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 and functional effects in a human malignant melanoma (M-6) cell line. Binding studies in M-6 membranes showed the coexistence of 2-[125I]iodomelatonin binding sites with picomolar and nanomolar affinities. Guanine 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 cAMP accumulation in intact M-6 cells, indicating that it binds to a functional receptor in this cell line. The in vitro proliferation of M-6 cells was significantly inhibited by melatonin and its analogues 6-chloromelatonin, 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 receptors for melatonin which may be involved in mediating the antiproliferative effects of this hormone.
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
S W
SW
Ying
L P
LP
Niles
C
C
Crocker
D000067956:Adenylyl Cyclase Inhibitors; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008545:Melanoma / Q000378:metabolism*; D008550:Melatonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D004273:DNA, Neoplasm; D007211:Indoles; D007457:Iodine Radioisotopes; D009711:Nucleotides; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; D005576:Colforsin; C024100:6-chloromelatonin; C044556:2-iodomelatonin; D000242:Cyclic AMP; D008550:Melatonin