Resveratrol regulates the cell viability promoted by 17β-estradiol or bisphenol A via down-regulation of the cross-talk between estrogen receptor α and insulin growth factor-1 receptor in BG-1 ovarian cancer cells

Food Chem Toxicol. 2013 Sep:59:373-9. doi: 10.1016/j.fct.2013.06.029. Epub 2013 Jun 27.

Abstract

Endocrine disrupting chemicals (EDCs) and estrogens appear to promote development of estrogen-dependent cancers, including breast and ovarian carcinomas. In this study, we evaluated the cell viability effect of BPA on BG-1 human ovarian cancer cells, along with the growth inhibitory effect of resveratrol (trans-3,4,5-trihydroxystilbene; RES), a naturally occurring phytoestrogen. In addition, we investigated the underlying mechanism(s) of BPA and RES in regulating the interaction between estrogen receptor alpha (ERα) and insulin-like growth factor-1 receptor (IGF-1R) signals, a non- genomic pathway induced by 17β-estradiol (E2). BPA induced a significant increase in BG-1 cell growth and up-regulated mRNA levels of ERα and IGF-1R. In parallel with its mRNA level, the protein expression of ERα was induced, and phosphorylated insulin receptor substrate-1 (p-IRS-1), phosphorylated Akt1/2/3, and cyclin D1 were increased by BPA or E2. However, RES effectively reversed the BG-1 cell proliferation induced by E2 or BPA by inversely down-regulating the expressions of ERα, IGF-1R, p-IRS-1, and p-Akt1/2/3, and cyclin D1 at both transcriptional and translational levels. Taken together, these results suggest that RES is a novel candidate for prevention of tumor progression caused by EDCs, including BPA via effective inhibition of the cross-talk of ERα and IGF-1R signaling pathways.

Keywords: Cell proliferation; ERα; Endocrine disrupting chemicals; IGF-1R; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Benzhydryl Compounds / antagonists & inhibitors
  • Benzhydryl Compounds / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin D1 / agonists
  • Cyclin D1 / antagonists & inhibitors
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Down-Regulation / drug effects
  • Estradiol / chemistry
  • Estradiol / metabolism
  • Estrogen Receptor alpha / agonists
  • Estrogen Receptor alpha / antagonists & inhibitors*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogens, Non-Steroidal / antagonists & inhibitors
  • Estrogens, Non-Steroidal / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Insulin Receptor Substrate Proteins / agonists
  • Insulin Receptor Substrate Proteins / antagonists & inhibitors
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Neoplasm Proteins / agonists
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Phenols / antagonists & inhibitors
  • Phenols / pharmacology
  • Phosphorylation / drug effects
  • Phytoestrogens / pharmacology*
  • Protein Processing, Post-Translational / drug effects
  • Receptor, IGF Type 1 / agonists
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Resveratrol
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Benzhydryl Compounds
  • CCND1 protein, human
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Estrogens, Non-Steroidal
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Neoplasm Proteins
  • Phenols
  • Phytoestrogens
  • Stilbenes
  • Cyclin D1
  • Estradiol
  • Receptor, IGF Type 1
  • bisphenol A
  • Resveratrol