Pharmacological values of medicinal mushrooms for prostate cancer therapy: the case of Ganoderma lucidum.

Prostate cancer (PCa) is the most common male malignancy in many Western countries. Primary PCa is hormone dependent and is manageable by hormonal therapy. However, it rapidly develops to hormone-refractory tumors due to the accumulation of mutations in the androgen receptor and/or the acquisition of alternative cellular pathways that support proliferation and inhibit apoptosis of prostate cancer. To date, no effective therapy is available for clinically hormone-insensitive or hormone-refractory stages of prostate cancer.

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.

Medicinal mushroom modulators of molecular targets as cancer therapeutics.

Empirical approaches to discover anticancer drugs and cancer treatments have made limited progress in the past several decades in finding a cure for cancer. The expanded knowledge of the molecular basis of tumorigenesis and metastasis, together with the inherently vast structural diversity of natural compounds found in mushrooms, provided unique opportunities for discovering new drugs that rationally target the abnormal molecular and biochemical signals leading to cancer. This review focuses on mushroom low-molecular-weight secondary metabolites targeting processes such as apoptosis, angiogenesis, metastasis, cell cycle regulation, and signal transduction cascades. Also discussed in this review are high-molecular-weight polysaccharides or polysaccharide-protein complexes from mushrooms that appear to enhance innate and cell-mediated immune responses, exhibit antitumor activities in animals and humans, and demonstrate the anticancer properties of selenium compounds accumulated in mushrooms.