Low Doses of PFOA Promote Prostate and Breast Cancer Cells Growth through Different Pathways

Endocrine Disrupting Compounds (EDCs) are found in everyday products. Widely distributed throughout the environment, persistent organic pollutants (POPs) are a specific class of EDCs that can accumulate in adipose tissue. Many of them induce adverse effects on human health-such as obesity, fertility disorders and cancers-by perturbing hormone effects. We previously identified many compounds with EDC activity in the circulation of obese patients who underwent bariatric surgery. Herein, we analyzed the effects of four of them (aldrin, BDE28, PFOA and PCB153) on two cancer cell lines of hormone-sensitive organs (prostate and breast). Each cell line was exposed to serial dilutions of EDCs from 10^-6 M to 10^-12 M; cytotoxicity and proliferation were monitored using the IncuCyte^® technology. We showed that none of these EDCs induce cytotoxicity and that PFOA and PCB153, only at very low doses (10^-12 M), increase the proliferation of DU145 (prostate cancer) and MCF7 (breast cancer) cells, while the same effects are observed with high concentrations (10^-6 M) for aldrin or BDE28. Regarding the mechanistic aspects, PFOA uses two different signaling pathways between the two lines (the Akt/mTORC1 and PlexinD1 in MCF7 and DU145, respectively). Thus, our study demonstrates that even at picomolar (10^-12 M) concentrations PFOA and PCB153 increase the proliferation of prostate and breast cancer cell lines and can be considered possible carcinogens.