Panax or Korean Red Ginseng and Cancer

Effects of Panax or Korean Red Ginseng on Cancer

Red or Panax ginseng is used in traditional Chinese medicine as a prophylactic, a stimulant, and a
treatment for various diseases. In addition, ginseng has been found to enhance the immune
system and possess an anti-tumor effect. Ginseng appears to stimulate humoral and cellmediated
immune responses and the subsequent increase in titers of lymphocytes and circulating
antibodies. Furthermore, ginseng's cancer-prevention properties seem to be mediated through
the increased production of interferons and cytokines, which activate natural killer and cytotoxic
T-cells that can served to lyse or inhibit growing tumors. Both clinical and epidemiological studies
indicated that Panax ginseng can reduce the incidence of cancer in vivo. These results suggest
that ginseng shows antitumor effects as an immunomodulator.

Introduction
Korean Red (Panax) Ginseng is a traditional Chinese medicinal herb that has occupied an esteemed
position among the tonic medications since antiquity and has become quite popular
among the patrons of health food stores. The term ginseng means "essence of man"
because it has been touted as a revitalizing agent. Ginseng has been used for several
thousands of years in the Orient as a tonic, prophylactic agent, and restorative. Other
people have found that it enhances the immune system and possess anti-tumor effects.
Recent studies have reported that saponin from Panax ginseng protects against
myocardial and cerebral ischemic damage in different animal models (1).

Perhaps one of the most fascinating and potentially therapeutic effects of Panax ginseng
is its ability to enhance the immune response in the body. Recent studies have
investigated the effects of ginseng on the immune system in order to find new possible
components that may support the treatment of infectious and immunodeficient diseases.

Ginseng has been shown to slow growing tumors and inhibit the incidence of lung
adenoma (6). In epidemiological studies, ginseng uptake reduces the incidence of human
cancer (6). It has been suggested that ginseng may increase activity in the nonspecific
resistance of an organism to combat tumor growth. This paper will evaluate the effects of
ginseng on the immune system in animal studies and recent clinical evaluations. Perhaps
by understanding the effects of Panax ginseng, we can study its possible effects of
preventing cancer.

Immuno-mediating Effects
The landmark paper which first evaluated the effect of ginseng extract on the expression
of humoral and cell mediated immune responses showed that the number of antibody
forming cells, as well as the titers of circulatory antibodies, are enhanced if test animals
are pretreated with ginseng extract. On the fourth day after the injection of the antigen
(sheep's red blood cells) in mice, the antibody titer of the ginseng treated group was twofold
higher than that of the control group; on the tenth day, the treated group showed a
four-fold higher titer. They also had data that showed elevated natural killer (NK) cell
activity in comparison to control animals. These experiments led the way in determining
ginseng's immunostimulatory effects (7).

The use of polysaccharides from plants and herbs as immunostimulants has aroused great
interest in recent years. Immunotherapy is currently receiving great attention as support
treatment modalities in the management of cancer and AIDS patients whose immune
function is compromised. The polysaccharides extracted from Panax ginseng have been
investigated to determine their effects on the immune system. These polysaccharide
fractions were all tested for their anticomplementary activities using human serum and
antibody-sensitized sheep RBC. Complement systems play an important role in fighting
against various infections and tumors. Those active polysaccharides were found to be
able to stimulate the complement system possibly by enhancing the production of
interferon y (INF-y) by activated T-cells. INF-y is important in immune defense against
various viral infections and in the regulation of cell-mediated immune response.
Interferons are secreted by an infected cell as an early, non-specific defense before
specific antibodies appear. Interferons can protect uninfected cells by stimulating the
production of proteins that inhibit viral replication. Furthermore, the defense is not virus specific;
interferons produced in response to one viral strain confer resistance to unrelated
viruses. Thus, interferons are most effective in controlling short-term infections, such as
cold and influenza. This effect of ginseng is confirmed by Scoglione et al. (11) which
shows that a standardized extract of ginseng could induce a higher immune response in
vaccination against influenza.

