Epigallocatechin-3-gallate inhibits basic fibroblast growth factor-induced intracellular signaling transduction pathway in rat aortic smooth muscle cells

Daily green tea drinking showed preventive effects on the progression of atherosclerosis. Although epigallocatechin-3-gallate [EGCG] has anti-proliferative effects on various cells, relatively little is known about the molecular mechanisms of the anti-proliferative effects of EGCG. To determine whether the transduction signals and protooncogene expression were affected by EGCG, this study investigated the molecular mechanism of the anti-proliferative effects in basic fibroblast growth factor (bFGF)-stimulated rat aortic smooth muscle cells (RAoSMCs). EGCG inhibited the proliferative response stimulated by 10% fetal bovine serum dose dependently in RAoSMCs (median inhibitory concentration [IC₅₀]: 28.4 × 10^-6 M). EGCG also inhibited the migration of bFGF-stimulated RAoSMCs in a dose-dependent manner, showing that 21.8 × 10^-6 M of EGCG significantly inhibited the migration by 75 ± 5% in comparison with bFGF-stimulated migration. In RAoSMCs, EGCG dramatically inhibited Ras activation and c-jun N-terminal kinase (JNK) activity without affecting protein kinase C expression. Induction of c-jun mRNA stimulated by bFGF was significantly reduced dose dependently up to 87.3 × 10^-6 M of EGCG. These results indicate that the anti-proliferative effect of EGCG on RAoSMCs is partly Ras/JNK mediated, independent of protein kinase C, and is attributable to the downregulation of c-jun expression.