Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Citations Over TimeTop 20% of 2011 papers

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.

Related Papers

• → ERBB2 Increases Metastatic Potentials Specifically in Androgen-Insensitive Prostate Cancer Cells(2014)23 cited
• → Metadherin is an apoptotic modulator in prostate cancer through miR-342-3p regulation(2018)11 cited
• → Invasive Cx43high sub-line of human prostate DU145 cells displays increased nanomechanical deformability(2017)5 cited
• → Methylation dependent miR-510 in prostate cancer: A novel upcoming candidate for prostate cancer(2016)4 cited
• Expression of survivin in prostate cancer cell lines(2007)