Antiproliferative action of melatonin on human prostate cancer LNCaP cells

Recent experimental evidence suggests that melatonin, the major pineal horm one, might possess oncostatic properties. The present experiments were perf ormed to verify whether melatonin might modulate the growth of androgen-dep endent prostate cancer cells (LNCaP) and to obtain information on its possi ble mechanism of action. We have shown that melatonin, when given in the na nomolar range, significantly inhibits the proliferation of LNCaP cells; mor eover, the pineal gland hormone affects cell cycle distribution by inducing an accumulation of the cells in G0/G1 and a decrease in S phase. To invest igate the mechanism of action of melatonin, by RT-PCR analysis we were able to demonstrate the expression, in prostate cancer cells, of a mRNA coding for the membrane Mel,, melatonin receptor. However, by radioreceptor assay, no detectable binding of 2-[I-125]iodomelatonin could be observed in membr ane preparations from these cells, suggesting that the levels of translatio n of the mRNA for Mel,, are possibly too low to mediate the antiproliferati ve action of the hormone. This hypothesis is further supported by the follo wing observations: i) melatonin analogs, specifically acting through membra ne receptors (i.e., 2-bromomelatonin), were completely ineffective in modul ating prostate cancer cell proliferation; ii) melatonin failed to prevent f orskolin-induced cAMP accumulation. These results indicate that melatonin, at nanomolar concentrations, exerts a direct antiproliferative action on an drogen-dependent prostate cancer cells, significantly affecting their distr ibution thoughout the cell cycle. Membrane receptors do not seem to be invo lved in the oncostatic action of the pineal gland hormone.