Cancers are a scourge of modern society. Cancers attack the fundamental life processes of the cells, normally altering the total genetic complement or genome of the cell with mutation of one or more genes or fracture of a segment or segments of the DNA strand or loss of segments of the chromosomes. Mutation may occur by chance but other factors can initiate cancer development e.g. specific chemicals known as carcinogens, ionizing radiations, physical irritation, hereditary pre-disposition and certain viruses. The resultant cancer cell overgrows, that is, it is not constrained in its growth by naturally-occurring chemical limiters called chalones. In addition cancer cells tend not to adhere to one another and can therefore stray freely around the body via the blood and lymph systems and can set up new cancerous centres or metastases which are commonly known as secondaries. There is accumulating evidence that malignant transformation of a cell, be it blood, lung or brain, is due to the change of particular genes and emphasises the need for the development of highly sequence-selective DNA-interacting drugs. Protein kinase C (PKC), a Ca++/phospholipid-activated protein kinase, is a cell biopolymer controlling many cell functions by selective protein threonine/serine phosphorylation in the presence of adenosine triphosphate. When PKC is out of control there is a series of signals leading to the uncontrolled cell proliferation typical of cancer.
The cancerous condition develops frequently in patients manifesting reduced resistance as in old age and such cancers can be combatted by strengthening the general body resistance whilst simultaneously treating the cancer with suitable drug therapy or appropriate radiation treatment. Therefore adaptogens such as ginseng or eleutherococcus should function well by stress resistance and antitoxic effect. Ginseng enhances the formation of antibodies and immune functions in cancer patients and in microbe-infected experimental laboratory animals, possibly by elevation of the cAMP (cyclic adenosine monophosphate) levels. Both antitumoral activity and stimulation of the immune function of cancer patients when ginseng was administered have been observed in experimental animals and in human subjects. The reduced susceptibility of the host to bacterial, viral or tumour attack or infection has been referred to as "non-specific immunostimulation", "para-immunity" or "biological response modification (BRM)" (Sonnenborn, 1987). A wide range of disparate plant and pharmaceutical agents has been suggested as inducers including 2-mercapto-ethanol derivatives, synthetic compounds such as cimetidine and levamisole, some peptides from human casein hydrolysate, ^-1,3-glucans, extracts of the thymus gland, plant extracts from families such as Loranthaceae (e.g. Viscum album L., Mistletoe), Echinaceae (e.g. Echinacea spp., Coneflowers), Compositae (e.g. Silybum marianum (L.) Gaertn., Milk Thistle), Araliaceae (e.g. Eleutherococcus senticosus Maxim., Siberian ginseng; Panax spp., ginsengs), etc., etc.
Mitchell (1985) stated that a substance considered as a Biological Response Modifier should fulfil one or more of the criteria:-
1) a compound or preparation reacting to the tumour by either raising the count or activity of the effector cells or stimulating production of the mediator (e.g. interferons, a class of proteins inhibiting the growth and multiplication of viruses in cells, and lymphokinins associated with the T lymphocytes of the thymus gland);
2) a substance that functions as an inhibitor of the immune system suppression system and thus stimulates the individual body defence mechanism indirectly;
3) a compound that elevates or stimulates the immune defence system and therefore functions as a positive inducer or mediator;
4) a substance increasing tolerance to cytotoxic antitumour therapy by encouraging leucocyte proliferation in the bone marrow;
5) a compound modifying the surface area of the tumour cells so that the effectiveness of cytotoxic medicaments is increased or the capacity for metastase formation is reduced;
6) a substance inducing cell transformation that will arrest, cancel, reverse or discriminate against the "primitive tumour cell".
