To define the possible implication of COX-2 in the effects of melatonin action, we analyzed COX-2 protein levels, and observed that DEN increased the expression of this protein, but melatonin supplementation reduced significantly its levels (Fig 5), suggesting a possible role of COX-2 in the apoptotic and ER alteration effects of melatonin in HCC. This evidence concerns the gene PTGS2 and hepatocellular carcinoma.