Antiproliferative effect and cell cycle modulation by melatonin on GH(3) cells

We have investigated the effect of melatonin on cell proliferation and modu lation, in the GH(3) experimental rat pituitary cell line; the expression o f oncogenes c-myc, c-jun and the tumor suppressor gene p53 were also analyz ed basally and after exposure to melatonin (10(-6), 10(-8) and 10(-10) M). Melatonin exhibited an antiproliferative effect at all the doses tested, de creasing the proliferating index by 50%, After exposure to melatonin, a dec rease in Ki67 and Proliferation cell nuclear antigen occurred acute- and tr ansiently (at 2 h) after a single dose which recovered at 4 h, as well as c hronically 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, whil e it was opposite for p53, rising acute- and transiently as well as after r epeated exposure. These results demonstrate that melatonin modulates the pr oliferation mechanisms of the GH3 cells. Copyright (C) 2000 S. Karger AG,Ba sel.