title: Green tea polyphenol epigallocatechin-3 gallate induces apoptosis of proliferating vascular smooth muscle cells via activation of p53.
abstract: Green tea polyphenols (GTPs), which possess antioxidant properties, have been shown to inhibit the development of atherosclerotic lesions. Epigallocatechin-3-gallate (EGCG), the most abundant GTP, displays antiproliferative effects in a variety of cell types. Here, we examined the effects of GTPs on aortic smooth muscle cell (SMC) proliferation. Treatment with a GTP mixture or EGCG at a dose of 40 to 50 microg/ml slowed SMC growth, while at a higher dose of 80 microg/ml EGCG also induced cell death as judged by TUNEL assay. Apoptosis was mainly observed in proliferating SMCs in subconfluent cultures; whereas at higher confluency, cell viability was largely unaffected. Treatment with 80 microg/ml EGCG induced the tumor suppressor p53, which was functional as judged by activation of the target cyclin-dependent kinase inhibitor p21CIP1. Inhibition of p53 activity with a dominant negative mutant reduced cell death. The increase in p53 protein was due to increased stability. EGCG also induced functional nuclear factor-kappaB (NF-kappaB) complexes, and inhibition of this activity reduced the extent of cell death. Thus, EGCG inhibits growth and induces death of SMCs in a p53- and NF-kappaB-dependent manner. These results provide evidence for a new molecular mechanism whereby green tea polyphenols inhibit SMC proliferation and function to prevent the development of atherosclerosis.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Hofmann
authors.forename: Gail E
authors.initials: GE
authors.lastname: Sonenshein
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015152:Blotting, Northern; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016328:NF-kappa B; D012333:RNA, Messenger; D013662:Tea; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C045651:epigallocatechin gallate