INHIBITORY EFFECTS OF CURCUMIN ON CARCINOGENESIS IN MOUSE EPIDERMIS

Curcumin (diferuloylmethane) inhibits tumor initiation by benzo[a]pyrene and tumor Promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in female CD-1 mice. ToPical application of curcumin also inhibits benzo[a]pyrene-mediated DNA adduct formation in the epidermis. Co-application Of curcumin with TPA inhibits TPA-induced skin inflammation (mouse ear edema), in epidermal ornithine decarboxylase activity, increased epidermal DNA synthesis, increased epidermal thickness, increased number of epidermal cell layers and leukocyte, infiltration. Curcumin also inhibits arachidonic acid-induced edema of mouse ears in vivo and epidermal cyclooxygenase and lipoxygenase activities in vitro. Curcumin and demethoxycurcumin are equipotent as inhibitors of TPA-induced ear inflammation, and bisdemeihoxycurcumin and tetrahydrocurcumin are less active. The structurally related dietary compounds chlorogenic acid, caffeic acid and ferulic acid are weak antioxidants, weak inhibitors of TPA-induced increases in epidermal ornithine decarboxylase activity, weak inhibitors of TPA-induced mouse ear inflammation, weak inhibitors of cyclooxygenase and lipoxygenase activity, and weak inhibitors of TPA-induced tumor promotion in mouse skin.