Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Abstract

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 ROR· 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 ROR· including its isoform ROR·4 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.

20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells

“…The assay followed standard methodology used in our laboratory as described previously (18,29,76 control) were added with media being changed every 3 days. After 7 days of incubation, the colonies were fixed and then stained with 2% crystal violet, and the number and size of the colonies were measured using an ARTEK counter 880 (Dynex Technologies, Chantilly, VA).…”

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

“…In addition, several clinical studies have reported positive results with melatonin in patients with metastatic malignant melanoma. Most recently, melatonin has been shown to have tumorostatic effect in human melanoma cell lines of different behavior [65]. The intensity of the oncostatic response to melatonin was related to the cell-line -specific pattern of melatonin cell surface and nuclear receptor expressions [65].…”

“…Most recently, melatonin has been shown to have tumorostatic effect in human melanoma cell lines of different behavior [65]. The intensity of the oncostatic response to melatonin was related to the cell-line -specific pattern of melatonin cell surface and nuclear receptor expressions [65]. Thus, targeting melatonin receptors may represent a realistic approach in melanoma therapy [42].…”

“…Because melatonin receptors are expressed in melanocytes and melanoma cells, these have the potential to mediate phenotypic actions on cellular proliferation and differentiation [16,42,43,64]. In addition, its receptor-independent activity suggests that melatonin could also have a protective role against UV-induced pathology [42,43,65]. Both biosynthetic and biodegradative pathways for melatonin have been initially characterized in whole human skin and in melanoma cells [42,43,66,67].…”

Transcriptomic Analysis of Melanoma Cells Extracted From Different Sites of the Primary Tumor

“…Besides, melatonin in pharmacological concentrations suppresses proliferation of the melanoma cells [18].…”