Human malignant melanoma cells express high-affinity receptors for melatonin: antiproliferative effects of melatonin and 6-chloromelatonin

Eur J Pharmacol. 1993 Jul 15;246(2):89-96. doi: 10.1016/0922-4106(93)90084-m.

Abstract

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.

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Cell Division / drug effects
  • Cell Membrane / metabolism
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • DNA, Neoplasm / biosynthesis
  • Humans
  • Indoles / pharmacology
  • Iodine Radioisotopes
  • Kinetics
  • Melanoma / metabolism*
  • Melatonin / analogs & derivatives*
  • Melatonin / pharmacology
  • Nucleotides / pharmacology
  • Receptors, Melatonin
  • Receptors, Neurotransmitter / biosynthesis*
  • Receptors, Neurotransmitter / metabolism
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism

Substances

  • Adenylyl Cyclase Inhibitors
  • DNA, Neoplasm
  • Indoles
  • Iodine Radioisotopes
  • Nucleotides
  • Receptors, Melatonin
  • Receptors, Neurotransmitter
  • Colforsin
  • 6-chloromelatonin
  • 2-iodomelatonin
  • Cyclic AMP
  • Melatonin