ARP101 inhibits α-MSH-stimulated melanogenesis by regulation of autophagy in melanocytes

•ARP101 inhibits α-MSH-stimulated melanogenesis in melanocytes.•ARP101 efficiently induces autophagy in melanocytes.•Autophagy inhibition attenuates anti-melanogenic activity of ARP101.•Thus, ARP101 inhibits α-MSH-stimulated melanogenesis through activation of autophagy in melanocytes.

Autophagy is a cooperative process between autophagosomes and lysosomes that degrades cellular organelles. Although autophagy regulates the turnover of cellular components, its role in melanogenesis is not clearly established. Previously, we reported that ARP101 induces autophagy in various cancer cells. Here, we show that ARP101 inhibits melanogenesis by regulation of autophagy. ARP101 inhibited α-MSH-stimulated melanin synthesis and suppressed the expression of tyrosinase and TRP1 in immortalized mouse melanocytes. ARP101 also induced autophagy in melanocytes. Knockdown of ATG5 reduced both anti-melanogenic activity and autophagy mediated by ARP101 in α-MSH treated melanocytes. Electron microscopy analysis further revealed that autophagosomes engulf melanin or melanosome in α-MSH and ARP101-treated cells. Collectively, our results suggest that ARP101 inhibits α-MSH-stimulated melanogenesis through the activation of autophagy in melanocytes.