Studies in humans
Supplemental amounts of a polysaccharide/oligosaccharide complex obtained from a Shiitake mushroom extract have been evaluated for the ability to lower the prostate-specific antigen level in patients (n=62) with prostate cancer. The data showed that the Shiitake mushroom extract alone was ineffective in the treatment of clinical prostate cancer (White et al., 2002). The efficacy and safety of Senseiro (containing extracts from Agaricus blazei Murill) and Rokkaku Reishi, (containing the Ganoderma lucidum mushroom) have been evaluated over 6 months in patients with prostate cancer in Japan (Yoshimura et al., 2010). Patients with biochemical failure after radical treatment for non-metastasized prostate cancer were enrolled in this open-label study. No partial response in terms of serum prostate-specific antigen was observed. Alteration of serum prostate-specific antigen doubling time did not correlate with that of serum testosterone levels. Serious adverse effects were not observed and no significant anticancer effects were observed with the intake of these two mushrooms in the study population.
In vitro studies (human cell lines)
The effects of Agaricus blazei Murill on the growth of human prostate cancer have been examined in vitro and in vivo. A. blazei, particularly in a broth fraction, inhibited cell proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines. The broth of A. blazei induced lactate dehydrogenase leakage in three cancer cell lines, whereas the activities of caspase 3 and the DNA fragmentation were enhanced the most in androgen-independent PC3 cells. Oral supplementation with the broth of A. blazei (with the higher ratio of beta-glucan) significantly suppressed tumour growth without inducing adverse effects in severe combined immunodeficient mice with PC3 tumor xenograft. The data suggested that the broth of A. blazei may directly inhibit the growth of prostate cancer cell via an apoptotic pathway and suppress prostate tumor growth via antiproliferative and antiangiogenic mechanisms (Yu et al., 2009a).
Beta-glucan, a polysaccharide, of the Grifola frondosa (Maitake) mushroom, has a cytotoxic effect, presumably through oxidative stress, on human androgen-independent prostatic cancer PC3 cells in vitro, leading to apoptosis (Fullerton et al., 2000). Another study in the same cell line showed similar cytotoxic effects from a water-soluble extract from Pleurotus ostreatus (Oyster), although the active components were not identified (Gu and Leonard, 2006).
Ganoderma lucidum has also been shown to inhibit proliferation in a dose- and time-dependent manner and induce apoptosis in human prostate cancer cells PC-3 (Jiang et al., 2004b). However, the molecular mechanisms responsible for the inhibitory effects of G. lucidum on these prostate cancer cells are still unclear. It has been found that G. lucidum inhibits the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells. These effects are caused by the inhibition of constitutively active AP-1 in prostate cancer cells, resulting in the down-regulation of secretion of Vascular Endothelial Growth Factor and Transforming Growth Factor beta (TGF-beta1) from PC-3 cells. The data suggest that G. lucidum inhibits prostate cancer-dependent angiogenesis by modulating MAPK (mitogen activated protein kinase) and Akt signaling and could have potential therapeutic use for the treatment of prostate cancer (Stanley et al., 2005). Interferon (IFN)-alpha2b has also been shown to have synergistic effects with mushroom extracts in inducing significant reductions reduction in PC-3 cell growth. This appears to be due to a synergistic potentiation leading to a G1 cell cycle arrest (Pyo et al., 2008).
Phellinus linteus has been reported to sensitise apoptosis induced by doxorubicin (an anti-cancer drug) in prostate cancer LNCaP cells suggesting that Phellinus linteus may have therapeutic potential to augment the magnitude of apoptosis induced by anti-prostate cancer drugs (Collins et al., 2006). Putrescine-1,4-dicinnamide from the gilled mushroom Pholiota spumosa (Basidiomycetes) has also been reported to inhibit cell growth of an androgen-independent human prostate cancer (PCA) cell line by inducing apoptosis, mediated, at least in part, by the activation of caspase cascades (Russo et al., 2007).
Animal model (mouse) studies
A Phellinus linteus extract has recently been reported to sensitize advanced prostate cancer cells to apoptosis in athymic nude mice (Tsuji et al., 2010). In this study, a xenograft assay, together with in vitro assays, were undertaken to evaluate the effect of Phellinus linteus on the genesis and progression of the tumours formed from the inoculation of prostate cancer PC3 or DU145 cells. Although Phellinus linteus treatment did not prevent the formation of the inoculated tumours, the growth rate of the tumors after Phellinus linteus treatment was significantly attenuated. Apoptosis occurred with the activation of caspase 3 in the tumours formed by inoculating prostate cancer DU145 or PC3 cells. The data were in agreement with data from cultured cells. The in vivo study suggested that Phellinus linteus attenuated tumour growth and caused tumour regression by inducing apoptosis.
Animal model (rat) studies
The inhibitory effects of methanol extracts of 19 edible and medicinal mushrooms on 5-alphareductase activity have been reported, with an extract of Ganoderma lucidum Fr. Krast (Ganodermataceae) showing the strongest 5-alpha-reductase inhibitory activity. The treatment of the fruit body of Ganoderma lucidum, or the extract prepared from it, significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. The results showed that Ganoderma lucidum might be a useful ingredient for the treatment of benign prostatic hyperplasia (Fujita et al., 2005).
Prostate weight increased significantly (37%) following treatment with a Phellinus linteus extract, and in particular, the stromal component of the prostate increased significantly by 80%. A suppression of transforming growth factor-beta1 expression by 56% was observed with the mushroom extract treatment. It was found that this mushroom extract enlarged the prostate and therefore administration of Phellinus linteus extract should be considered carefully by those with an enlarged prostate (Shibata et al., 2005).
Agaricus bisporus mushroom extract and one of its major components, conjugated linoleic acid (CLA) have been shown to decrease DU145 and PC3 prostate tumour size and tumour cell proliferation in nude mice treated with the mushroom extract, whereas tumour cell apoptosis was increased compared to pair-fed controls. Gene network analysis identified alterations in networks involved in cell death, growth and proliferation, lipid metabolism, the TCA cycle and immune response (Adams et al., 2008).