Caffeic acid phenethyl ester inhibits proliferation and migration, and induces apoptosis in platelet-derived growth factor-BB-stimulated human coronary smooth muscle cells.

BACKGROUND/AIMS Restenosis after a percutaneous coronary intervention (PCI) during treatment for coronary artery disease is closely related to smooth muscle cell (SMC) proliferation and migration. In this study, we investigated the effects of caffeic acid phenethyl ester (CAPE) and its underlying mechanism on human coronary SMCs (HCSMCs) after platelet-derived growth factor-BB (PDGF-BB) stimulation in vitro. METHODS AND RESULTS The results showed that CAPE inhibited proliferation and migration, and induced apoptosis. Concomitantly, CAPE inhibited activation of AKT1, MEK1 and ERK1/2 signaling molecules at 10-60 min after CAPE treatment. As revealed by flow cytometry, DNA fragmentation and TUNEL assay, the cells accumulated at the sub-G(1) phase, and cell apoptosis was observed after 30 and 90 μM CAPE treatment for 72 h. CAPE triggered the release of cytochrome c from mitochondria to cytosol, upregulated the proapoptotic gene Bax and downregulated the antiapoptotic gene Bcl-2. Upregulation of caspase-9 and caspase-3 indicated that CAPE precipitated the mitochondrion-dependent apoptotic signaling pathway. CONCLUSIONS These results provide a molecular explanation for the antiproliferation, antimigration and proapoptotic effects of CAPE on HCSMCs after PDGF-BB stimulation.