of herbal anticancer agents,
their mechanism of action and immunomodulatory effects of potent bioactive
constituents isolated from anticancer herbs.
anticancer, medicinal plants, phytochemicals, bioactive constituents, apoptosis
The world’s death rate due to cancer has
been increasing gradually. According to the estimates of International agency
for Research on Cancer (IARC), 14.1 million cancer cases and 8.2 million cancer
deaths were depicted worldwide. By the year 2030, cancer cases are expected to
grow to 21.7 million where as the cancer deaths to 13 million. Cancer, a
dreadful disease that can lead to death is hallmarked by cell proliferation, an
uncontrolled cell division and gene expression. There are nearly around 100
different types of cancers. Among them, breast and prostate cancers have shown
to be predominant in men and women. Although the etiology of the disease is not
known completely, a noteworthy research was done to treat the disease. Surgery,
chemotherapy, radiation therapy and immunotherapy are the different ways to
treat cancer. Chemotherapy involves anti metabolites, anthracyclines,
topoisomerase inhibitors, mitotic inhibitors, cell cycle regulators and
corticosteroid drugs. Besides curing the diseases, many of them induced adverse
side effects and are also immunosuppressants. However, therapies involving
natural compounds or their derivatives have played a beneficiary role in
combating cancer. The research for isolation of anti-cancer agents from
medicinal plants date back to 1950s which was initiated with the discovery of
vinca alkaloids (vincristine and vinblastine) and also with the discovery of
podophyllotoxin 1. An intensified research has undergone on several medicinal
plants; bioactive compounds and their wide range of applications in the fields
of medicine. Most of the plants have served as the best promising agents in
curing many diseases.
India is called the ?Botanical Garden
of the World” and is the abundant producer of medicinal plants. Ayurveda,
Siddha and Unani systems of medicine have paved the way for exploring these
medicinal plants and study of the bioactive constituents isolated from them. Pertaining
to the estimates, around 80-85% of world’s population relies on traditional
medicine for treating many diseases 2. With reference to the estimates,
approximately 50-60% of cancer patients in United States use bioactive agents
derived from plants with traditional therapeutic regimen such as chemotherapy
or radiation therapy. Earlier literature suggests that the Persons with
congenital immunodeficiencies had higher risk of developing cancers at 200
times than the expected frequency 3. Most
of the medicinal plants that are explored as anticancer ones, served as
immunomodulators also. Some of them include-Withania
somnifera, Curcuma longa, Andrographis
paniculata, Tinospora cordifolia, Allium sativum, Camellia sinensis, Zingiber officinalis, Nigella sativa,
Centella asiatica, picrorhiza kurroa, Aloe barbadensis and Momordica charantia 4. These
immunomodulators are known to enhance innate immune responses and can aid in
the protection of myelosuppressive effects of bone marrow caused during
conventional chemotherapy. The use of some potent immunomodulatory agents
isolated from plant sources has hindered the side effects and high cost of
plants as immunomodulatory leads:
It induced the
synthesis of monocyte chemo attractant protein-1 (MCP-1), TNF-?, IL-1? and
cyclooxigenase (COX-2). It decreased pancreatic ductal adenocarcinoma cell.
Inhibited polymorph nuclear leukocytes functions. Thymoquinine, a bioactive
constituent isolated from the seed exhibited immunomodulatory properties by
enhancing T-cell and natural killer cell mediated immune responses 5.
It has been used in
combination with variety of anticancer drugs .WS modulates the immune response,
increasing the expression of T-helper 1 (Th1) cytokines, as well as CD4 and CD8
counts, and natural killer (NK) cell activity 6.
The bioactive constituent curcumin,
acted as immunosuppressive agent. It inhibited T-helper 1(Th-1) cytokines in
CD4+ T-cells by down regulating IL-12 production in macrophages. This study has
suggested that curcumin can be used therapeutically in Th-1 mediated autoimmune
disorders. It also inhibited the production of IL-8, MCP-1(macrophage chemo
attractant protein), MIP-1? (macrophage inhibitory protein), IL-1? and TNF-?
acts as immunomodulator by enhancing phagocytic function without interfering
with cell mediated and humoral immune systems. Also caused inhibition of C3
convertase, component of classical complement pathway. Enhanced
activation of macrophages 8.
Shogaol in synergy with compound 6-gingerol exhibit immunomodulatory effects.
Tripathi et al, demonstrated that
6-gingerol inhibited the production of TNF-?, IL-1? and IL-12 in murine
peritoneal macrophages. Inhibition of pro-inflammatory cytokines like IFN- ?
and TNF-? resulted in reduction of nitric oxide production 9.
The extract has shown
immunostimulatory activity. It stimulated phagocytic activity and production of
It exhibits immunosuppressant activity by
reducing the production of NO and immunostimulatory activity by enhancing the
secretion of IL-2, IFN-? by T-cells, thereby inhibiting the growth of tumor. It
also increased Th-1 immune response 11.
The extract has
resulted in increase of phagocytosis of neutrophils and chemotactic locomotion
of neutrophils and also inhibited the production of TNF-? and IL-2 6, 12.
Studies on plant
suggest that it has immunostimulant property characterized by the elevation of both
cell-mediated and humoral mediated immune responses. It has shown a profound
effect on delayed type hypersensitivity reactions by releasing mediators of
hypersensitivity reactions 13.
cellular and humoral immune functions by inhibiting the production of TNF-? and
NO. Directly immunostimulates spleenic lymphocytes. The bioactive constituents
isolated from the plant can be used as immunomodulants to lessen
chemotherapy-induced immunosuppressive activities 14.
potent bioactive constituent isolated from the plant extract inhibited the increase
in expression of IL-6 and MCP-1.Reduces NF-?B activity. It also enhanced the
generation of pro-inflammatory mediators such as IL-12p70, IFN-? and TNF-?
The extract has
shown immunostimulatory effect by increasing total leukocyte counts and by
stimulating cellular and humoral immune functions. Inhibited the generation of
reactive oxygen species 16