Université Côte d'Azur, INSERM U1065, C3M, Bâtiment Universitaire Archimed, 151 Route de Saint-Antoine de Ginestière, BP 2 3194, CEDEX 3, 06204 Nice, France.
Équipe Labelisée Ligue Nationale Contre le Cancer.
Int J Mol Sci. 2022 Jul 18;23(14):7900. doi: 10.3390/ijms23147900.
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 M to 10 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 M), increase the proliferation of DU145 (prostate cancer) and MCF7 (breast cancer) cells, while the same effects are observed with high concentrations (10 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 M) concentrations PFOA and PCB153 increase the proliferation of prostate and breast cancer cell lines and can be considered possible carcinogens.
内分泌干扰化合物 (EDCs) 存在于日常产品中。广泛分布于环境中的持久性有机污染物 (POPs) 是 EDCs 的一个特定类别，它们可以在脂肪组织中积累。其中许多通过干扰激素作用对人类健康产生不利影响，如肥胖、生育障碍和癌症。我们之前在接受减肥手术的肥胖患者的循环中发现了许多具有 EDC 活性的化合物。在此，我们分析了四种化合物（艾氏剂、BDE28、PFOA 和 PCB153）对两种激素敏感器官（前列腺和乳腺）的癌细胞系的影响。每个细胞系都暴露于从 10 M 到 10 M 的 EDC 系列稀释液中；使用 IncuCyte 技术监测细胞毒性和增殖。我们表明，这些 EDC 都没有诱导细胞毒性，而 PFOA 和 PCB153 仅在非常低的剂量（10 M）下，才会增加 DU145（前列腺癌）和 MCF7（乳腺癌）细胞的增殖，而艾氏剂或 BDE28 的高浓度（10 M）也会产生相同的效果。关于机制方面，PFOA 在两条线上使用两种不同的信号通路（Akt/mTORC1 和 PlexinD1，分别在 MCF7 和 DU145 中）。因此，我们的研究表明，即使在皮摩尔（10 M）浓度下，PFOA 和 PCB153 也会增加前列腺癌和乳腺癌细胞系的增殖，并且可以被认为是潜在的致癌物质。
