Genistein suppressed epithelial-mesenchymal transition and migration efficacies of BG-1 ovarian cancer cells activated by estrogenic chemicals via estrogen receptor pathway and downregulation of TGF-β signaling pathway.

Abstract

BACKGROUND:

Epithelial-mesenchymal transition (EMT), which is activated by 17β-estradiol (E2) in estrogen-responsive cancers, is an important process in tumor migration or progression. As typical endocrine disrupting chemicals (EDCs), bisphenol A (BPA) and nonylphenol (NP) have a potential to promote EMT and migration of estrogen-responsive cancers. On the contrary, genistein (GEN) as a phytoestrogen is known to have chemopreventive effects in diverse cancers.

METHODS:

In the present study, the effects of BPA and GEN on EMT and the migration of BG-1 ovarian cancer cells and the underlying mechanism were investigated. ICI 182,780, an estrogen receptor (ER) antagonist, was co-treated with E2 or BPA or NP to BG-1 cells to identify the relevance of ER signaling in EMT and migration.

RESULTS:

As results, E2 and BPA upregulated the protein expression of vimentin, cathepsin D, and MMP-2, but downregulated the protein expression of E-cadherin via ER signaling pathway, suggesting that E2 and BPA promote EMT and cell migration related gene expressions. However, the increased protein expressions of vimentin, cathepsin D, and MMP-2 by E2, BPA, or NP were reduced by the co-treatment of GEN. In a scratch assay, the migration capability of BG-1 cells was enhanced by E2, BPA, and NP via ER signaling but reversed by the co-treatment of GEN. In the protein expression of SnoN and Smad3, E2, BPA, and NP upregulated SnoN, a negative regulator of TGF-β signaling, and downregulated pSmad3, a transcription factor in the downstream pathway of TGF-β signaling pathway, suggesting that E2, BPA, and NP simultaneously lead to the downregualtion of TGF-β signaling in the process of induction of EMT and migration of BG-1 cells via ER signaling. On the other hand, the co-treatment of GEN reversed the downregulation of TGF-β signaling by estrogenic chemicals.

CONCLUSION:

Taken together, GEN suppressed EMT and migration capacities of BG-1 ovarian cancer cells enhanced by E2, BPA, and NP via ER signaling and the downregulation of TGF-β signal.

• Authors: Ye-Seul Kim, Kyung-Chul Choi, Kyung-A Hwang
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 22 Issue 11 Pg. 993-9 (Oct 15 2015) ISSN: 1618-095X [Electronic] Germany
• PMID: 26407941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier GmbH. All rights reserved.

Chemical References

• Benzhydryl Compounds
• Intracellular Signaling Peptides and Proteins
• Phenols
• Proto-Oncogene Proteins
• Receptors, Estrogen
• SKIL protein, human
• SMAD3 protein, human
• Smad3 Protein
• Transforming Growth Factor beta
• Vimentin
• Genistein
• CTSD protein, human
• Cathepsin D
• MMP2 protein, human
• Matrix Metalloproteinase 2
• bisphenol A

Topics

• Benzhydryl Compounds (toxicity)
• Cathepsin D (metabolism)
• Cell Line, Tumor (drug effects)
• Cell Movement (drug effects)
• Down-Regulation
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Genistein (pharmacology)
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Ovarian Neoplasms (metabolism, pathology)
• Phenols (toxicity)
• Proto-Oncogene Proteins (metabolism)
• Receptors, Estrogen (metabolism)
• Signal Transduction (drug effects)
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta (metabolism)
• Vimentin (metabolism)