Drug interactions with perfluorooctanoic acid and perfluorooctane sulfonate in cytotoxic activity against prostate cancer - in vitro studies

Poly- and perfluoroalkyl substances (PFAS), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are persistent environmental pollutants with potential toxicological effects on human health. The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines. Three cell lines were used in the study: two human prostate cancer cells (DU-145 and PC3) and one human normal prostate cell line (PNT1A). Using dose-response experiments, it was observed that PFAS had differential effects on cancer and normal cells. At low concentrations, PFOA and PFOS stimulated the proliferation of cancer cells, particularly PC3, while higher concentrations led to reduced viability. In normal cells, PFOS exhibited greater cytotoxicity compared to PFOA. Furthermore, PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells. Similarly, PFOA diminished cabazitaxel effectiveness in DU-145 cells, suggesting PFAS-drug interactions may depend on the cell type, drug, and PFAS concentration. Results suggest that PFAS may influence cellular processes through receptor-mediated pathways, oxidative stress modulation, and protein binding, altering drug bioavailability and cellular uptake. The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells. These findings raise concerns about the potential risks associated with PFAS exposure, particularly in the context of cancer treatment. Future studies should focus on long-term, low-dose PFAS exposure, the use of primary cells, and the molecular mechanisms driving these interactions to better inform therapeutic strategies.