The effects of Ganoderma lucidum on initial events related to the Bacillus Calmette-Guérin efficacy and toxicity on high-risk uroepithelial cells : an in vitro preliminary study

A novel prophylactic regimen is demanded for preventing bladder cancer recurrence, because of the high side-effect tolls of conventional adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy, in addition to its only moderate effi- cacy. In vitro and animal studies have demonstrated the anti-cancer properties of a medicinal mushroom called Gano- derma lucidum (GL). In this study, a pre-malignant human uroepithelial cells (HUC-PC) model was utilized to compare the effectiveness between ethanol extract of GL (GLe) and BCG on interleukin-6 (IL-6) secretion and lactate dehydro- genase (LDH) cytotoxicity. Additionally, parameters relevant to the BCG efficacy and safety, including free soluble fibronectin (FN) and cell-surface glycosaminoglycans (GAGs) levels were tested, following the exposure of GLe to the cells. GLe at 100 μg/ml and BCG at 4.8 × 10⁷ CFU were shown to induce equivalent levels of IL-6, suggesting the po- tential synergism, while the tested concentrations of GLe were non-cytotoxic. During the initial four hours of GLe ex- posure, the free FN concentrations in harvested media were significantly reduced that might facilitate the binding of BCG for uroepithelial internalization to enhance BCG efficacy. Furthermore, the cell membrane-bound GAGs levels of HUC-PC cells were significant increased in response to GLe to suggest cellular protection from BCG infection. In summary, current findings suggest the potential additive synergism of GLe with the BCG efficacy, as well as its protec- tive effects, and thus reducing the BCG toxicity.