Androgen receptor-dependent and -independent mechanisms mediate Ganoderma lucidum activities in LNCaP prostate cancer cells

Androgen receptor-dependent and -independent mechanisms mediate Ganoderma lucidum activities in LNCaP prostate cancer cells.

Ganoderma lucidum (Curt.:Fr.) P. Karst, a medicinal fungus, has been widely used in Asian countries for centuries to prevent or treat a variety of diseases, including cancer. However, the mechanisms responsible for the effects of G. lucidum on cancer cells remain to be elucidated. We have previously shown that ethyl acetate extract of G. lucidum inhibits LNCaP prostate cancer cell viability and proliferation. We also demonstrated that G. lucidum extract decreased androgen receptor transcriptional activity, suppressed levels of secreted prostate-specific antigen, and suppressed androgen receptor protein level. In this study we investigated the mechanisms that underlie the activities of G. lucidum crude extract and its active fraction GLF4 in LNCaP prostate cancer cells. Our data demonstrate that G. lucidum inhibits cell viability by induction of apoptosis through the extrinsic pathway that include activation of caspase-8 and caspase-3 and inhibits cell proliferation by the down-regulation of cyclin D1 expression. Furthermore, G. lucidum crude extract and fraction GLF4 interfere with androgen receptor function via competition with the natural ligand dihydrotestosterone and suppression of androgen receptor/androgen response element complex formation. These results indicate that G. lucidum extracts have profound activity against LNCaP cells that merits further investigation as a potential therapeutic agent for the treatment of prostate cancer.

The culinary-medicinal mushroom Coprinus comatus as a natural antiandrogenic modulator.

Prostate cancer is the most common cancer diagnosed in men. Chemotherapy, androgen ablation, and androgen antagonist treatments have proven to have significant effects in the early stages of prostate cancer, whereas advanced prostate cancer is resilient to such treatments. The androgen receptor (AR), a ligand-dependent transcription factor, is the major drug target of prostate cancer therapy. Transition to the androgen-independent stage involves the activation of signaling pathways, AR gene mutations, and other mechanisms. Higher basidiomycetes mushrooms have been used since ancient times in folk medicine to treat a diversity of diseases, including cancer. The present study evaluates the antiandrogenic activity of different Coprinus comatus strains in their ability to interfere with AR function. The authors found that the most active extract was C comatus strain 734 extracted with hexane (CC734-H). This extract was able to (1) inhibit AR-mediated reporter activity, (2) inhibit the proliferation and viability of the LNCaP cell line, and (3) inhibit the colony formation of the LNCaP cell line, in comparison to the DU-145, PC-3, and MDA-Kb2 cells. In addition, CC734-H was able to reduce AR levels and prostate-specific antigen gene expression in the LNCaP-treated cell line. This study illustrates the potential of the C comatus mushroom as a natural antiandrogenic modulator that could serve in the treatment of prostatic diseases.