When 4′-O-methylfisetin was added into the culture medium of B16F10 melanoma cells, the SIK2-mediated suppression of CREB activity was weakened (Figure 4B) and melanogenesis was strongly promoted (Figure 4C), suggesting that eumelanogenesis in fisetin-treated mice might be induced by 4′-O-methylfisetin. The gene discussed is CREB1; the disease is melanoma.