Considering these stated criteria it is clear that ginseng has potential as a supporting agent in classical cancer therapy. The investigation of ginsengs as potential anticancer agents was undertaken by Russian pharmacologists in the 1960's and 1970's. Under experimental conditions preparations of ginseng, particularly ethereal and alcoholic extracts, and isolated ginsenosides were shewn to inhibit urethane-induced adenomas of the lung, 6-methyl-thiouracil-induced tumour of the thyroid gland and indole-induced myeloid leukaemia in laboratory animals. It was realised that ginseng could decrease the transplantability and size of tumerous foci when cells of Ehrlich's ascitic tumour were introduced intravenously into mice. The formation of spontaneous tumours of mammary gland and spontaneous leukaemia in mice could also be reduced although leukaemia-L1210 tumours were unaffected (Hou, 1978). Investigating the inhibitory effect of the phytoadaptogenic drugs bioginseng, Eleutherococcus senticosus and Rhamnus carthamoides on the growth of tumours induced by N-nitrosoethylurea on the nervous systems of rats, Bespalov et al. (1992) observed that all three drugs prolonged life and reduced the size and frequency of the tumours and that ginseng possessed the greatest anticarcinogenic activity and Eleutherococcus the least.
Therefore ginseng was apparently potentially useful in the attack on neoplasms or tumours such as adenomas (benign glandlike tumours), carcinomas (malignant cancers of the lining tissues of the skin and internal organs), leukaemias (malignant disorders of the white blood cells), melanomas (pigmented tumours which may become malignant due to the overgrowth of melanin-producing cells in the basal layers of the skin) and sarcomas (malignant tumours of the connective tissues of bone, muscle or tendon).
Despite the promising observations of the early workers, some pharmacologists questioned the methodology employed and doubted the validity of the results obtained. Nevertheless, as cancers tend to develop in persons with lowered resistance, any preparation or substance with the ability to bolster the immuno-defence system should retard cancer initiation. Better designed experiments shewed that ginseng saponins increased phagocytosis in the tissue macrophage (reticuloendothelial) systems of normal and tumour-infected mice and stimulated cellular and humoral immune function but, as yet, no satisfactory explanation of this immunomodulatory action has been presented.
Early work shewed that light petroleum and ethyl acetate fractions of ginseng root extract effectively inhibited the in vitro growth of mouse leukaemia L5178Y and mouse sarcoma S180 cells in a dose dependent manner. The toxic effect on the cancer cells was correlated with an inhibitory action on macromolecule biosynthesis, the light petroleum fraction in particular inhibiting protein synthesis whilst the ethyl acetate fraction inhibited certain RNA species (Yun et al., 1980).
Ginsengs have been proposed as oral antitumour agents, the ginsenosides Rb1 and Rg1 being specifically implicated. Activity was claimed against a range of tumours in human subjects as well as in laboratory animals; for example, treatment of mice bearing the sarcoma S180 with 50 mg/kg of ginsenoside Rg1 for 7 days yielded a 52 per cent tumour inhibition (Arichi et al., 1982). The subcellular organelles of Morris hepatoma cells grown in a culture medium containing ginsenosides were observed to be well developed with a well-organised distribution when compared with untreated control cells. Thus ginsenosides could reverse the transformation of Morris hepatoma cells (Odashima et al., 1979). Following on this work it was noted that ginsenoside Rh2 was incorporated into the cell membranes of B16 melanoma skin cancer cells and erythrocytes and the fluidity of the cell membranes was modified as determined by polarisation changes of the cells labelled by 1,6-diphenyl-1,3,5-hexatriene. It was suggested that this phenomenon was related to the phenotypic reverse transformation of the cancer cells (Ohta et al., 