Antiproliferative Effect and Cell Cycle Modulation by Melatonin on GH₃ Cells

We have investigated the effect of melatonin on cell proliferation and modulation, in the GH₃ experimental rat pituitary cell line; the expression of oncogenes c-myc, c-jun and the tumor suppressor gene p53 were also analyzed basally and after exposure to melatonin (10–⁶, 10–⁸ and 10–¹⁰ M). Melatonin exhibited an antiproliferative effect at all the doses tested, decreasing the proliferating index by 50%. After exposure to melatonin, a decrease in Ki67 and Proliferation cell nuclear antigen occurred acute- and transiently (at 2 h) after a single dose which recovered at 4 h, as well as chronically after repeated 12-hour doses which persisted at 48 h; a similar behavior was observed both acute- and chronically for c-myc and c-jun, while it was opposite for p53, rising acute- and transiently as well as after repeated exposure. These results demonstrate that melatonin modulates the proliferation mechanisms of the GH₃ cells.