Abstract 5487: Anti-proliferative, apoptotic and immunological effects of ganoderic acid DM on prostate cancer cells

Abstract

Abstract Natural extracts have been the focus of recent investigation in the design of novel chemotherapeutics. One potential natural therapeutic agent is ganoderic acid DM (GA-DM), an extract from the Ganoderma lucidum mushroom previously shown to inhibit 5-α-reductase activity and prevent binding of dihydrotestosterone to the androgen receptor in prostate cancer cells. Studies in our laboratory used nonradioactive cell proliferation and cytotoxicity assays to investigate GA-DM's effect on both androgen dependent and independent prostate cancer cell lines, revealing dose dependent killing and inhibition of proliferation by this natural extract. Microscopic analysis using Hoechst staining showed DNA breakdown consisted with apoptosis in GA-DM-treated prostate cancer cells. Annexin V staining confirmed low levels of apoptotic cell death when treated with GA-DM. Western blotting and biochemical analysis revealed that GA-DM induced apoptotic cell death that was independent of caspase activation, cytochrome c release, and Bax induction. Further investigation showed that GA-DM treatment activated HLA protein expression, implying some immunological involvement contributing to GA-DM-induced cell death. This study outlines a novel mechanism of GA-DM-induced inhibition of proliferation, induction of apoptosis and immune components in both androgen dependent and independent prostate cancer cells, the implications of which support GA-DM's potential use in multimodal chemoimmunotherapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5487. doi:10.1158/1538-7445.AM2011-5487