5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone prevented 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced extracellular regulated protein kinases 1/2 (ERK1/2), p38 mitogen-activated protein kinases (p38MAPK) and phosphorylated-protein kinase B (p-Akt), and iNOS activities and COX-2 expression in mouse skin, which further blocked tumor formation by reducing the tumor incidence and tumor multiplicity of papillomas [30]. Here, PTGS2 is linked to papilloma.