Bisphenol A modulates proliferation, apoptosis, and wound healing process of normal prostate cells: Involvement of G2/M-phase cell cycle arrest, MAPK signaling, and transcription factor-mediated MMP regulation

• Published in: Ecotoxicology and environmental safety 2023-01, Vol.249, p.114358, Article 114358
• Main Authors: Song, Jun-Hui, Hwang, Byungdo, Kim, Su-Bin, Choi, Yung Hyun, Kim, Wun-Jae, Moon, Sung-Kwon
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Benzhydryl Compounds - toxicity; Bisphenol A; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Proliferation; Humans; Male; Matrix Metalloproteinases; Mitogen-Activated Protein Kinase Kinases - metabolism; MMP-9; Prostate - cytology; Prostate - drug effects; Prostate cells; Transcription Factors - metabolism; Wound Healing - drug effects; Wound healing process
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.114358

Bisphenol A (BPA) is commonly used to produce epoxy resins and polycarbonate plastics. BPA is an endocrine-disrupting chemical that is leaked from the polymer and absorbed into the body to disrupt the endocrine system. Although BPA may cause cytotoxicity in the prostate, a hormone-dependent reproductive organ, its underlying mechanism has not yet been elucidated. Here, we investigated the effects of BPA on cell proliferation, apoptosis, and the wound healing process using prostate epithelial cells (RWPE-1) and stromal cells (WPMY-1). Observations revealed that BPA induced G2/M cell cycle arrest in both cell types through the ATM−CHK1/CHK2–CDC25c−CDC2 signaling pathway, and the IC50 values were estimated to be 150 μM. Furthermore, BPA was found to induce caspase-dependent apoptosis through initiator (caspase-8 and −9) and executioner (caspase-3 and −7) caspase cascades. In addition, BPA interfered with the wound healing process through inhibition of MMP-2 and − 9 expression, accompanied by reductions in the binding activities of AP-1 as well as NF-κB motifs. Phosphorylation of MAPKs was associated with the BPA-mediated toxicity of prostate cells. These results suggest that BPA exhibits prostate toxicity by inhibiting cell proliferation, inducing apoptosis, and interfering with the wound healing process. Our study provided new insights into the precise molecular mechanisms of BPA-induced toxicity in human prostate cells. [Display omitted] •BPA impeded normal prostate cell proliferation through G2/M-phase cell cycle arrest.•BPA induced G2/M-phase cell cycle arrest via ATM−CHK1/CHK2 −CDC25c−CDC2 signaling.•BPA induced apoptosis via caspase-dependent apoptosis signaling cascade.•BPA exposure upregulated MAPK signaling pathways in prostate cells.•BPA reduced wound healing process by transcription factor-mediated MMP regulation.