Tumor-secreted Autocrine Motility Factor: Pro-melanogenic Activity at Low Doses and Reversal Effect at Higher Doses Combined With Glycyrrhetinic Acid

Background/Aim: Skin darkening can result from various factors, with prolonged sun exposure being a primary cause. α-Melanocyte-stimulating hormone (α-MSH) plays a crucial role in stimulating melanin production. However, our understanding of hyperpigmentation in individuals with cancer or rheumatoid arthritis (RA) remains limited. This study investigated the effect of autocrine motility factor (AMF) on hyperpigmentation. Materials and Methods: The effect of AMF on melanogenesis was examined in B16F10 mouse melanoma cells through growth assays, quantitative PCR, western blot analysis, and tyrosinase activity assays. Effects of glycyrrhetinic acid (GA) alone and in combination with AMF were also evaluated. Results: At lower doses, AMF promoted melanogenesis by upregulating melanogenesis-related genes, with efficacy comparable to that of α-MSH. Higher doses of AMF significantly suppressed melanogenesis, accompanied by decreased B16F10 cell growth. GA inhibited melanin production, and its co-administration with AMF showed synergy. Additionally, GA counteracted the AMF-induced increase in melanin production. Conclusion: AMF may play a role in pathological condition-related skin darkening, and GA represents a potential agent for regulating hyperpigmentation when combined with AMF.