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

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)67-75
頁數9
期刊Food and Chemical Toxicology
112
DOIs
出版狀態已發佈 - 二月 1 2018

指紋

resveratrol
prostatic neoplasms
prostaglandin synthase
Cyclooxygenase 2
Prostatic Neoplasms
Phosphorylation
phosphorylation
Genes
Cells
neoplasm cells
Neoplasms
Cyclooxygenase 2 Inhibitors
Mitogen-Activated Protein Kinase 1
neoplasms
genes
Small Interfering RNA
Mitogen-Activated Protein Kinases
mitogen-activated protein kinase
Gene Expression

ASJC Scopus subject areas

  • Food Science
  • Toxicology

引用此文

Resveratrol induces sumoylated COX-2-dependent anti-proliferation in human prostate cancer LNCaP cells. / Cheng, Tsai Mu; Chin, Yu Tang; Ho, Yih; Chen, Yi Ru; Yang, Yung Ning; Yang, Yu Chen; Shih, Ya Jang; Lin, Ting I.; Lin, Hung Yun; Davis, Paul J.

於: Food and Chemical Toxicology, 卷 112, 01.02.2018, p. 67-75.

研究成果: 雜誌貢獻文章

Cheng, Tsai Mu ; Chin, Yu Tang ; Ho, Yih ; Chen, Yi Ru ; Yang, Yung Ning ; Yang, Yu Chen ; Shih, Ya Jang ; Lin, Ting I. ; Lin, Hung Yun ; Davis, Paul J. / Resveratrol induces sumoylated COX-2-dependent anti-proliferation in human prostate cancer LNCaP cells. 於: Food and Chemical Toxicology. 2018 ; 卷 112. 頁 67-75.
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title = "Resveratrol induces sumoylated COX-2-dependent anti-proliferation in human prostate cancer LNCaP cells",
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.",
keywords = "Inducible COX-2, p53 and anti-proliferation, Resveratrol, Sumoylation",
author = "Cheng, {Tsai Mu} and Chin, {Yu Tang} and Yih Ho and Chen, {Yi Ru} and Yang, {Yung Ning} and Yang, {Yu Chen} and Shih, {Ya Jang} and Lin, {Ting I.} and Lin, {Hung Yun} and Davis, {Paul J.}",
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TY - JOUR

T1 - Resveratrol induces sumoylated COX-2-dependent anti-proliferation in human prostate cancer LNCaP cells

AU - Cheng, Tsai Mu

AU - Chin, Yu Tang

AU - Ho, Yih

AU - Chen, Yi Ru

AU - Yang, Yung Ning

AU - Yang, Yu Chen

AU - Shih, Ya Jang

AU - Lin, Ting I.

AU - Lin, Hung Yun

AU - Davis, Paul J.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - Inducible COX-2

KW - p53 and anti-proliferation

KW - Resveratrol

KW - Sumoylation

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