title: Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines.
abstract: Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10(-12)-10(-3) M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor RORalpha by RT-PCR. Melatonin at pharmacological concentrations (10(-3)-10(-7) M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10(-12)-10(-10) M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor RORalpha including its isoform RORalpha4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, 38163, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Fischer
authors.forename: M A
authors.initials: MA
authors.lastname: Zmijewski
authors.forename: B
authors.initials: B
authors.lastname: Zbytek
authors.forename: T W
authors.initials: TW
authors.lastname: Sweatman
authors.forename: R M
authors.initials: RM
authors.lastname: Slominski
authors.forename: J
authors.initials: J
authors.lastname: Wortsman
authors.forename: A
authors.initials: A
authors.lastname: Slominski
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free; D003600:Cytosol / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D011808:Quinone Reductases / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D016895:Culture Media, Serum-Free; D016166:Free Radical Scavengers; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D015534:Trans-Activators; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D008550:Melatonin