Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma

Abstract

Alpha-melanocyte stimulating hormone (α-MSH) and its receptor, melanocortin 1 receptor (MC1R), have been proposed as potential target for anti-cancer strategies in melanoma research, due to their tissue specific expression and involvement in melanocyte homeostasis. However, their role in prevention and treatment of melanoma is still debated and controversial. Although a large body of evidence supports α-MSH in preventing melanoma development, some preclinical findings suggest that the α-MSH downstream signalling may promote immune escape and cancer resistance to therapy. Additionally, in metastatic melanoma both MC1R and α-MSH have been reported to be overexpressed at levels much higher than normal cells. Furthermore, targeted therapy (e.g. BRAF inhibition in BRAFV600E mutant tumours) has been shown to enhance this phenomenon. Collectively, these data suggest that targeting MC1R could serve as an approach in the treatment of metastatic melanoma. In this review, we explore the molecular biology of α-MSH with particular emphasis into its tumor-related properties, whilst elaborating the experimental evidence currently available regarding the interplay between α-MSH/MC1R axis, melanoma and antitumor strategies.

Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

“…Microphthalmia-transcription factor serves as a key transcription factor responsible for the regulation of melanogenesis by activating the transcription of TYR, TRP-1, and TRP-2. Consequently, the downregulation of MITF and these enzymes leads to a decrease in melanin production [ 62 ]. This investigation aimed to evaluate the ethanolic extract of G. atroviridis fruits on the mRNA expression levels of MITF, TYR, TRP-1, and TRP-2 in α-MSH-stimulated B16F10 cells.…”

Antioxidant and Antimelanogenic Activities of Lactobacillus kunkeei NCHBL-003 Isolated from Honeybees

“…Our study demonstrated that CSK effectively reduced α-MSH-induced melanogenesis in melanocytes without causing cytotoxicity, exhibiting efficacy comparable to arbutin—a recognized skin-lightening agent. Ultraviolet-stimulated ROS in skin cells stimulate α-MSH through MC1R, inducing melanin synthesis [ 61 ]. Our results showed the increased melanin content of melanocytes following α-MSH treatment.…”

The Skin–Brain Axis: From UV and Pigmentation to Behaviour Modulation

“…However, mainly eumelanin is synthesised in the presence of cysteine and sufficient MC1R activity [18]. α-MSH, a paracrine factor secreted by keratinocytes as a result of UVR exposure, binds to MC1R as an agonist and activates adenylyl cyclase [19], ultimately generating a cyclic AMP (cAMP) signalling cascade for the transcription of the MITF and its downstream transcriptional targets, which are enzymes involved in eumelanin synthesis, namely tyrosinase, tyrosinaserelated protein 1, and tyrosinase-related protein 2 (Tyr, TRP1, TRP2) [20]. Based on the review from [8].…”