Inhibitions of protein kinase C and proto-oncogene expressions in NIH 3T3 cells by apigenin

Apigenin, a low-toxic and non-mutagenic plant flavonoid, suppresses 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-mediated tumour promotion of mouse skin. TPA has the ability to activate protein kinase C (PKC) and induce proto-oncogene expression. Our study shows that apigenin inhibits PKC by competing with ATP, and exhibits an IC50 value of 10 +/- 0.5 mu M. Apigenin also reduces the level of TPA-stimulated phosphorylation of cellular proteins. Of the protein tyrosine kinases tested, the fibroblast growth factor (FGF) receptor was most strongly affected by apigenin (IC50 20 mu M), and pp60(v-src) most weakly affected (IC50 > 200 mu M). Treatment of NIH 3T3 cells with 100 ng/ml TPA and 10, 50 and 100 mu M apigenin resulted in 50, 80 and 100% suppression of TPA-induced C-JUN expression, respectively. Treatment of TPA with 10 (mu M apigenin inhibited TPA-induced C-FOS expression. TPA-stimulated cell growth was suppressed by 25 mu M apigenin. Our results provide some evidence for understanding apigenin's inhibitory effects of TPA-mediated tumour promotion.