Effects of estradiol, PCB3, and their hydroxylated metabolites on proliferation, cell cycle, and apoptosis of human breast cancer cells

摘要

Certain estradiol metabolites and industrial pollutants, like polychlorinated biphenyls, may play a more important role in enhancing breast cancer risk than 17β-estradiol. The aim of this study was to compare the effects of 17β-estradiol (E2) with that of the air pollutant 4-chlorobiphenyl (PCB3) and four of their hydroxylated metabolites on cell cycle, proliferation, and apoptosis in MCF-7 human breast cancer cells at concentrations of 0.1-10 nM (E2, 2-OH-E2, and 4-OH-E2) and 0.3-300 nM (PCB3, 4-OH-PCB3, and 3,4-diOH-PCB3) and 24-260 h of exposure. E2 increased cell proliferation and cells in S-phase at all time points. 2-OH-E2 and 4-OH-E2 had no effect on the cell cycle, but a stimulatory action on cell proliferation from 72 to 260 h of exposure to 4-OH-E2 and at 260 h to 2-OH-E2 was seen. E2 and its metabolites had no effect on apoptosis. PCB3 and 4-OH-PCB3 showed no effect on proliferation, apoptosis or cell cycle distribution at any concentration and time point. Longer time exposures to 3,4-di-OH-PCB at 300 nM caused a decrease of cells and an increase in G2/M and apoptotic cells. These results confirm the proliferative effect of E2 and its metabolite 4-OH-E2 in estrogen receptor positive breast cancer cells, but show no mitogenic activity for PCB3 and 4-OH-PCB3. However, the cell cycle and apoptosis effects of 3,4-diOH-PCB3 need further analysis.