INHIBITORY EFFECT OF CURCUMIN ON XANTHINE DEHYDROGENASE OXIDASE INDUCED BY PHORBOL-12-MYRISTATE-13-ACETATE IN NIH3T3 CELLS/

Treatment of NIH3T3 cells with the tumor promoter phorbol-12-myristate -13-acetate (PMA) results within 30 min in a 1.8-fold elevation of xan thine oxidase (XO) activity, an enzyme capable of generating reactive oxygen species such as superoxide and hydrogen peroxide. Simultaneous administration of 2 and 10 mu M curcumin with 100 ng/ml PMA inhibits P MA-induced increases in XO activity measured 30 min later by 22.7% aci d 36.5%, respectively. The PMA-induced conversion of xanthine dehydrog enase (XD) to XO is reduced by curcumin to the basal level noted in un treated cells. Activity of XO is remarkably inhibited by curcumin in v itro, but not by its structurally related compounds caffeic acid, chlo rogenic acid and ferulic acid. Based on these findings, induction of X O activity is deemed to be one of the major causative elements in PMA- mediated tumor promotion, and the major inhibitory mechanism of curcum in on PMA-induced increases in XD/XO enzyme activities is through dire ct inactivation at the protein level.