Impact of organic pollutants on phenotype and gene expression in human breast cancer cells

Human exposure to industrial chemical compounds is widespread and, although often beneficial, prolonged contact may contribute to disease development, including cancer. While many studies have shown organic pollutants (OP) are cytotoxic, few have explored how long-term exposure alters cell phenotype. Therefore, the current study investigated whether exposure to the OP perfluorooctanoic acid (Pfoa: 0.01, 0.1, and 1 μM), bisphenol A (Bpa: 0.1 and 1 μM), methoxychlor (Mtx: 0.1 and 1 μM), and benzophenone-1 (Bp1: 1 and 10 μM) modulates the phenotype of MCF7 human breast cancer cells and MCF10A normal breast epithelial cells. MCF7 cells were exposed to environmentally relevant concentrations of the OP for 24 h and 15 days. Cell viability, proliferation, colony formation, drug-efflux activity, and gene expression were assessed. A modulation of MCF7 breast cancer cell phenotype was observed, with increased proliferation and colony formation (Pfoa, Bpa, Mtx, Bp-1), particularly at 15-day exposure and with expression of genes involved in cell survival, proliferation, differentiation, and chemoresistance (STAT3 and VEGFA [Bpa, Mtx, Bp-1], BRCA1 [Bp1], ESR2 [Pfoa, Bpa], ABCG2 [Pfoa]). No effects on cell migration and drug-efflux activity were observed. Likewise, an increase in cell proliferation also occurred for MCF10A nontumor cells (Bpa, Mtx, Bp-1), but these effects were usually less pronounced than those observed in MCF7 cells. Pan-cancer analysis revealed a negative correlation between the expression of STAT3, VEGFA, ESR2, and ABCG2 and breast cancer patient survival. These findings suggest that low-concentration, prolonged exposure to OP may promote tumor progression and aggressiveness in breast cancer, potentially undermining therapeutic outcomes.