Methylseleninic acid elevates REDD1 and inhibits prostate cancer cell growth despite AKT activation and mTOR dysregulation in hypoxia

Indu Sinha, Joshua E. Allen, John T. Pinto, Raghu Sinha

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Methylseleninic acid (MSeA) is a monomethylated selenium metabolite theoretically derived from subsequent β-lyase or transamination reactions of dietary Se-methylselenocysteine that has potent antitumor activity by inhibiting cell proliferation of several cancers. Our previous studies showed that MSeA promotes apoptosis in invasive prostate cancer cells in part by downregulating hypoxia-inducible factor HIF-1α. We have now extended these studies to evaluate the impact of MSeA on REDD1 (an mTOR inhibitor) in inducing cell death of invasive prostate cancer cells in hypoxia. In both PTEN+ and PTEN- prostate cancer cells we show that MSeA elevates REDD1 and phosphorylation of AKT along with p70S6K in hypoxia. Furthermore, REDD1 induction by MSeA is independent of AKT and the mTOR inhibition in prostate cancer cells causes partial resistance to MSeA-induced growth reduction in hypoxia. Our data suggest that MSeA induces REDD1 and inhibits prostate cancer cell growth in hypoxia despite activation of AKT and dysregulation of mTOR.

Original languageEnglish (US)
Pages (from-to)252-264
Number of pages13
JournalCancer medicine
Volume3
Issue number2
DOIs
StatePublished - Apr 1 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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