The effect of indole-3-carbinol on the expression of CYP1A1, CYP1B1 and AhR genes and proliferation of MCF-7 cells.

Abstract

The influence of an antiestrogen, indole-3-carbinol (I3C) on the expression of CYP1A1, CYP1B1 and AhR genes was investigated in an attempt to establish whether I3C could increase the expression of genes involved in estrone metabolism. Another purpose was to examine the proliferation of an estrogen-dependent breast cancer cell (MCF-7 line) under the influence of I3C and both I3C and DDT. In MCF-7 cells incubated with I3C or I3C and DDT combined, quantitative RT-PCR analysis revealed a significant increase in the level of CYP1A1, AhR, and CYP1B1 transcripts. The proliferation rate of MCF-7 cells was increased by treatment with DDT or estradiol (E2), whereas I3C did not affect the proliferation of MCF-7 cells but greatly reduced the stimulatory effect of DDT, and abolished the effect of E2. The level of p21 transcript, encoding p21 protein involved in the cell cycle, was increased several-fold by I3C comparing to its level in cells incubated with estradiol or DDT. The results suggest that the proliferation of MCF-7 cells is accompanied not only by expression of genes encoding cytochromes involved in estrogen metabolism, but also by changes in the expression of other genes including that encoding p21 protein involved in the cell cycle.