Abstract B117: Methylseleninic acid inhibits HIF-1α in hormone refractory prostate cancer cells in vitro

Abstract

Abstract B117 There is a need to prevent the recurrence of the residual hormone refractory prostate cancer following a radical prostectomy. Till date, the approaches to effectively control the recurrence are not successful. To use an alternative strategy, we investigated the efficacy of methylseleninic acid (MSeA), a potent selenium compound, to inhibit growth of hormone refractory prostate adenocarcinoma (PAIII) cells. These PAIII cells were derived from a metastatic prostate tumor produced spontaneously in a Lobund-Wistar (LW) rat. Our results demonstrate that MSeA inhibits PAIII cell growth in vitro as measured by MTT assay and it induces apoptosis in these cells in a dose-dependent manner as evidenced by PARP-cleavage. Additionally, markers of survival and proliferation (p-AKT, PCNA) are reduced in PAIII cells in a dose-dependent treatment by MSeA. One of the key factors involved in progression of androgen independent prostate cancers, Aurora-B kinase is decreased in MSeA-treated PAIII cells. Hypoxia is a key regulatory factor in prostate cancer and compromised oxygenation of tumor tissue plays a role in the aggressive nature of PAIII tumors in LW rats. In MSeA-treated PAIII cells, the nuclear hypoxia inducible factor (HIF-1α) levels are decreased in a dose-dependent manner. We have further verified reduction in weights of subcutaneous tumors produced by PAIII cells pre-treated with MSeA in LW rats. The current study illustrates the efficacy of MSeA in controlling growth of hormone refractory prostate cancer in vitro. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B117.