INHIBITORY EFFECTS OF ASCORBIC-ACID ON AP-1 ACTIVITY AND TRANSFORMATION OF JB6 CELLS

Ascorbic acid (vitamin C) has been reported as an anti-cancer agent. P revious in vitro studies using either primary cell cultures from cance r patients or tumor cell lines have indicated that different kinds of tumor cells may have different sensitivities to ascorbic acid for the inhibition of tumorigeneity or growth. Because the JB6 mouse epidermal cell system has been used extensively as an in vitro model for the st udy of tumor promotion and progression, we assessed the effects of asc orbic acid on transformation in JB6 cell variants. The results show th at ascorbic acid could inhibit 5.5% to 97.1% of transformation of JB6 P+ cell Cl 41-19 induced by TPA, EGF or EGF + insulin, but has no effe ct on anchorage-independent growth of JB6 transformed cell A33. Since our previous results indicated that induced AP-1 activity is required for tumor promoter induced-transformation, we tested whether inhibitio n of tumor promoter-induced transformation by ascorbic acid is through an AP-1 inhibition mechanism. Our results indicated that ascorbic aci d inhibited AP-I activity at the same dose range for inhibition of tra nsformation. These results demonstrated that ascorbic acid has inhibit ory effects on JB6 cell tumor promoter-induced transformation, but no influence on tumor cell phenotype expression and provided the basic kn owledge for understanding of vitamin C action on tumor prevention.