Chemical and Biochemical Basis of the Anti-tumor Properties of Ganoderma lucidum

摘要

The fruiting bodies of Ganoderma lucidum are edible, medicinal mushrooms known as Ling Zhi in China. Ling Zhi has been used in traditional Chinese medicine (TCM) for over 2000 years with a reputation rivaling that of ginseng. In addition to the fruiting bodies, the spores and cultivated mycelia have recently been used as health foods and herbal medicines. As a superior herbal medicine, it has been used in TCM for promotion of vitality and longevity. In modern Chinese medicine, Ganoderma lucidum is used in the treatment of debility and weakness, hepatitis, diabetes, altitude sickness, cardiovascular diseases, AIDS and cancer. Scientific studies on extracts and substances from Ganoderma lucidum have demonstrated their anti-aging, cardiovascular, hepato-protective, hypoglycemic, immuno-modulatory, anti-viral and anti- tumor effects. This evidence provides a pharmacological basis for their ancient and contemporary medical applications. Chemical investigations on the fruiting bodies, spores and mycelia of Ganoderma lucidum have shown that these mushrooms contain various bioactive substances. Active constituents of Ganoderma lucidum include polysaccharides, proteins, nucleosides, fatty acids, terpenoids and sterols. Water or alcohol extracts have been used for investigation of its biological activities. Water extract contains biological compounds that are responsible for its immunological and anti-inflammatory properties. In contrast, alcohol extract contains biological compounds that lower blood cholesterol levels, blood glucose levels, and platelet aggregation. While the anti-tumor effects can be attributed both to the water soluble polysaccharide and alcohol soluble triterpenes. Recent clinical and pharmacological research substantiating the benefits and effects of Ganoderma lucidum has focused on tumor activities. This presentation .attempts to review and analyze our current knowledge on the anti-tumor properties and mechanism of Ganoderma lucidum extracts. Some terpenoids and their derivatives isolated from Ganoderma lucidum are cytotoxic and have antitumor activities. Over one hundred different triterpenoids have been found in fruiting bodies, spores and mycelia of Ganoderma lucidum. These include highly oxidized lanostanoid-type triterpenes, such as ganoderic acids, ganoderenic acids, ganolucidic acids, lucidenic acids, ganoderiol type 1 and type 2, ganoderals, lucidones, furnaoganoderic acid and other terpenoid components. Some of these compounds are known for their anti-proliferative properties investigated in various cancer cell lines. Recent research has been expanded into their antiangiogenesis and apoptotic properties. The water extracts of Ganderma lucidum were reported to have immuno-modulatory and anti-tumor activities in many animal studies. Different anti-tumor polysaccharides and protein bound polysaccharides including β-D-glucan, glucuronoglucan, xycoglucan, mannoglucan and their protein complexes have been fractionated and purified. The water-soluble anti-tumor substances are ganoderan, GL-A, GL-B, GL-C, GLB-7 and β-immunan. Recently, a fucose-containing glycoprotein fraction with immuno-modulatory and anti-tumor activities has been identified from the water extract of Ganoderma lucidum. Functional and proteomics analyses indicate that a fucose-containing polysaccharide fraction is responsible for stimulating the expression of tumoricide cytokines. Mechanistic studies on the anti-tumor activities of β-D-glucan and GL-B have indicated their anti-tumor activities to be accomplished by enhancing host mediated mechanisms including increased IL-2 production and stimulation of cytotoxic T lymphocytes and NK activity. The hypothesis that some of the active constituents of Ganoderma lucidum may be able to skew the immune system away from the Th2 state into the Th1 state to benefit the tumor-bearing host will be discussed.