1985). The effects of ginsenosides Rh1 and Rh2 were then studied employing mouse melanoma B16 cells in culture. In a concentration dependent manner ginsenoside Rh2 inhibited the growth of the B16 cells at 5-15 |M concentration, initiating morphological changes and stimulating melanin synthesis at high cellular densities. On removal of ginsenoside Rh2 after 2-6 days, the cellular growth rate recovered slightly although incompletely during the next four day period of experiment. Although 20(S)- and 20(R)-ginsenosides Rh1 did not inhibit growth of B16 cells, they, like ginsenoside Rg3, did stimulate melanin synthesis in a concentration dependent fashion (Tahara et al., 1985). Ginsenoside Rh1 did not inhibit growth even at a concentration exceeding 100 |M but it did stimulate expression of the melanotic phenotype. Significantly ginsenosides Rh1 and Rh2 vary only in the possession of a glucose unit at C-6 and C-3 respectively but differ markedly in their effects on B16 melanoma cells; this may be related to the occurrence of ginsenoside Rh2 in the lipid fraction of the B16 melanoma cell membrane whilst ginsenoside Rh1 was not so detected (Odashima et al., 1985). Ginsenoside Rh2 was also found to cause flattening of cells cultured in a collagen gel with resultant development of non-overlapping monolayers as well as markedly increased adhesiveness of cell to cell and cell to substrate, factors which tend to reduce the spread of cancers. Ginsenoside Rh1 did not produce such effects (Ohta et al, 1987). Chen et al. (1988) isolated the related compound 20^-ginsenoside Rh2 from the stems and leaves of P. ginseng and reported that at 2 g/mL concentration the growth of human leukaemia cell line HL-60 was inhibited. Subsequent work confirmed that ginsenoside Rh2 has strong affinity for the lipid layer and is quickly absorbed into the cell membrane lipid bilayer altering the layer and thus affecting certain functional molecules on the cell surface. Therefore glycosidase glucosyl transferase, receptor protein and adhesion protein may be affected by ginsenoside Rh2, changing signals or their transmission to the nucleus. Consequently the expression of certain genes, such as c-myc oncogene, changes although ginsenoside Rh2 does not act directly on the expression of c-myc oncogene which is probably regulated at the level of protein synthesis and/or protein stability and c-myc proteins express at every phase in the cell cycle of the cancer cell lines examined. Certainly ginsenoside Rh2-treated cancer cells expressed a phenotype closer to that of their normal counterparts (Ohta et al., 1990). Ginsenoside Rh2 has also been shewn to retard the growth cycle of S180 sarcoma tumour cells from the S period to the G2 period in mice; ginsenoside Rh1 did not demonstrate the same effect (Ma et al., 1991).
Kikuchi and his colleagues (1991) studied the in vitro and in vivo effects of the diol-type ginsenoside Rh2 on human ovarian tumour growth using a cell line derived from the ascites (i.e. free fluid in the peritoneal cavity) of a patient with serous cystadeno-carcinoma of the ovary. The tumour growth was inhibited dose-dependently in the range 10-100 ¡M by ginsenoside Rh2 and the DNA, RNA and protein syntheses of the tumour cells were likewise inhibited dose-dependently at above 15 ¡M of ginsenoside Rh2. Experiments on nude mice with transplanted human ovarian tumour cells demonstrated that combination therapy with cisplatin (a platinum-containing cytotoxic drug) and 10 ¡M ginsenoside Rh2 resulted in significant inhibition of tumour growth 31 days after inoculation and produced increased survival times when compared with untreated animals and those treated with either cisplatin or ginsenoside Rh2 alone. The effective synergistic combination yielded no adverse effects, thus suggesting clinical potential. A similar synergistic inhibition of the growth of cancer cells had been demonstrated in vitro earlier (Hwang et al., 1989) using a ginseng and vitamin C combination against cultured mouse leukaemia cells (L1210 and P388) and human rectal and colonic cancer cells.
