Metabolomics Reveals the Alteration of Metabolic Pathway by Alpha-Melanocyte-Stimulating Hormone in B16F10 Melanoma Cells

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.

New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma via Comprehensive Bioinformatic Analysis and Validation

“…SKCM is known to be associated with melanogenesis and pigmentation caused by UVB-induced a-MSH/MC1R pathways. a-MSH-stimulating hormones can subsequently alter metabolic pathways and reactions (37). The enrichment results suggested that hub genes selected from these DEGs may play key roles in SKCM and may be therapeutic drug targets and potential prognostic indicators of SKCM.…”

Current Knowledge in Skin Metabolomics: Updates from Literature Review

“…Not surprisingly, the alpha-Melanocyte-Stimulating Hormone (α-MSH) metabolic pathway was found to be altered in melanoma cells [ 90 ]. Previous studies already hypothesized such a pathway to be an interesting therapeutic target and found melaleuca quinquenervia essential oil to efficiently inhibit α-MSH-induced melanin production and oxidative stress in melanoma cell lines [ 30 ].…”

Temporal resolution of melanogenesis determine fatty acid metabolism as key skin pigment regulator

“…Contrary to this, targeting F1F0-ATP synthase that should also result in ROS accumulation, induces hyper-pigmentation 24 . In a recent study, untargeted metabolomics of α-MSH induced B16F10 cells analysed at 1 hour, 24 hours and 48 hours showed minimal changes in the metabolite profile, when compared with their respective controls 25 . While surprising, it is possible that the time points used in this study do not capture the dynamics of metabolite concentrations and metabolic fluxes.…”