Abstract 1462: Triterpene extract of <i>Ganoderma lucidum</i> inhibits proliferation of premalignant human prostate cells by regulation of epithelial mesenchymal transition
Authors: Yi Fang Lee, De-An Guo, Neil R. Thomas, Susan A. Watson
Journal: Cancer Research (2010)

Abstract Background: Prostate cancer is the leading cancer diagnosed in men. Ganoderma lucidum (GL), a well known medicinal fungus, has been widely used in the treatment and prevention of many diseases, including cancer, in Asian countries. The triterpene extract of GL, has been identified as an important active ingredient possessing anti-cancer activities, through, as yet an unknown mechanism of action. The aims of our current research were to characterise the inhibitory activity of triterpene extracts of GL in pre-malignant prostate cell lines (PINs) as a potential model of chemoprevention and to investigate the mechanism of action of triterpene. Materials and methods: Effects on growth of PIN cell lines were measured using an “in vitro” fluorometric cell viability assay and “in vivo” growth assays. Invasive behaviour of PIN was assessed “in vitro” by using a wound healing assay, and cell branching, in a matrigel invasion assay. The effect on angiogenesis was assessed by measuring formation of tubules by human endothelial cells. To identify the cellular targets of triterpene, two-dimensional gel electrophoresis was used, and proteins showing differential expression were identified by mass spectrometry. Effects on protein expression and gene regulation were further confirmed by western blotting, quantitative RT-PCR and luciferase reporter assay. Results: The triterpene extract of GL inhibited the “in vitro” proliferation of PINs with an IC50 ranging from 38.8μg/ml to 118.8μg/ml and inhibited the volume of PIN xenografts by 30% (p&amp;lt;0.05; 77mg/ml). In addition, triterpene (at the IC25) significantly suppressed angiogenesis (&amp;gt;95% inhibition, p&amp;lt;0.0001), migration (76% inhibition, p&amp;lt;0.001) and invasion of PIN (p&amp;lt;0.001). From proteomic analysis, two potential target proteins identified included the epithelial-mesenchymal transition (EMT) marker vimentin and the glycolytic enzyme enolase α. The down-regulation of vimentin and up-regulation of enolase α were further confirmed by western blotting. The possible role of triterpene in regulation of EMT markers including vimentin, E-cadherin, N-cadherin and slug was also demonstrated by quantitative RT-PCR of PIN cells collected from a cell branching assay. Additionally, triterpene was found to down-regulate the protooncogene c-myc, a downstream target of enolase α, which plays an important role in the cell cycle, cell proliferation and apoptosis. Conclusion: These findings suggest that the triterpene extract of GL could be a promising new agent in prevention of prostate cancer by regulation of EMT and c-myc. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1462.