Effects of melatonin on proliferation of cancer cell lines

The pineal hormone melatonin has been reported to have in vitro antiproliferative 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 linked to the estrogen-receptor system. We tested the cytotoxic effects of melatonin 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 have 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 cytotoxic effect, which was not mediated by the estrogen-receptor or by protein tyrosine kinases and was not specific for breast cancer cell lines. Intracellular glutathione levels did not seem to play any role in the sensitivity 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 (physiological or supraphysiological) concentrations. The different experimental procedures that were utilized in the present study can partially explain the divergence between our results and the literature.