Endocrine Abstracts

Previous studies suggest that environmental factors such as high levels of meat consumption, caffeine, cigarette smoking, pesticides, and endocrine disrupting chemicals (EDCs) may enhance the risk of breast cancer. The fludioxonil is an antifungal agent used in agricultural applications and present at measurable amounts in fruits and vegetables. In this study, the effects of fludioxonil on cancer cell viability and migration ability were examined in MCF-7 and T47D breast cancer cell with estrogen receptors and MDA-MB-231 breast cancer cell without estrogen receptors. The MCF-7, T47D and MDA-MB-231 cells were cultured with 0.1% DMSO (control), 17β-estradiol (E₂; 1×10⁻⁹ M), or fludioxonil (10^-5–10⁻⁸ M). As results, in MTT assay for 9 days, E₂ as a positive control markedly increased MCF-7 and T47D cell viability about 3.5 times and 2.2 times, and fludioxonil (10⁻⁵ M) also increased cell viability about 1.2 to 1.5 times compared to control. When the respective treatment was co-treated with ICI 182,780, an ER antagonist, MCF-7 and T47D cells viability were reversed to the level of control. However, the cell viability of MDA-MB-231cells was not changed by treatment of fludioxonil and co-treated with ICI 182,780, as did E₂. In the migration assay for 48h, MCF-7 cells and T47D cells were migrated to low chamber from upper chamber via to 0.8 μm pore. And migration of MCF-7 cells and T47D cells by E₂ or fludioxonil were inhibited by co-treatment of ICI 182,780. Although, the cell number of migration in MDA-MB-231 cells by treatment of E₂ or fludioxonil were not had the significance of result compare with 0.1% DMSO including co-treatment of ICI 182,780. These results imply that the fludioxonil may have breast cancer progression effect by increasing cell viability and migration via estrogen receptor dependent pathway. Therefore, we will have to confirm the molecular mechanism for support the change of cell viability and cell migration. And, based on this result, we will identify the mechanism related with estrogen receptor and PI3K/AKT pathway in vitro and confirm their effect by using xenografted or orthotopic mouse models in which MCF-7 or T47D cells are subcutaneously injected or are injected into mammary fat pad for 90 days.

Key words: Endocrine disruption; cell cycle gene; cell migration; fludioxonil; breast cancer; estrogen receptor pathway