Abstract

The purpose of this study was to understand the changes of metabolic pathway induced by alpha-melanocyte-stimulating hormone (α-MSH) in B16F10 melanoma cells in an untargeted metabolomics approach. Cells were treated with 100 nM of α-MSH and then incubated for 48 h. α-MSH increased tyrosinase activity and melanin content by 56.5 and 61.7%, respectively, compared to untreated cells after 48 h of cultivation. The clear separation between groups was observed in the principal component analysis score plot, indicating that the levels of metabolites of melanoma cells were altered by treatment with α-MSH. Metabolic pathways affected by α-MSH were involved in some amino acid metabolisms. The increased levels of fumaric acid, malic acid, oxaloacetic acid and citric acid related to the citric acid cycle pathway after α-MSH treatment suggested enhanced energy metabolism. Metabolic pathways altered by α-MSH treatment can provide useful information to develop new skin pigmentation inhibitors or anti-obesity drugs.

Highlights

  • Melanogenesis can be stimulated by the ultraviolet or visible light-induced alpha-melanocyte-stimulating hormone (α-MSH) in melanocytes [1]

  • The Principal component analysis (PCA) score plot at 24 h showed clear differentiation, suggesting that the metabolites of melanoma cells can be altered by treatment with α-MSH

  • Α-MSH increased tyrosinase activity and melanin content by 56.5% and 61.7%, respectively, compared to untreated cells at 48 h (Figure S1)

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Summary

Introduction

Melanogenesis can be stimulated by the ultraviolet or visible light-induced alpha-melanocyte-stimulating hormone (α-MSH) in melanocytes [1]. While α-MSH, an endogenous peptide hormone and neuropeptide of the melanocortin family, is well known for its physiological function of stimulation of melanin production, it plays an important role in controlling appetite and energy balance [2], sexual activity [3] and ischemia and reperfusion-associated injury [4]. Several studies have shown that α-MSH can reduce UV-induced skin damage through inositol trisphosphate (IP3 ) kinase-Akt pathway [7] and nucleotide excision repair [8]. Potential strategies have been proposed to prevent skin cancer by improving pigmentation with α-MSH analogs [9] or cAMP agonists [10]. An important concern about α-MSH is its overproduction causing various skin diseases, such as chloasma, freckles and skin cancer [11]

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