Ws. Baldwin et al., MELATONIN DOES NOT INHIBIT ESTRADIOL-STIMULATED PROLIFERATION IN MCF-7 AND BG-1 CELLS, Carcinogenesis (New York. Print), 19(11), 1998, pp. 1895-1900
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.