 In a randomized, placebo controlled, double blind investigation of 227 volunteers, the frequency of influenza or the common cold was significantly less (p<0.001) in volunteers who received daily oral doses of ginseng as opposed to a placebo group (11). By the eighth week, antibody titers rose to an average of 272 units in the treatment group as opposed to 171 units in the placebo group (p<0.0001).
At concentrations from nanomolar to low micromolar range, ginseng polysaccharides can
significantly induce the production of TNF-a by mouse peritoneal macrophages (8). TNFa
has profound effects in the immune system, including tumor, cytotoxic, antiviral, and
anti-parasitic activities. TNF-a also causes inflammation and endotoxic shock, which may
be responsible for some possible side effects of polysaccharides. Thus, one of the
hypothesized activities of ginseng extracts is that they stimulate the complement system
by enhancing the production of INF-y and TNF-a .

Ginseng has also significantly enhanced natural killer cell function, which is part of the
body's nonspecific defense mechanisms. The ability of ginseng to boost NK cell activity
hints at its cancer preventive mechanisms. NK cells do not attack microorganisms
directly, but rather destroy the body's own infected cells. The NK cells also assault and
lyse aberrant cells that could form tumors. Peripheral blood mononuclear cells (PBMC)
either from normal individuals or from patients with either AIDS or chronic fatigue
syndrome (CFS) were treated with increased concentration of Panax ginseng extract. For
each group, increased concentrations of the herb progressively increased both the
antibody dependant cellular cytotoxicity and natural killer cell function (9). The presence
of ginseng extract significantly enhanced NK-function by PBMC from normal controls at
concentrations of greater than 10 ug/ml and cells from patients with either CFS or AIDS
at concentrations of greater than 1 ug/ml. Thus, extracts of Panax ginseng enhance
cellular immune function of PBMC both from normal individuals and patients with
depressed cellular immunity. NK cells have been demonstrated to lyse HIV infected cells
(10). If the clinical efficacy of immune stimulation in CFS and/or HIV-infected patients
were eventually demonstrated, the use of immune modulators may be an attractive
therapeutic alternative.

Even in healthy individuals, ginseng has been shown to be an immunopotentiating agent.
A controlled, double-blind study with standardized Panax ginseng extract against a
placebo found that a randomized group of 60 healthy volunteers given ginseng showed
significant increases in chemotaxis and NK activity as well as rises in phagocytosis
function (12). This group also demonstrated significant (p < 0.001) increases in total
lymphocytes (T3) and helper T4 percentages after consuming a capsule (100-mg ginseng
extract) every 12 hours for eight weeks. These data show that ginseng extracts are able to
stimulate an immune response in humans.

Isolated fractions of an immunomodulator from ginseng were used to test its tumor
inhibitory activity. Ethanol-insoluble extracts of ginseng were first demonstrated to
generate active killer T- cells through endogenously produced IL-2 (13). Peripheral blood
lymphocytes derived from humans or animals can be activated by IL-2 and become
highly cytotoxic against various malignant cells. IL-2 is a cytokine that signals other
lymphocytes to grow and proliferate. Thus, they can increase the supply of T
lymphocytes that can differentiate into cytotoxic T-cells. Because cancer cells carry
distinctive non-self molecular markers, cytotoxic T-cells can target the cancer cells and
lyse them. The injection of IL-2 can therefore mediate regression of selected metastatic
tumors in mice and humans. Yun et al. tested whether the endogenously produced IL-2
mediated the in vivo anti-tumor activity through the activation of lymphocytes (14).
Isolated IL-2 fractions that activated natural killer cells were tested in a benzo[a]pyrene
(BP) induced autochthonous lung tumor model. BP is an environmental carcinogen. The
incidence of lung tumor in the BP alone group was 55% at the ninth week after BP
treatment and it was significantly deceased by the treatment with ginseng extract. The
incidence decreased by 60% (p<0.05) in mice concurrently administered drinking water
containing 2 mg/ml ginseng extract for 6 weeks(14). The inhibition of lung tumor
incidence was dose dependent, indicating that ginseng can have specific effects that can
be augmented by increasing concentrations. Furthermore, Yang (15) found that injection
of ginseng partially restored the number and colony of activity in bone marrow cells,
which significantly enhanced the production of interleukin-1, interleukin-3, and
interleukin-6 like substances from immune cells.
Since 1978 Yun et al. have set out to investigate if ginseng can inhibit carcinogenesis.
These researchers demonstrated that Panax ginseng extract has anticarcinogenic effects
against pulmonary tumors induced by various chemical carcinogens. Mice injected
subcutaneously with BP within 24 hours of birth and which continued to receive ginseng
extracts in drinking water showed a significant decrease in incidence of lung adenoma.
This report is consistent with the anticarcinogenic effects of Korean Red or Panax ginseng described
earlier. These researchers then began a human case-control study to further determine the
effect of ginseng consumption in cancer resistance. In a recent study of almost 2,000
patients and matched controls in the Korea Cancer Center, ginseng intake resulted in a
decreased risk for cancer (odds ratio= 0.5) (16). In addition, their results showed a
decreased risk with rising frequency of ginseng intake.


