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. Previous in vitro studies using either primary cell cultures from cancer 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 study of tumor promotion and progression, we assessed the effects of ascorbic acid on transformation in JB6 cell variants. The results show that 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 effect 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 inhibition of tumor promoter-induced transformation by ascorbic acid is through an AP-1 inhibition mechanism. Our results indicated that ascorbic acid inhibited AP-1 activity at the same dose range for inhibition of transformation. These results demonstrated that ascorbic acid has inhibitory effects on JB6 cell tumor promoter-induced transformation, but no influence on tumor cell phenotype expression and provided the basic knowledge for understanding of vitamin C action on tumor prevention.