Endocrine Abstracts

Triclosan (TCS) is an endocrine-disrupting chemical and has a potential to increase progression of hormone responsive cancers as does 17β-estradiol (E₂). 3,3′-diindolylmethane (DIM), a phytoestrogen, has been known to have anticancer activity. In this study, we examined the anti-proliferative and anti-epithelial-mesenchymal transition (EMT) effects of DIM on TCS or E₂-induced EMT of MCF-7 breast cancer cells, which express estrogen receptors (ERs). In MTT assay, TCS (10-4-10-7 M) induced growth of MCF-7 cells compared to a control (DMSO) like E₂ (a positive control, 10–9 M), which was antagonized by addition of ICI 182,720 (10-8 M), suggesting that the cell proliferation effect induced by TCS appears to be mediated by an ER-dependent manner. On the contrary, DIM (20–50 μM) significantly reduced the increased viability of MCF-7 cells induced by TCS or E₂. In a scratch assay, TCS enhanced migration of MCF-7 cells like E₂, but co-treatment of DIM or ICI 182,720 reduced the migration ability of TCS and E₂ to a control level. Next, we measured TCS or E2-induced alterations in mRNA and protein expression levels of EMT related markers, i.e., E-cadherin, N-cadherin, snail and slug by reverse transcription (RT)-PCR and western blot assay. mRNA and protein expression of E-cadherin was declined while N-cadherin, snail, and slug expressions were increased by TCS or E₂, indicating that TCS induced EMT process in MCF-7 cells like E₂. Differently, DIM was shown to adversely affect the expression of EMT markers induced by TCS or E₂. Taken together, these results present that DIM effectively inhibits the cell growth and EMT process of MCF-7 cells increased by TCS or E2. Based on these in vitro results, in vivo effect of TCS and DIM on tumor growth and EMT process will be examined in a xenografted mouse model transplanted with MCF-7 breast cancer cells.