Low-dose BPA and its substitute BPS promote ovarian cancer cell stemness via a non-canonical PINK1/p53 mitophagic signaling.

Abstract

The environmental toxicity of bisphenol A (BPA) and its analog like bisphenol S (BPS) have drawn wide attention, but their roles in cancer progression remain controversial. Here, we investigated the effect of BPA/BPS on the development of ovarian cancer. Human internal BPA/BPS exposure levels were analyzed from NHANES 2013-2016 data. We treated human ovarian cancer cells with 0-1000 nM BPA/BPS and found that 100 nM BPA/BPS treatment significantly increased Cancer Stem Cell (CSC) markers expression including OCT4, NANOG and SOX2. Cancer cell stemness evaluation induced by BPA/BPS was notably attenuated by the knockdown of PINK1 or Mdivi-1 treatment. The activation of PINK1 initiated mitophagy by inhibiting p-p53 nuclear translocation in a non-canonical manner. In vivo studies validated that BPA/BPS-exposed mice have higher tumor metastasis incidence compared with the control group, while mitophagy inhibition blocked such a promotion effect. In addition, CSC markers such as SOX2 had been found to be overexpressed in the tumor tissues of BPA/BPS exposure group. Taken together, the findings herein first provide the evidence that environmentally relevant BPA/BPS exposure could enhance ovarian cancer cell stemness through a non-canonical PINK1/p53 mitophagic pathway, raising concerns about the potential population hazards of BPA and other bisphenol analogs.

• Authors: Xiaoyu Yuan, Kelie Chen, Fang Zheng, Sinan Xu, Yating Li, Yuwei Wang, Heng Ni, Fang Wang, Zhenyan Cui, Yuheng Qin, Dajing Xia, Yihua Wu
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 452 Pg. 131288 (06 15 2023) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 36989771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• bisphenol A
• Tumor Suppressor Protein p53
• Mdivi-1
• Benzhydryl Compounds
• bis(4-hydroxyphenyl)sulfone
• Protein Kinases

Topics

• Humans
• Animals
• Mice
• Female
• Tumor Suppressor Protein p53 (genetics)
• Nutrition Surveys
• Benzhydryl Compounds (toxicity)
• Ovarian Neoplasms
• Protein Kinases