Conclusion
Ginseng has been used for nearly 2,000 years for its prophylactic and anti-tumor effects.
Also, as Panax ginseng sales and public use continue to grow nationally, it is important to
encourage efforts to study the efficacy of ginseng in humans.
The results of the above experiments and epidemiological studies confirm that Panax
ginseng has various anticarcinogenic and immunomodulatory effects. While the exact
mechanism of ginseng pharmacology remains to be solved, these studies suggest that
Panax ginseng contains ingredients that stimulated humoral and cell mediated immune
responses. Enhanced production of interferons can help to inhibit viral replication,
helping to prevent infection. Increased antibody and lymphocyte titers may be very useful
in helping cancer and AIDS patients, whose immune functions are compromised.
Stimulating NK can cytotoxic T-cell activity can lyse and help fight or prevent against
growing tumor cells. These promising results may perhaps one day offer a powerful
adjunct to immuno- and cancer therapy.

REFERENCES
1. Chen X. Cardiovascular protection by ginsenosides and their nitric oxide
releasing action. Clinical and Experimental Pharmacology and Physiology
1996;23:728-732.
2. Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulindependant
diabetic patients. Diabetes Care 1995;10:1373-1375.
3. Kwan CY. Vascular effects of selected antihypertensive drugs derived from
traditional medicinal herbs. Clinical and Experimental Pharmacology and
Physiology 1995;1:297-9.
4. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochemical
Pharmacology 1997;54:1-8.
5. Engels HJ, Wirth JC. No ergogenic effects of ginseng (Panax Ginseng C.A.
Meyer) during graded maximal aerobic exercise. Journal of the American Dietetic
Association. 1997;97:1110-5.
Nutrition Bytes, 4(1), Article 7 (1998)
6. Yun TK. Experimental and epidemiological evidence of the cancer-preventive
effects of Panax ginseng C.A. Meyer. Nutrition Reviews 1996;54:S71-S81.
7. Singh VK, Agarwal SS, Gupta BM. Immunomodulatory Activity of Panax
ginseng extract. Planta Medica 1984;6:462-465.
8. Gao H, Fengzhen W, Lien EJ, Trousdale MD. Immunostimulating
Polysaccharides from Panax notoginseng. Pharmaceutical Research
1996;13:1196-1200.
9. See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng
on natural killer and antibody-dependent cell cytotoxicity in health subjects and
chronic fatigue syndrome or acquired immunodeficiency syndrome patients.
Immunopharmacology 1997;35:229-235.
10. Jenkins M, Mills J, Kohl S. Natural killer cytotoxicity of human
immunodeficiency virus-infected cells by leukocytes from human neonates and
adults. Pediatric Research 1993;33:469-474.
11. Scoglione F, Cattaneo G, Alessandria M, Cogo R. Efficacy and safety of the
standardized ginseng extract G115 for potentiating vaccination against common
cold and/or influenza syndrome. Drugs Under Experimental and Clinical
Research 1996;22:65-72.
12. Scoglione F, Ferrara F, Dugnani S, Falchi M, Santoro G, Fraschini F.
Immunomodulatory effects of two extracts of Panax Ginseng C.A. Meyer. Drugs
Under Experimental and Clinical Research 1990;16:537-542.
13. West WH, Tauer K, Yannelli JR, Marshall GD, Orr DW, Thurman GB, Oldham
RK. Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of
advanced cancer. New England Journal of Medicine 1987;316:898-905.
14. Yun YS, Lee YS, Jo SK, Jung IS. Inhibition of autochthonous tumor by ethanol
insoluble fraction from Panax ginseng as an immunomodulator. Planta Medica
1993;59:521-524.
15. Yang G. Immunologic effect of traditional Chinese drugs. Chinese Medical
Journal 1996;109:590-60.
16. Yun TK, Choi SY. Preventive effect of ginseng intake against various human
cancers: A case-control study on 1987 Pairs. Cancer Epidemiology, Biomarkers,
and Prevention 1995;4:401-408.