Ginsenoside Rg3, also a diol-type saponin, was shewn to inhibit neoplasm metastasis and tumour cell infiltration in mice (Kitigawa et al., 1993) and inhibition of lung tumour metastasis also in mice was demonstrated using ginsenoside Rb2 and 20(R)- and 20(S)-ginsenosides Rg3 extracted from red ginseng (Mochizuki et al., 1995). These workers concluded that the mechanism of action was probably related to variations in cell adhesion and tumour cell invasion and antiangiogenetic activity. One year later Shinkai et al. (1996), using a cell monolayer invasion model, confirmed that ginsenoside Rg3 was a potent inhibitor of cell invasion by rat ascites hepatoma cells, melanoma cells, small lung carcinoma cells and human pancreatic adenocarcinoma cells. The structurally analogous ginsenoside Rb2, 20(R)-ginsenoside Rg2 and 20(S)-ginsenoside Rg3 demonstrated little inhibitory action and ginsenosides Rb1, Rc, Re, Rh1, 20(R)-Rh 1 and Rh2 were ineffectual. Ginsenoside Rg3 was also shewn to be an effective inhibitor of experimental pulmonary metastasis induced by highly metastatic mouse melanoma B16FE7 cells. Ginsenoside Rg3 was subsequently demonstrated as an inhibitor of intestinal adenocarcinomas. Iishi et al. (1997) used bombesin (gastrin releasing peptide) which significantly enhanced the occurrence of intestinal tumours and cancerous metastases in the peritoneum after 45 weeks. Rats were treated with subcutaneous injections of the carcinogenic azoxymethane (7.4 mg/kg body weight weekly) for 10 weeks, then subcutaneous injections of bombesin (40 ¡g/kg body weight on alternate days) and finally from week 20 subcutaneous injections of bombesin and ginsenoside Rg3 (2.5-5.0 mg/kg body weight) on alternate days until termination of the trial (week 45). Although ginsenoside Rg3 had little or no effect on the bombesin enhancement of intestinal tumours as it did not affect tumour growth or vascularity, it did significantly decrease cancer metastasis and thus the spread of cancer via peritoneal fluid.
Total ginsenosides (500 mg/day subcutaneously for 8 days) administered to mice implanted with S180 cancer cells reduced the rate of tumour bearing and the weight of individual tumours. Increase of natural killer cells, interferon and interleukin-2 produced by spleen cells suggests that ginsenosides play a positive role in the functioning of the natural killer cell-interferon-interleukin-2 regulatory network (Yu and Yang, 1987).
Investigating intermediate degradation products, prosapogenins and sapogenins prepared from Korean P. ginseng red ginseng saponins, Back et al. (1995) noted that cytotoxic activity varied against various cancer cell lines. Stereoisomerism did not appear to be significant although activity was inversely proportional to the number of sugar units linked to the sapogenin. Diol-type saponins, sapogenins and prosapogenins demonstrated higher cytotoxicity than the corresponding triol-types. In the same year Im et al. (1995) tested ginseng leaf saponins hydrolysed under alkaline conditions. The products obtained included monogluco-ginsenoside Rh1, monogluco-ginsenoside Rh2 and compound K (20-0-[^-D-glucopyranosyl]-20(S)-protopanaxadiol) and a mixture of the three demonstrated antitumour activity against human cancer cells.
Multidrug resistance is a problem in cancer chemotherapy. However Park et al. (1995c) reported the value of 20-(S)-ginsenoside Rg3, a red ginseng saponin, as an agent with a potent inhibitory effect on multidrug resistance in the treatment of human fibrocarcinoma resistant to the periwinkle alkaloid vincristine. Therefore ginseng can be used as a supporting treatment in chemotherapy strategies or radiotherapy.
Ginseng total saponins were successfully employed in the prevention of bone marrow haemopoietic stem cell destruction by harringtonine during the treatment of maurine L1210 leukaemia (Fan and Han, 1979). Aqueous extracts of ginseng are known to counter the side effects of the anticancer agents 5-fluorouracil and mitomycin C, decreasing the leucocyte count and reducing urine flow, renal plasma flow, glomerular filtration rate and urinary excretion of sodium (Kim and Kim, 1982), although Zhou and Han (1983) warned that the cytosine arabinoside-induced damage to bone marrow haematopoietic precursor cells in mice was increased by pretreatment with ginseng total saponins, orally or intraperitoneally. Therefore care is needed.
You et al. (1995) reported that intrahepatic sarcoma-180 tumour cells could be treated successfully in mice using the combination of radiotherapy and oral Panax ginseng extract. 0ral administration of P. ginseng root extract lengthened the survival time of tumour-bearing mice by 15.4 per cent and radiation treatment extended lifespan by 16.9 per cent but the combination of both treatments was much more effective increasing life by 82.9 per cent. Histopathological investigations revealed that the radiation treatment destroyed the cancer cells and also liver cells but the ginseng extract stimulated the recovery of the liver cells without infiltration of tumour cells. This agrees with the subsequent observations of Pande et al. (1998) who also noted that ginseng extract was non-toxic in mice at dose levels up to 1200 mg/kg. At 10-20 mg/kg doses the survival time of irradiated Swiss albino mice was considerably enhanced compared with untreated animals. In addition, radiation-induced damage to germ cells and loss of body weight were also reduced in pretreated mice. The radioprotective effect was attributed to increased levels of glutathione in the liver.
