ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P999 | DOI: 10.1530/endoabs.63.P999

Low doses of persistent organic pollutants (PFOA and PCB153) increase the tumor aggressiveness of hormone-dependent cancer cells

Aurélie Charazac1, Charlotte Hinault1,2, Frédéric Bost1, Stéphan Clavel1 & Nicolas Chevalier1,3

1C3M Inserm U1065 UCA, Nice, France; 2Laboratoire de Biochimie-Hormonologie CHU de Nice – UCA, Nice, France; 3Département d’Endocrinologie-Diabétologie-Médecine de la Reproduction CHU de Nice UCA, Nice, France.

Persistent organic pollutants (POPs) are lipophilic chemicals that chronically accumulate in the body during lifetime from fetal life. Some POPs alter the endocrine metabolism and are considered as endocrine disrupting chemicals (EDCs). Human exposure to EDCs, even at low doses, raises some serious concerns for human health because they can participate in hormone-dependent cancer initiation and progression (prostate, breast, testis). These mostly non-metabolizable molecules are found in many daily products such as food preservatives and packaging, pesticides or residues and can accumulate in fat deposit of living organisms. A major scientific issue is thmus to be able to provide relevant tools for predictive analysis and to decipher more precisely biological mechanisms to evaluate EDCs risks. The aim of this work is to study the effects of four EDCs (Aldrin, BDE28, PCB153, PFOA), previously detected in the plasma of patients, on the aggressiveness of two human hormone-dependent cancer cell lines DU145 and MCF7, respectively for prostate and breast cancer. Each cell line was exposed to increasing doses of EDCs (10−12M to 10−6M) up to 72 h. Using videoimaging technology (Incucyte), we monitored proliferation, cytotoxicity and collective migration. We also assessed individual migration using Boyden chamber assays. Interestingly, we unraveled a pro-proliferative effect, with no cytotoxic effect, for PFOA and PCB153 at very low concentration (10−12M) in both cell types (DU145 and MCF7), while the same effects were observed only at high concentrations (10−6M) for aldrin and BDE28. We were also able to measure an increase in individual migration after PFOA or PCB153 exposure at the same concentration. To decipher the mechanisms implicated in this effect, we performed a human phospho-proteome which revealed a potential involvement of the PI3K-AKT-mTOR pathway in MCF7 cells. Our results demonstrate that PFOA an PCB153, at very low concentration, increase the aggressiveness of prostate and breast cancer cell lines suggesting that endocrine disruptors are potentially implicated in the progression of cancer during late stages of disease.

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