Berberine Chloride Suppresses Melanogenesis in B16-F1 Melanoma Cells in Association with ERK and Autophagy-Related Signaling

Skin pigmentation is regulated by intrinsic and extrinsic factors and is closely associated with melanogenesis and cellular homeostasis. Autophagy is a cellular self-digestion process that contributes to homeostatic regulation, but its role in melanogenesis remains to be further clarified. This study investigated whether berberine chloride (BBC), an isoquinoline alkaloid, modulates melanin production through autophagy-related signaling in B16-F1 melanoma cells. Tyrosinase activity was examined by tyrosinase zymography, extracellular melanin levels in the culture supernatant were measured after BBC treatment, and the expression of melanogenesis-, mitogen-activated protein kinase (MAPK)-, and autophagy-related proteins was analyzed by Western blotting. BBC inhibited tyrosinase activity and reduced extracellular melanin levels in a dose-dependent manner. BBC also increased phosphorylated extracellular signal-regulated kinase (p-ERK) levels while decreasing melanogenesis-related protein expression. In addition, BBC modulated MAPK signaling and the expression of autophagy-associated proteins. Small interfering RNA-mediated knockdown of Atg5, Beclin1, or ERK partially restored extracellular melanin levels in BBC-treated cells. These findings suggest that BBC suppresses melanogenesis in B16-F1 melanoma cells in association with ERK and autophagy-related signaling.