The chemically interesting polyacetylenic compounds isolated from both red and white ginseng roots proved to be equally fascinating pharmacologically. Kim et al. (1988b) noted that the compounds panaxydol (3-hydroxy-9S,10R-epoxyheptadeca-1-ene-4,6-diyne) and panaxynol (heptadeca-1,9-diene-4,6-diyne-3-ol) caused concentration-dependent haemolysis but panaxytriol (heptadeca-1-ene-4,6-diyne-3,9,10-triol) had no such effect. With liposomes comprising phosphatidyl-choline and phosphatidic acid, all three polyacetylenes suppressed osmotic behaviour to the same extent. However, with liposomes of phosphatidyl-choline, phosphatidic acid and cholesterol, panaxytriol produced the least suppression. Significantly it was observed that panaxydol caused nonspecific injury to L-1210 leukaemia cells by disrupting the cell membrane, nuclear envelope and mitochondria and it was concluded that the cytotoxicity of the polyacetylene compounds was due to the damaging effect on the cell membranes. Therefore panaxytriol, causing little damage to the cell membranes, was the least effective; this was due to its polarity and its minimal effect on the cholesterol of the lipid bilayers.
Polyacetylenic alcohols isolated from P. ginseng and P. pseudoginseng have been shewn to suppress tumour activity in vitro (Saita et al., 1994). Panaxynol, panaxydol and panaxytriol were studied with respect to in vitro cell growth. Water solubility varied but a-cyclodextrin complexes enabled solutions of active compounds to be formulated. The inhibitory effect of these compounds was much stronger against malignant cells than against normal cells: Inhibition was cytotoxic at high concentrations and cytostatic at low concentrations. Continuous contact between the compounds and the target cells is not apparently necessary and the mode of action is more concentration dependent than time dependent (Matsunaga et al., 1990). The action of panaxytriol was tumour-dependent and against B-16 melanoma the growth inhibition was definitely dose-dependent rather than time-dependent, panaxytriol being effective in mice at 40 mg/kg intramuscularly (Katano et al., 1990). Matsunaga et al. (1994) noted the antiproliferative activity of panaxytriol against several types of tumour cells and observed that panaxytriol and mitomycin C are synergistic against the human gastric carcinoma cell line (MK-1) or, if used singly, additive. The synergism was considered probably due to an acceleration of the mitomycin C effect on cellular accumulation prompted by the panaxytriol and also enhancement of mitomycin C accumulation in MK-1 cells caused by the decreased fluidity of the cell membranes in the presence of panaxytriol. Panaxynol, panaxydol and panaxytriol were also shewn to be cholesteryl ester transfer protein inhibitors in human subjects (Kwon et al., 1996).
Many polyacetylenic compounds have now been isolated from various Panax species and from tissue and callus cultures. Most are C14 and C17 compounds and the key structural unit appears to be hept-1-ene-4,6-diyne-3-ol. Thus panaxyne from P. ginseng roots is less effective against leukaemia L1210 cells because its structure is tetradeca-13-ene-1,3-diyne-6,7-diol and therefore lacks the key group (Kim et al., 1989d).
More research concerning the action and therapeutic application of polyacetylene compounds which have been isolated from both whole plant and callus extracts of various Panax species should concentrate on neoplasm inhibitors, leukaemia L1210 and sarcoma inhibitors and the use of 5-lipoxygenase inhibitors as allergy inhibitors.
Although saponins and polyacetylenes have been given anti-tumour roles in the overall action of ginseng, there is a further chemical group, the polysaccharides, which have also been cited as tumour inhibitors. Hatono et al. (1986) patented a purified polysaccharide preparation from the roots of P. notoginseng; the molecular weight was >100,000 and the product contained arabinose, galactose and glucose in the proportions 0.5:5.0:94.5. It was claimed as a tumor killing factor for use in cancer therapy. Other patented examples are cited in Chapter 9.
