Androgens regulate TRAIL-induced cell death in prostate cancer cells via multiple mechanisms

Diping Wang, Ji Lu, Donald J. Tindall

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising therapeutic agent for prostate cancer because it selectively induces apoptosis in cancer cells but not in normal cells. Previous reports have suggested that androgens regulate TRAIL-induced apoptosis in prostate cancer cells. However, there are discrepancies between these reports of how androgens affect TRAIL-induced cell death. To clarify the role of androgens on TRAIL-induced apoptosis in prostate cancer cells, we investigated the effects of androgen on TRAIL-induced cell death in a dose-response manner. Our results showed that although androgens sensitize LNCaP cells to TRAIL-induced apoptosis, this effect is dose-dependent and biphasic. We found that low levels of androgen are superior to high levels of androgen in term of sensitizing LNCaP cells to TRAIL. We also found that upregulation of DR5 (TRAIL-R2) expression by androgens is critical for sensitizing LNCaP cells to TRAIL. However, low levels of androgen are sufficient to induce DR5 expression and sensitize LNCaP cells to TRAIL-induced cell death. High levels of androgen alter the TRADD/RIP1 ratio, which may contribute to NF-κB activation and sequentially inhibit TRAIL-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)136-144
Number of pages9
JournalCancer Letters
Volume335
Issue number1
DOIs
StatePublished - Jul 10 2013

Keywords

  • Androgen
  • Appoptosis
  • Prostate cancer
  • TRADD
  • TRAIL

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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