Resveratrol induces sumoylated COX-2-dependent anti-proliferation in human prostate cancer LNCaP cells

Tsai Mu Cheng, Yu Tang Chin, Yih Ho, Yi Ru Chen, Yung Ning Yang, Yu Chen Yang, Ya Jang Shih, Ting I. Lin, Hung Yun Lin, Paul J. Davis

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12 Citations (Scopus)

Abstract

Cyclooxygenase (COX)-2 has been implicated in cancer development. However, resveratrol-induced nuclear accumulation of COX-2 enhances p53-dependent anti-proliferation in different types of cancers. Treatment with resveratrol leads to phosphorylation and nuclear translocation of mitogen-activated protein kinase (ERK1/2), and accumulation of nuclear COX-2 to complex with pERK1/2 and p53. The consequence is Ser-15 phosphorylation of p53 (pSer15-p53), and induction of anti-proliferation in cancer cells. We investigated the mechanisms by which resveratrol-inducible COX-2 facilitates p53-dependent anti-proliferation in prostate cancer LNCaP cells. Resveratrol treatment caused nuclear accumulation and complexing of ERK1/2, pSer15-p53 and COX-2 which was activated ERK1/2-dependent. Knockdown of SUMO-1 by shRNA also reduced nuclear accumulation of COX-2. Inhibition of nuclear accumulation by the COX-2 specific inhibitor, NS-398, inhibited co-localization of nuclear COX-2 and SUMO-1. Similar results were observed in the PD98059-treated cells. Finally, inhibition of SUMO-1 expression also reduced resveratrol-induced expression of pro-apoptotic genes but increased the expression of proliferative genes. In summary, these results demonstrate that inducible COX-2 associates with phosphorylated ERK1/2 to induce the phosphorylation of Ser-15 in p53 and then complexes with p53 and SUMO-1 which binds to p53-responsive pro-apoptotic genes to enhance their expression. The inhibition of COX-2 expression and activity significantly blocks the pro-apoptotic effect of resveratrol.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalFood and Chemical Toxicology
Volume112
DOIs
Publication statusPublished - Feb 1 2018

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Keywords

  • Inducible COX-2
  • p53 and anti-proliferation
  • Resveratrol
  • Sumoylation

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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