Treatment of MCF-7 and T47D human breast cancer cells with 3′,4′-dimethoxyflavone (3′,4′-DMF) alone did not induce CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity or reporter gene activity in cells transfected with an aryl hydrocarbon (Ah)-responsive construct (pRNH11c). In contrast, 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced up to a 50- to 80-fold increase in EROD and reporter gene activity in MCF-7 and T47D cells. In cells cotreated with 1 nM TCDD plus 0.1-10 μM 3′,4′-DMF, there was a concentration-dependent decrease in the TCDD-induced responses, with 100% inhibition observed at the 10 μM concentration. Gel mobility shift assays using rat liver cytosol and breast cancer cell nuclear extracts showed that 3′,4′-DMF alone did not transform the AhR to its nuclear binding form, but inhibited TCDD-induced AhR transformation in rat liver cytosol and blocked TCDD-induced formation of the nuclear AhR complex in MCF-7 and T47D cells. TCDD also inhibited estrogen-induced transactivation in MCF-7 cells, and this response was also blocked by 3′,4′-DMF, confirming the AhR antagonist activity of this compound in breast cancer cells.
- Breast cancer cells
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