Oestrogen inhibits resveratrol-induced post-translational modification of p53 and apoptosis in breast cancer cells

S. Zhang, H. J. Cao, F. B. Davis, H. Y. Tang, P. J. Davis, H. Y. Lin

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Resveratrol, a naturally occurring stilbene, induced apoptosis in human breast cancer MCF-7 cells. The mechanism of this effect was dependent on mitogen-activated protein kinase (MAPK, ERK1/2) activation and was associated with serine phosphorylation and acetylation of p53. Treatment of MCF-7 cells with resveratrol in the presence of 17β-oestradiol (E 2) further enhanced MAPK activation, but E 2 blocked resveratrol-induced apoptosis, as measured by nucleosome ELISA and DNA fragmentation assays. E 2 inhibited resveratrol-stimulated phosphorylation of serines 15, 20 and 392 of p53 and acetylation of p53 in a concentration- and time-dependent manner. These effects of E 2 on resveratrol action were blocked by ICI 182,780 (ICI), an inhibitor of the nuclear oestrogen receptor-α (ER). ICI 182,780 did not block the actions of resveratrol, alone. Electrophoretic mobility studies of p53 binding to DNA and of p21 expression indicated that E 2 inhibited resveratrol-induced, p53-directed transcriptional activity. These results suggest that E 2 inhibits p53-dependent apoptosis in MCF-7 cells by interfering with post-translational modifications of p53 which are essential for p53-dependent DNA binding and consequent stimulation of apoptotic pathways. These studies provide insight into the complex pathways by which apoptosis is induced by resveratrol in E 2-depleted and -repleted environments.

Original languageEnglish
Pages (from-to)178-185
Number of pages8
JournalBritish Journal of Cancer
Volume91
Issue number1
DOIs
Publication statusPublished - Jul 5 2004
Externally publishedYes

Keywords

  • Apoptosis
  • Breast cancer
  • MCF-7 cells
  • Mitogen-activated protein kinase
  • Oestrogen
  • p53
  • Resveratrol

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Oestrogen inhibits resveratrol-induced post-translational modification of p53 and apoptosis in breast cancer cells'. Together they form a unique fingerprint.

  • Cite this