Initial Events of Ganoderma lucidum Related to the Bacillus calmette-guérin Efficacy and Toxicity on Pre-malignant and Malignant Uroepithelial Cell Lines

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 efficacy. In vitro and animal studies have demonstrated the anti-cancer
properties of a medicinal mushroom called Ganoderma lucidum (GL). In this study, a pre-malignant
human uroepithelial cell (HUC-PC) and malignant mouse bladder (MB49) cell models were utilized to
compare the effectiveness between ethanol extract of GL (GLe) and BCG on interleukin-6 (IL-6)
secretion and lactate dehydrogenase (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 in HUC-PC cells, suggesting the
potential synergism. GLe have also exhibited cytotoxic effects in both cell lines. During the initial four
hours of GLe exposure, 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 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 protective effects, and thus
reducing the BCG toxicity. These support the recently reported in vivo tumor inhibitory effects of GLe
exhibited in the MB49/C57 bladder cancer mice model.