Endocrine Abstracts

Fenhexamid (Fen) and cyprodinil (Cyp) are antifungal agents used in agricultural applications. In this study, to examine the effects of two-pesticides on cancer cell viability and metastasis via estrogen receptor pathway, the ER positive-MCF-7 and ER negative-MDA-MB-231 breast cancer cells were used. MCF-7 and MDA-MB-231 were cultured with 0.1% DMSO (control), 17β-estradiol (E₂; 1×10⁻⁹ M), Fen (10⁻⁵–10⁻⁷ M), Cyp (10⁻⁵–10⁻⁷ M) in the absence or presence of ICI 182,780 (ER antagonist). As results, in MTT assay, two-pesticides increased MCF-7 viability about two times compared to control like E₂ (about 3.5 times). But, when the respective treatment was co-treated with ICI 182,780, MCF-7 cell viability was maintained at the control level. However, MDA-MB-231 cell viability was not affected by E₂ or two-pesticides compared to control. In colony formation assay, MCF-7 cells did form the colony by treatment of E₂ and antifungal agents, but MDA-MB-231 cells did not form. However, E₂ and antifungal agents in the presence of ICI 182,780 did not induce the formation of MCF-7 colony. To examine the morphology change, MCF-7 and MDA-MB-231 cells were incubated on E₂ and two-pesticides in the absence or presence of ICI 182,780. As a result, morphology of MCF-7 cells was changed sharper by E2 and two-pesticides than control or group of co-treated with ICI 182,780. However, morphology of MDA-MB-231 cells by E2 and two-pesticides or co-treatment of ICI 182,780 was the same compared with control. In wound-healing scratch assay, the scratched distance was reduced by MCF-7 cells treated with E2 or two-pesticides compared with control. However, the scratched distance by MCF-7 cells co-treated with ICI 182,780 and MDA-MB-231 cells treated with E₂ or two-pesticides were maintained to the level of control. In migration assay, MCF-7 cells treated with E₂ or two-pesticides migrated more than 5 times compared with control and co-treatment with ICI182,780 inhibited migration of MCF-7 cells. The migration ratio of MDA-MB-231 cells by E2 or two-pesticides was similar to control. These results imply that the two-pesticides may have cancer progression effect by increasing cell viability and migration via ER dependent pathway. Based on this result, we will identify the mechanism related with metastasis of two-pesticides via ER pathway and confirm their effect by using xenografted mouse models in which MCF-7 cells are subcutaneously injected or are injected into mammary fat pad.