Our findings revealed that treatment of A375.S2 melanoma cells with cudraflavone C induced the activation and phosphorylation of MAPKs (p38, ERK, and JNK); however, these effects were suppressed by pre-treating the cells with specific MAPK inhibitors (SB-202190, U-0126, SP600125), or by a mitochondria-targeted antioxidant (MitoTEMPOL). This evidence concerns the gene MAPK8 and melanoma.