Resveratrol Inhibits Alpha-Melanocyte-Stimulating Hormone Signaling, Viability, and Invasiveness in Melanoma Cells

Abstract

Melanoma is a malignancy with high potential to invasion and treatment resistance. Theα-melanocyte-stimulating hormone (α-MSH) signal transduction involving Wnt/β-catenin, c-Kit, and microphthalmia-associated transcription factor (MITF), a known pathway to produce melanin, has been demonstrated as one of cancer stem cell characteristics. This study was aimed to examine the effect of resveratrol, an abundant ingredient of grape and medicinal plants, onα-MSH signaling, viability, and invasiveness in melanoma cells. Byα-MSH treatment, the melanin production in B16 melanoma cells was augmented as a validation for activation ofα-MSH signaling. The upregulated expression ofα-MSH signaling-related moleculesβ-catenin, c-Kit, and MITF was suppressed by resveratrol and/or STI571 treatment. Nuclear translocation of MITF, a hallmark ofα-MSH signaling activation, was inhibited by combined treatment of resveratrol and STI571. At effective concentration, resveratrol and/or STI571 inhibited cell viability andα-MSH-activated matrix metalloproteinase- (MMP-)9 expression and invasion capacity of B16 melanoma cells. In conclusion, resveratrol enhances STI571 effect on suppressing theα-MSH signaling, viability, and invasiveness in melanoma cells. It implicates that resveratrol may have potential to modulate the cancer stem cell characteristics of melanoma.