Epigallocatechin-3-gallate enhances ischemia/reperfusion-induced apoptosis in human umbilical vein endothelial cells via AKT and MAPK pathways
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Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to promote apoptosis in cancer cells. However, the role of EGCG in endothelial cells following ischemia/reperfusion (I/R) injury remains unclear. In the present study, we investigated the mechanisms by which EGCG enhances I/R-induced cell growth inhibition and apoptosis in human umbilical vein endothelial cells (HUVECs). Our results showed that EGCG treatment caused cell proliferation inhibition during I/R injury, and this effect was associated with increased p27 and p21 levels and reduced cyclin D1 level. Moreover, treatment of cells with EGCG resulted in increase of caspase-3 and Bax and decrease of Bcl-2, enhancing I/R-induced apoptosis. Interestingly, EGCG decreased I/R-induced phosphorylation of AKT and its downstream substrates Foxo1 and Foxo3a and ERK1/2. In contrast, EGCG increased JNK1/2 and c-Jun phosphorylation. Furthermore, both wortamannin (PI3K inhibitor) and U0126 (MEK1/2 inhibitor) markedly enhanced EGCG-induced apoptosis during I/R, whereas SP600125 (JNK inhibitor) attenuated the action of EGCG. Taken together, our study for the first time suggest that EGCG is able to enhance growth arrest and apoptosis of HUVECs during I/R injury, at least in part, through inhibition of AKT and ERK1/2 and activation of JNK1/2 signaling pathways.
KeywordsEpigallocatechin-3-gallate Ischemia-reperfusion Human umbilical vein endothelial cells Apoptosis AKT Mitogen-activated protein kinases
This work was supported by grants from China Natural Science Foundation (H. L., 2006CB910306) and the 111 project (H. L., B08007).
The authors declare that they have no conflict of interest.
- 9.Chen L, Zhang HY (2007) Cancer preventive mechanisms of the green tea polyphenol (-)-epigallocatechin-3-gallate. Molecules (Basel, Switzerland) 12:946–957Google Scholar
- 10.Park G, Yoon BS, Moon JH, Kim B, Jun EK, Oh S, Kim H, Song HJ, Noh JY, Oh C, You S (2008) Green tea polyphenol epigallocatechin-3-gallate suppresses collagen production and proliferation in keloid fibroblasts via inhibition of the STAT3-signaling pathway. J Invest Dermatol 128:2429–2441PubMedCrossRefGoogle Scholar
- 13.Ahn HY, Hadizadeh KR, Seul C, Yun YP, Vetter H, Sachinidis A (1999) Epigallocathechin-3 gallate selectively inhibits the PDGF-BB-induced intracellular signaling transduction pathway in vascular smooth muscle cells and inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells (A172). Mol Biol Cell 10:1093–1104PubMedGoogle Scholar
- 15.Kim JA, Formoso G, Li Y, Potenza MA, Marasciulo FL, Montagnani M, Quon MJ (2007) Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J Biol Chem 282:13736–13745PubMedCrossRefGoogle Scholar
- 32.Ferrandi C, Ballerio R, Gaillard P, Giachetti C, Carboni S, Vitte PA, Gotteland JP, Cirillo R (2004) Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats. Br J Pharmacol 142:953–960PubMedCrossRefGoogle Scholar