Effects of melatonin on proliferation of cancer cell lines

The pineal hormone melatonin has been reported to have in vitro antiprolife rative effects on estrogen receptor-positive human breast cancer cell lines at concentrations near to plasma physiological concentrations (1 x 10(-11) to 1 x 10(-9) M). Its growth inhibitory actions have been thought to be li nked to the estrogen-receptor system. We tested the cytotoxic effects of me latonin on MCF-7 and T47D human breast cancer cell lines by using the SRB ( sulforhodamine-B), XTT-tetrazolium, and bromodeoxyuridine (BrdU) assays in 96-well microtiter plates. After a 3 or 4 day exposure, melatonin did not h ave any significant effect on breast cancer cell proliferation and survival in doses up to 1 x 10(-4) M. Doses higher than 1 mM exhibited a potent cyt otoxic effect, which was not mediated by the estrogen-receptor or by protei n tyrosine kinases and was not specific for breast cancer cell lines. Intra cellular glutathione levels did not seem to play any role: in the sensitivi ty of breast cancer cells to melatonin, since the addition of L-buthionine- [S,R]-sulfoximine, ethacrynic acid, or exogenous glutathione did not modify our results. We conclude that under our experimental conditions melatonin has no inhibitory effects on human breast cancer cells at low (physiologica l or supraphysiological) concentrations. The different experimental procedu res that were utilized in the pre:;ent study can partially explain the dive rgence between our results and the literature.