Explanation of the mechanism of action of such compounds on cancers has prompted many suggestions. The oral ingestion of ginseng polysaccharides prolonged the survival time of mice inoculated with S180 or Ehrlich tumour cells but did not affect Ehrlich cells in vitro. In tumour-bearing mice immunised with red sheep cells, oral administration of P. ginseng polysaccharides (400-800 |g/kg/day for 10 days) stimulated the production of plaque-forming cells, rosette-forming cells and antibodies by the spleen. In normal mice such immunological changes were not apparent. This suggests that the anti-tumour action of ginseng polysaccharides is linked to immunostimulation in the host animal (Qian et al., 1987).
Also, the ascites free fluid in the peritoneal cavity of sarcoma-180-bearing mice or hepatoma-bearing humans contains a lipolytic or fat-splitting factor, toxohormone-L. Lee et al. (1990b) discovered that an acidic polysaccharide from Korean red ginseng with a pectin-like a-1,4-polygalacturonan backbone and some acetoxyl groups significantly inhibited toxohormone-L-induced lipolysis at concentrations of 10 |/ml. It was also noted that the inhibitory effect of the main root of red ginseng was 2.3 times greater than that of white ginseng. The anticancer action is probably also related to hormone balance. It was reported (Zhu et al., 1991) that ginseng polysaccharides produced in mice splenocytes dose-dependent increases in the glycoproteins interleukin-2 and interferon and also in the natural killer cells. In animals bearing B16 melanoma tumours the levels of such compounds were lowered but could be reinstated by administration of ginseng polysaccharides (200, 100, 50 mg/kg/14 consecutive days intraperitoneally). This also supports the view that ginseng's anti-tumour action is related to its immunomodulatory action.
Lee et al. (1997) studied the purified lectin-free ginseng acidic polysaccharide ginsan, a compound with a molecular weight of about 150,000, isolated from P. ginseng. Ginsan stimulated the proliferation of B-cells and T-cells and the cytotoxicity of spleen cells to a wide range of tumour cells in vitro. The ginsan-
activated killer cells were produced in the presence of adherent macrophages and CD4+ cells; ginsan also activated macrophages to generate reactive nitrogenous intermediates and become tumouricidal. In addition, ginsan was effective in vivo versus B16 melanoma cell lines and in the benzo(a)pyrene-induced autochthonous lung tumour model. As ginsan appears to be relatively non-toxic having been injected at 1 g/kg body weight in mice without deaths, it is possibly a potential non-toxic antineoplastic immunostimulator activating several effector arms of the immune system. Subsequent work (Kim et al., 1998d) confirmed the inhibition of benzo(a)pyrene-induced autochthonous lung tumours in mice. Spleen cells became cytotoxic to a wide range of tumour cells after 5 days of culture with ginsan polysaccharide in a non-major histocompatability restricted manner. Seeking an explanation of the antineoplastic action it was reported that ginsan could generate lymphokine-activated killer (LAK) cells from both natural killer (NK) cells and T-cells through endogenously produced multiple cytokines; ginsan in association with rIL-2 synergistically developed LAK cells (2-15 fold). Ginsan was also shewn to inhibit pulmonary metastasis of B16-F10 melanoma cells and to intensify the suppression of lung colonies by rIL-2. Such properties suggest an immunopreventive and immunotherapeutic role for ginsan-type polysaccharides.
Inhibition of protein kinase C has been related to the suppression of tumours and Park et al. (1994a) reported that methanol and acetone protein extracts of ginseng as well as the ginsenosides Rb1, Rg1 and Rh2 inhibited protein kinase C. The methanol extract contained mainly glycopeptides with molecular weights below 18 Kda whilst the acetone fraction yielded mainly 18 Kda polypeptides.
