Moreover, we demonstrated that the increased inhibitory effects on COX-2 expression by the combined treatment with fisetin and melatonin was very possibly mediated by promoting p300 and NF-κB translocation from nuclear to cytosol and further inhibiting their binding to COX-2 promoter, thereby abrogating COX-2 transcriptional activation in melanoma cells. The gene discussed is NFKB1; the disease is melanoma.