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.

Author(s) Details

 Dr. John Wai-Man Yuen
School of Nursing, The Hong Kong Polytechnic University, Hong Kong, China.

Prof. Mayur-Danny I. Gohel
Department of Medical Science, Tung Wah College, Hong Kong, China.

Chi-Fai Ng
SH HO Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.

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