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.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Benzhydryl Compounds / antagonists & inhibitors
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Benzhydryl Compounds / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cyclin D1 / agonists
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Cyclin D1 / antagonists & inhibitors
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Down-Regulation / drug effects
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Estradiol / chemistry
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Estradiol / metabolism
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Estrogen Receptor alpha / agonists
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Estrogen Receptor alpha / antagonists & inhibitors*
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / metabolism
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Estrogens, Non-Steroidal / antagonists & inhibitors
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Estrogens, Non-Steroidal / pharmacology
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Insulin Receptor Substrate Proteins / agonists
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Insulin Receptor Substrate Proteins / antagonists & inhibitors
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Insulin Receptor Substrate Proteins / genetics
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Insulin Receptor Substrate Proteins / metabolism
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Neoplasm Proteins / agonists
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / metabolism
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Phenols / antagonists & inhibitors
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Phenols / pharmacology
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Phosphorylation / drug effects
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Phytoestrogens / pharmacology*
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Protein Processing, Post-Translational / drug effects
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Receptor, IGF Type 1 / agonists
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Receptor, IGF Type 1 / antagonists & inhibitors*
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Receptor, IGF Type 1 / genetics
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Receptor, IGF Type 1 / metabolism
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Resveratrol
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Signal Transduction / drug effects*
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Stilbenes / pharmacology*
Substances
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Antineoplastic Agents, Phytogenic
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Benzhydryl Compounds
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CCND1 protein, human
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ESR1 protein, human
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Estrogen Receptor alpha
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Estrogens, Non-Steroidal
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IRS1 protein, human
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Insulin Receptor Substrate Proteins
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Neoplasm Proteins
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Phenols
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Phytoestrogens
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Stilbenes
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Cyclin D1
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Estradiol
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Receptor, IGF Type 1
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bisphenol A
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Resveratrol