Telomerase-Associated Apoptotic Events by Mushroom Ganoderma lucidum on Premalignant Human Urothelial Cells

Abstract

The chemopreventive effects of Ganoderma lucidum was tested, using a tumorigenic transformable human urothelial cell (HUC-PC) model. These in vitro data show that G. lucidum can inhibit the viability and growth of HUC-PC. This could be explained by a concomitant induction of apoptosis and inhibition of telomerase activity. Significant exteriorization of phosphatidylserine was detected by Annexin-V on cell surface, and the cells subsequently lost membrane integrity for uptake of 7-amino-actinomycin D dye. Additionally, the levels of hydrogen peroxide and 8-hydroxy-2′-deoxyguanosine (8-OHdG) production of the apoptotic cells were significantly increased. The induction of apoptosis and suppression of telomerase activity help to explain the anti-HUC-PC growth properties; however, the induction of oxidative stress requires further study. This study strongly suggests that G. lucidum is a potential source of chemopreventive agents for bladder cancer based on its effectiveness in controlling the premalignant urothelial cell growth and carcinogen-induced transformation.

ACKNOWLEDGMENTS

The authors acknowledge the Research Committee of the Hong Kong Polytechnic University for the postgraduate scholarship (RGH8) and Sir Edward Youde Memorial Fellowship awarded to John Yuen to conduct this study. The authors are grateful to Dr. J. Y. Rao (University of California, Los Angeles, Medical Center) for providing the SV40-HUC-PC cell line and professional advices. The authors specially thank Mike Chiu (Hong Kong Polytechnic University) and research staff of City University of Hong Kong, Helen Mok, and Wai Yu for technical assistances. This study was partially supported by a grant from City University of Hong Kong (7002117) to Dr. Au. We also thank Dr. Maureen Boost for critical reading of the manuscript.