Abstract
Alternative strategies are needed to control growth of advanced and hormone refractory prostate cancer. In this regard, we investigated the efficacy of methylseleninic acid (MSeA), a penultimate precursor to the highly reactive selenium metabolite, methylselenol, to inhibit growth of invasive and hormone refractory rat (PAIII) and human (PC-3 and PC-3M) prostate cancer cells. Our results demonstrate that MSeA inhibits PAIII cell growth in vitro as well as reduces weights of tumors generated by PAIII cells treated ex vivo. A significant reduction in the number of metastatic lung foci by MSeA treatment was also noted in Lobund-Wistar rats. The PAIII cells along with PC-3, DU145 and PC-3M cells undergo apoptosis after MSeA treatments in both normoxia and hypoxia. Treatment of metastatic rat and human prostate cancer cell lines with MSeA decreased hypoxia-inducible factor-1α (HIF-1α) levels in a dose-dependent manner. Additionally, HIF-1α transcription activity both in normoxic and hypoxic conditions is reduced after MSeA treatment of prostate cancer cells. Furthermore, VEGF and GLUT1, downstream targets of HIF-1α, were also reduced in prostate cancer cells after MSeA treatment. Our study illustrates the efficacy of MSeA in controlling growth of hormone refractory prostate cancer by downregulating HIF-1α, which is possibly occurring through stabilization or increase in prolyl hydroxylase activity.
Original language | English (US) |
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Pages (from-to) | 1430-1439 |
Number of pages | 10 |
Journal | International Journal of Cancer |
Volume | 130 |
Issue number | 6 |
DOIs | |
State | Published - Mar 15 2012 |
Keywords
- HIF-1α
- hormone refractory prostate cancer
- methylseleninic acid