Effects of melatonin on the cell cycle kinetics and “estrogen‐rescue” of MCF‐7 human breast cancer cells in culture

Abstract

Cos S, Blask DE, Lemus-Wilson A, Hill AB. Effects of melatonin on the cell cycle kinetics and “estrogen-rescue of MCF-7 human breast cancer cells in culture. J Pineal Res 1991:10:3642. Melatonin has been shown to have a direct inhibitory action on the proliferation of estrogen-responsive MCF-7 human breast cancer cells in culture. In the present study, we examined by flow cytometry whether this inhibitory effect might be exerted on the G₁ phase of the cell cycle, thus causing a transition delay into the S phase. In order to further verify this hypothesis we tested the ability of estradiol to “rescue” MCF-7 cells from melatonin inhibition, and the potential of this indoleamine to block the ability of estradiol to rescue the cells from tamoxifen inhibition. Following five days of incubation, melatonin (10^-9M) increased the fraction of cells in G₁ of the cell cycle while simultaneously causing a 50% reduction in the proportion of cells in S phase. The antiproliferative effect of melatonin (11^-5M) was prevented by the simultaneous treatment of the cells with estradiol (10^-8M) in clonogenic soft agar culture, or reversed by the addition of estradiol to cells previously incubated with and inhibited by melatonin (10^-9M) in monolayer culture. Additionally, melatonin blocked the estrogen-rescue of tamoxifen-inhibited cells in both types of culture systems. These results support the hypothesis that the antiproliferative effect of melatonin, like tamoxifen, is cell cycle specific by causing a G₁-S transition delay. These results also indicate an important interaction of melatonin with estrogen-mediated mechanisms of MCF-7 cell proliferation.