Bisphenol A modulates colorectal cancer protein profile and promotes the metastasis via induction of epithelial to mesenchymal transitions.

Abstract

More and more evidences indicate that endocrine disruptor chemicals such as bisphenol A (BPA) can act as carcinogens and enhance susceptibility to tumorigenesis. Although the gut is in direct contact with orally ingested BPA, effects of BPA on occurrence and development of colorectal cancer remain an unexplored endpoint. Colorectal cancer SW480 cells treated with nanomolar (10(-8) M) or greater (10(-5) M) concentrations of BPA were compared with responses of a control group. Proteomic study revealed that more than 56 proteins were modulated following exposure to BPA, which are relevant to structure, motility and proliferation of cells, production of ATP, oxidative stress, and protein metabolism. Further studies revealed that BPA increased migration and invasion and triggered transformations from epithelial to mesenchymal transitions (EMTs) of colorectal cancer cells, which was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin with a concomitant decrease of E-cadherin. Accordingly, BPA treatment increased the expression of transcription factor Snail. Furthermore, signal AKT/GSK-3β-mediated stabilization of Snail is involved during BPA-induced EMT of colon cancer cells. Our study first demonstrated that the xenoestrogen BPA at nanomolar and greater concentrations modulates the protein profiles and promotes the metastasis of colorectal cancer cells via induction of EMT.

• Authors: Zhuo-Jia Chen, Xiang-Ling Yang, Hao Liu, Wei Wei, Kun-Shui Zhang, Hong-Bin Huang, John P Giesy, Huan-Liang Liu, Jun Du, Hong-Sheng Wang
• Journal: Archives of toxicology (Arch Toxicol) Vol. 89 Issue 8 Pg. 1371-81 (Aug 2015) ISSN: 1432-0738 [Electronic] Germany
• PMID: 25119493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Endocrine Disruptors
• Neoplasm Proteins
• Phenols
• Proteome
• bisphenol A

Topics

• Apoptosis (drug effects)
• Benzhydryl Compounds (toxicity)
• Blotting, Western
• Cell Culture Techniques
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (metabolism, pathology)
• Dose-Response Relationship, Drug
• Endocrine Disruptors (toxicity)
• Epithelial-Mesenchymal Transition (drug effects)
• Flow Cytometry
• Humans
• Neoplasm Metastasis
• Neoplasm Proteins (metabolism)
• Phenols (toxicity)
• Proteome (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization