Bisphenol S (BPS) is extensively utilized in various commercial and manufacturing products, including cleaning detergents, plating solvents, phenolic resins, and thermal paper. Previous studies have demonstrated that BPS is closely associated with acute cytotoxicity, neurotoxicity, immunotoxicity, and cardiovascular toxicity. Recent research has also linked BPS to the progression of estrogen-related tumors. In ovarian cancer, BPS has been shown to enhance cancer cell stemness by upregulating the expression of cancer stem cell (CSC) markers. The current study aims to investigate whether BPS has similar effects on triple-negative breast cancer (TNBC). To this end, two TNBC cell lines, MDA-MB-231 and SUM159, were exposed to doses of BPS that are relevant to human and environmental exposure levels.
The study found that exposure to BPS significantly enhances the stemness properties of TNBC cells, as evidenced by increased expression of stem cell markers such as CD44, ALDH1, OCT4, and SOX2. The enhanced stemness properties conferred by BPS exposure translated into increased tumorigenic potential, demonstrated by increased migration and invasion, along with upregulation of key markers like vimentin and snail.
The authors investigated the Sonic Hedgehog (SHH) pathway as a potential mechanism for the increased stemness observed after BPS exposure, given its essential role in regulating multiple cancer processes, including stemness. BPS was shown to activate the SHH signaling pathway, specifically by upregulating Gli1, a key transcription factor in this pathway. To further validate Shh as a potential mechanism, they combined BPS exposure with inhibition of the SHH pathway or downregulation of Gli1. In these experiments, the authors observed decreased expression of OCT4, ALDH1A1, KLF4, Nanog, and SOX2 proteins, as well as reduced cell sphere formation and self-renewal capabilities.
The findings suggest that BPS, a common industrial chemical, could contribute to the aggressiveness of TNBC by promoting stem-like characteristics. This highlights the potential risks associated with BPS exposure and underscores the need for further research into its effects on cancer progression and potential therapy resistance.
Effects of SHH signaling pathway inhibition on TNBC cell stemness under BPS treatment.
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