MELATONIN DOES NOT INHIBIT ESTRADIOL-STIMULATED PROLIFERATION IN MCF-7 AND BG-1 CELLS

Melatonin, an indolic pineal hormone, is produced primarily at night i n mammals and is important in controlling biological rhythms, Previous research suggested that melatonin can attenuate proliferation in the estrogen-responsive MCF-7 breast cancer cell line. We tested whether t hese antiproliferative effects may have physiological consequences upo n two estrogen-responsive cell lines, MCF-7 (a breast cancer cell line ) and BG-1 (an ovarian adenocarcinoma cell line). Melatonin (10(-9)-10 (-5) M) attenuated proliferation of MCF-7 and BG-1 cells by >20% in th e absence of estrogen, However, 17 beta-estradiol exposure negated the ability of melatonin to inhibit proliferation. To substantiate this f inding, cells were estrogen starved followed by multiple treatments wi th estradiol and melatonin, Melatonin did not inhibit estradiol-stimul ated proliferation under this protocol. Estradiol increased MCF-7 and BG-1 cell cycle transition from G(1) to S phase, however, melatonin di d not inhibit this transition nor did it down-regulate estradiol-induc ed pS2 mRNA levels measured by northern blotting, further indicating t hat melatonin was unable to attenuate estradiol-induced proliferation and gene expression. We also examined the effects of melatonin on estr adiol-induced proliferation in MCF-7 cell xenografts in athymic nude m ice. Melatonin at a dose 28 times greater than 17 beta-estradiol did n ot inhibit estradiol-induced proliferation in vivo. Furthermore, pinea lectomy did not increase proliferation. Therefore, we conclude that me latonin does not directly inhibit estradiol-induced proliferation.