2,3,7,8-Tetrachlorodibenzo-p-dioxin as an antiproliferative agent in human breast cancer cells: Effects on insulin-induced cell proliferation

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) elicits a broad spectrum of antiestrogenic responses in MCF-7 human breast cancer cells. Treatment of the cells with insulin (0.001 - 10.0 μg/ml) caused a significant concentration-dependent increase in cell proliferation at concentrations of 0.01 - 10.0 μg/ml with a maximum response observed at 1.0 μg/ml. Treatment of the cells with TCDD (0.01 to 10 nM) caused some decrease in cell growth at the high concentrations. Cotreatment of the cells with insulin plus TCDD at several different concentrations showed that TCDD at a concentration as low as 0.1 nM inhibited insulin-induced cell proliferation. In a parallel study, insulin also caused a concentration-dependent increase in [³H]thymidine uptake into cellular DNA at concentrations of 0.01, 0.1 and 1.0 μg/ml and TCDD (0.1 nM) significantly inhibited this response at all 3 concentrations of insulin. These results illustrate the interaction between TCDD and insulin in MCF-7 cells and further extend the antimitogenic activity of TCDD in human breast cancer cell lines.