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In this study, we investigated the effects of Ganoderma lucidum (Reishi) on cell proliferation, the cell cycle, and apoptosis in human prostate cancer cells PC-3. Ganoderma lucidum, an oriental medical mushroom, has been widely used in Asian countries for centuries to prevent or treat different diseases, including arthritis, bronchitis, gastric ulcer, hepatitis, hepatopathy, hypertension, inflammation, nephritis, and cancers. However, the mechanism(s) responsible for the effects of Ganoderma lucidum on cancer cells remain to be elucidated. We have previously demonstrated that Ganoderma lucidum suppressed the migration of highly invasive human breast and prostate cancer cells by inhibiting transcription factors NF-κB and AP-1, resulting in the down-regulation of the expression of urokinase plasminogen activator (uPA) and uPA receptor (uPAR). Here we determined the effects of Ganoderma lucidum on cell proliferation, the cell cycle, apoptosis, and the expression of cell cycle-regulating and apoptotic proteins in PC-3 cells. Our results demonstrated that Ganoderma lucidum inhibits cell proliferation in a dose- and time-dependent manner by cell cycle arrest at G2/M phase, down-regulates the expression of cyclin B and Cdc2, and up-regulates p21 expression. Although Ganoderma lucidum did not influence G1/G0 phase of the cell cycle, a slight decrease in the expression of NF-κB-regulated cyclin D1 was observed. Furthermore, Ganoderma lucidum induced apoptosis of PC-3 cells with a moderate decrease in the expression of NF-κB-regulated Bcl-2 and Bcl-xl and markedly increased the expression of proapoptotic Bax protein, resulting in the enhancement of the ratio of Bax/Bcl-2 and Bax/Bcl-xl to apoptosis. These results suggest that Ganoderma lucidum inhibits cell proliferation and induces apoptosis by NF-κB-dependent as well as NF-κB-independent mechanisms. In conclusion, our data demonstrate that Ganoderma lucidum inhibited the growth of human prostate cancer cells by cell cycle arrest at G2/M phase and induced apoptosis. These findings suggest that Ganoderma lucidum exerts its effect on cancer cells by multiple mechanisms and may have potential therapeutic use for the prevention and/or treatment of human prostate cancer.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]