As mentioned earlier, a Korean team (Kim et al., 1997) studied the long term effect of oral administration of P. ginseng extract recording the serum protein profile and immunoglobulin (Ig) isotype occurrence. Study of the occurrence of Ig isotypes including IgA, IgG1, IgG2a, IgG2b, IgG3 and IgM revealed a dose dependent decrease of serum IgG1 to 68 per cent of the control values when ginseng extract at 150 mg/kg daily was administered. Because the other Ig isotypes were not significantly affected it was suggested that, as the IgG1 isotype is rarely cytotoxic and can therefore act as a blocking antibody, the partial removal of the IgG1 isotype from the serum by ginseng action could permit more cytotoxic antibodies such as IgG2a to act thus preventing or inhibiting cancer growth.
A recent report by the Chinese group Chen et al. (1998) also stresses the efficacy of ginseng extracts as potent anti-tumour agents improving the cell immune system. Effective against croton oil-induced skin papillomas in mice at doses of 50-400 mg/kg, ginseng extracts can reduce the number and incidence and prolong the latent period of occurrence of such tumours; similarly the growth of transplantable mouse sarcoma S180 and melanoma B16 are inhibited. Weaker extracts (0.1 and 0.25 mg/ml) were shewn to possess antioxidant properties inhibiting Fe2+/cysteine-induced lipid peroxidation. Such results were obtained with extracts of red ginseng containing mixtures of ginsenosides, polyacetylenes, polysaccharides, etc. and laboratory animals were employed. Nevertheless the problem with ginseng is the lack of carefully designed clinical trials or clinical reports concerning successful prevention or treatment of cancers in man.
In the Korea Cancer Centre Hospital and General Hospital, Yun and Choi
(1995) undertook a comparative study of 1,987 pairs of patients. A "pair" consisted of one patient diagnosed with cancer and one without cancer and the object of the study was to compare the differences in each pair. The members of the "pair" were selected on the basis of sex, age and date of admission to the same hospital. Trained interviewers collated information on each patient's age, sex, marital status, history of ginseng use, socio-demographic status, education, lifelong occupational history, smoking habits and alcohol consumption. In addition data was collected concerning age of first use of ginseng, type of ginseng used, frequency of use and duration of treatments. After assessment of the results it was concluded that regular ingestion of Panax ginseng could reduce the risk of cancer by 50 per cent. For all types of cancer and all forms of ginseng the incidence of tumours decreased steadily with increasing duration of ginseng consumption. Patients who had taken ginseng for one year had 36 per cent less cancer incidence than non-users and those who had ingested ginseng for 5 or more years had 69 per cent less cancer incidence. It was also noted that those who had used ginseng treatment less than 50 times experienced a 45 per cent reduction but those who had used it more than 500 times had a 72 per cent reduction. The results indicated that ginseng was a more effective protection against cancers of the larynx, oesophagus, ovaries, pancreas and stomach but had no significant effect on bladder, breast, cervix and thyroid cancers. Further controlled trials are obviously necessary.
Some authors have stressed the antimutagenic properties of ginseng preparations using the mutagen mitomycin C as control. Ginsenosides from P. ginseng stems and leaves administered intraperitoneally or orally prevented the induction of micronuclei in murine bone marrow cells. When ginsenosides and mitomycin C were administered simultaneously the occurrence of micronuclei was much reduced. Such reduction was considered to be antimutagenic (Lu et al., 1991). The Russian group of Umnova et al. (1991) prepared bioginseng from ginseng callus cells by alcoholic extraction and lyophilisation and, using Chinese hamster cells, demonstrated that bioginseng could reduce the rate of spontaneous sister chromatid exchanges and the occurrence of mitomycin-C induced chromosome aberrations. Bioginseng also protected Ehrlich tumour cells against the mutagenic action of nitrosomethylurea. In a further communication these workers (Salikhova et al., 1994) confirmed the antimutagenic effect of bioginseng against nitrosomethylurea and cyclophosphamide treatment and suggested that the sister-chromatid exchange decrease was related to increased DNA repair induced by bioginseng. Zhu et al. (1994) also observed that the frequency of chromosome aberration induced by mitomycin-C in mice was significantly reduced in vivo in the presence of ginseng stem and leaf saponins and the best protection of genetic materials was obtained by treatment prior to mutagen application. Further work involving human subjects is essential.
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