Antitumor Effects of Ganoderma lucidum

摘要

Ganoderma lucidum is a natural product with antitumor activity. The hot water extracts of the mycelium of G. lucidum (GLP) exhibited antitumor effect against fibrosarcoma in C<,3>H mice and inhibited the metastasis of the tumor to the lung. We developed a procedure to fractionate GLP into polysaccharide fraction GLP (AI) and non-polysaccharide fraction. We found that GLP (AI) is the major component to show the in vivo antitumor effect on fibrosarcoma growth in C<,3>H mice. The effects of GLP (AI) on cytotoxic activity of splenic natural killer cells (NK) were assessed in normal mice and in tumor-bearing mice. The antitumor effect was observed in mice by either intravenous, intraperitoneal or oral administrations of GLP (AI) produced a dose-related increase in the splenic NK activity in different mouse strains. In addition, GLP (AI) produced an increase in the titer of serum interferon (IFN). Furthermore, the decreased splenic NK cytotoxicity of tumor-bearing mice was restored by GLP (AI) treatment. The GLP (AI) was found to induce differentiation of leukemic U937 cells. The PS-G, which was purified from GLP (AI) by Sephadex G-50 and ion exchange column chromatographies contained the active principle to induce differentiation of leukemic U937 cells. It could stimulate blood mononuclear cells to secrete cytokines, which were both anti-proliferative and differentiation inductive to the leukemic U937 cells. On the other hand, we utilized an in vitro culture system to analyze the effects of the PS-G on the functions of macrophages and T lymphocytes, and on the growth of leukemic cells. The results showed that cytokine production by either macrophages or T lymphocytes was greatly increased after treatment with PS-G. The proliferation of leukemic cells was not affected' by PS-G alone; but was significantly inhibited by the conditioned medium from PS-G activated blood mononuclear cells (PSG-MNC-CM). Antibody neutralization studies revealed that the anti-tumor activity of PSG-MNC-CM was derived mainly from the elevated cytokines, especially TNF-α and IFN- γ. These cytokines induced apoptosis and differentiation in the PS- G treated leukemic cells. Furthermore, antitumor activity of G. lucidum on intraperitoneally implanted Lewis lung carcinoma in syngeneic C57BL/6 mice was investigated. The results showed that GLP signifi-cantly increased the life-span of tumor-implanted mice, when administered intraperitoneally alone or in combination with cytotoxic antitumor drugs or a synthetic immunomodulator. The GLP was not cytotoxic to cultured cells and the antitumor activity was abolished by pretreatment of mice with cyclosporine. Taken together, the aforementioned observations suggest that GLP exerts its antitumor effect mainly through immunopotentiation of the tumor-bearing animals.