We analyzed whether polychlorinated biphenyls (PCBs) interfere with the activity of 17 β-estradiol in the proliferation and apoptosis of the MCF-7 cell line. MCF-7 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) without phenol red supplemented with 5% charcoal-treated fetal bovine serum (CD-FBS) for 3 days with 10 nM 17 β-estradiol or 0.1 µM, 0.5 µM and 1 µM of the tested PCB congeners (118, 138, 153 and 180), or both. Cell proliferation was determined by measuring 5-bromo-2'-deoxyuridine (BrdU) incorporation, and cell apoptosis was measured by caspase-9 activity. From the PCB congeners tested, PCB138 and 153 had the highest stimulatory effects on basal cell proliferation as well as the highest inhibitory actions on basal caspase-9 activity. The proliferative and anti-apoptotic actions of PCB138 and 153 were still observed in the presence of 17 β-estradiol, while the actions of PCB118 and 180 were reversed. In conclusion, the results of this study suggest the possibility that PCB138 and 153 contribute to the action of endogenous 17 β-estradiol on cell proliferation and apoptosis in the breast cancer cell line MCF-7.

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Recent results have shown that the level of gap junction coupling could modulate the induction of apoptotic reactions. We previously observed that 1H-[1,2, 4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a blocker of guanylyl cyclase, inhibited gap junction coupling and thereby promoted activation of characteristic apoptotic reactions such as chromatin condensation, DNA strand breaking, and formation of blebs in GFSHR-17 granulosa cells, the in vitro model for granulosa cells of the maturing ovular follicle. In the present report, we focus on the effects of ODQ with respect to the cell cycle in GFSHR-17 granulosa cells. In synchronised GFSHR-17 granulosa cells, the double whole-cell patch-clamp technique revealed that gap junction conductance in mitotic cells was reduced in comparison to cells in interphase. This reduction of gap junction conductance correlated with a reduction of non-phosphorylated Cx43 in mitotic cells. We compared the stimulation of apoptotic reactions by ODQ between cells in mitosis and in interphase. We observed that the induction of both chromatin condensation and DNA strand breaking by ODQ was increased in mitotic cells, as compared to cells in interphase. The effects of ODQ were not observed in HeLa cells that do not express connexins. The results indicate that reduction of gap junction coupling in mitotic GFSHR-17 granulosa cells depends on phosphorrylation of Cx43 and raises the sensitivity to stimulation of apoptosis. We propose that gap junction coupling is involved in regulation of apoptosis of granulosa cells in maturing ovular follicle.

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