These poly-saccharides are of different chemical composition, with most belonging to the group of β-glucans; these have β-(1→3) linkages in the main chain of the glucan and additional β-(1→6) branch points that are needed for their anti-tumor action. High molecular weight glucans appear to be more effective than those of low molecular weight. Chemical modification is often carried out to im-prove the anti-tumor activity of polysaccharides and their clinical qualities (mostly water solubility).
• prevention of oncogenesis by oral consumption of mushrooms or their preparations;
• direct antitumor activity against various allogeneic and syngeneic tumors;
• immune-potentiating activity against tumors in combination with chemotherapy;
• preventive effect on tumor metastasis.
A good example of preventive effect is given by Japanese research on their popular edible and medicinal mushroom, Hypsizygus marmoreus (Ikekawa 2001). Control mice were bred on an ordinary diet and treated mice with a diet containing 5% dried fruit body of H. marmoreus. All mice were i.p. injected with a strong carcinogen, methyl-cholanthrene, and carcinogenesis of the mice was investigated. At the end of the 76-week observation, 21 of the 36 control mice developed tumors, but only 3 of 36 mice in the treated group had tumors. The authors concluded that the mechanism of cancer-inhibitory and cancer-preventing activities of edible mushrooms was due to immunepotentiation (Ikekawa 2001).
Researchers demonstrated that the cancer death rate of farmers whose main occupation was producing Flammulina velutipes (a well known medicinal mush-room in Japan) was remarkably lower than that of the general population in the Prefecture (Ikekawa 1995, 2001). Another similar observation in Brazil brought about extensive studies – and popularity – of Agaricus blazei (see below).
Mushroom polysaccharides exert their antitumor action mostly via activation of the immune response of the host organism. These substances are regarded as biological response modifiers (BRMs; Wasser and Weis 1999). This basically means that:
- they cause no harm and place no additional stress on the body;
- they help the body to adapt to various environmental and biological stress-es;
- they exert a nonspecific action on the body, supporting some or all of the major systems, including nervous, hormonal, and immune systems, as well as reg-ulatory functions (Brekhman 1980).
The immunomodulating action of mushroom polysaccharides is especially valuable as a prophylactic, a mild and non-invasive form of treatment, and in the prevention of metastatic tumors, etc.
Polysaccharides from mushrooms do not attack cancer cells directly, but produce their anti-tumor effects by activating different immune responses in the host. This has been verified in many experiments, such as the loss of the anti-tumor effect of polysaccharides in neonatal thymectomized mice or after administration of anti-lymphocyte serum (Ooi and Liu 1999). Such results suggest that the anti-tumor action of polysaccharides requires an intact T-cell component and that the activity is mediated through a thymus-dependent immune mechanism. Also, the anti-tumor activity of lentinan and other polysaccharides is inhibited by pretreatment with anti-macrophage agents (such as carrageenan).
Mushroom-derived glucan and polysaccharopeptides can act as immunemodulators. The ability of these compounds to enhance or suppress immune responses can depend on a number of factors including dosage, route of administration, timing and frequency of administration, mechanism of action or the site of activity.
Several mushroom compounds have been shown to potentate the host’s innate (non-specific) and acquired (specific) immune responses and activate many kinds of immune cells that are important for the maintenance of homeostasis, e.g. host cells (such as cytotoxic macrophages, monocytes, neutrophils, natural killer cells, dendritic cells) and chemical messengers (cytokines such as interleukins, interferon, colony stimulating factors) that trigger complement and acute phase responses. They can also be considered as multi-cytokine inducers able to induce gene expression of various immunemodulatory cytokines and cytokine receptors. Lymphocytes governing antibody production (β-cells) and cell-mediated cytotoxicity (T-cells) are also stimulated.
Cancer Research UK state ‘Human epidemiological studies in Japan and Brazil strongly suggest that regular consumption of certain medicinal mushrooms over prolonged periods of time significantly reduce the levels of cancer incidence’. And, ‘There is increasing evidence with experimental animals that regular feeding of powered medicinal mushrooms can have a cancer preventative effect, demonstrating both high anti tumor activity and restriction of tumor metastasis’. Medicinal mushroom extracts can be used to improve quality of life by alleviating the side effects of radio and chemotherapy such as fatigue, reduced appetite, bone marrow suppression and the risk of opportunistic infection.
Cancer Research UK state, ‘These compounds have been shown to be safe when taken over long periods of treatment and significantly, these compounds appear to reduce the adverse effects of radiotherapy and chemotherapy. These results are in marked contrast to the well documented adverse side effects associated with most chemo therapeutic compounds and also to a lesser extent, certain immune therapeutics that have been shown to be capable of causing fevers, chills, rash, oedema, arthralgia, hypotension, congestive heart failure or CNS toxicities’. Many compounds from medicinal mushrooms have been classified as anti-tumour agents by the US National Cancer Institute.