HUMAN-MALIGNANT MELANOMA-CELLS EXPRESS HIGH-AFFINITY RECEPTORS FOR MELATONIN - ANTIPROLIFERATIVE EFFECTS OF MELATONIN AND 6-CHLOROMELATONIN

In order to explore the potential oncostatic properties of the pineal hormone, melatonin, we have investigated its binding characteristics a nd functional effects in a human malignant melanoma (M-6) cell line. B inding studies in M-6 membranes showed the coexistence of 2-I-125!iod omelatonin binding sites with picomolar and nanomolar affinities. Guan ine nucleotides caused conversion of all high-affinity sites to a low- affinity state without a change in binding capacity. Melatonin induced a marked concentration-dependent reduction in forskolin-stimulated cA MP accumulation in intact M-6 cells, indicating that it binds to a fun ctional receptor in this cell line. The in vitro proliferation of M-6 cells was significantly inhibited by melatonin and its analogues 6-chl oromelatonin, and 2-iodomelatonin, at concentrations ranging from 10(- 9) to 10(-4) M, as demonstrated by cell counts and measurements of DNA content. These findings indicate that M-6 cells express functional re ceptors for melatonin which may be involved in mediating the antiproli ferative effects of this hormone.