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Low-dose BPA and its substitute BPS promote ovarian cancer cell stemness via a non-canonical PINK1/p53 mitophagic signaling.
- Source :
-
Journal of Hazardous Materials . Jun2023, Vol. 452, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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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. [Display omitted] • Environmental relevant BPA/BPS exposure enhances ovarian cancer cell stemness. • Low-dose BPA/BPS upregulates PINK1 expression. • p53 rather than Parkin pathway is activated under low-dose BPA/BPS exposure. • BPA/BPS promotes ovarian cancer in vivo metastasis in a mitophagy-dependent manner. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043894
- Volume :
- 452
- Database :
- Academic Search Index
- Journal :
- Journal of Hazardous Materials
- Publication Type :
- Academic Journal
- Accession number :
- 163292051
- Full Text :
- https://doi.org/10.1016/j.jhazmat.2023.131288