title: Preventive effects of epigallocatechin-3-O-gallate against replicative senescence associated with p53 acetylation in human dermal fibroblasts.
abstract: Considering the various pharmacological activities of epigallocatechin-3-O-gallate (EGCG) including anticancer, and anti-inflammatory, antidiabetic, and so forth, relatively less attention has been paid to the antiaging effect of EGCG on primary cells. In this study, the preventive effects of EGCG against serial passage-induced senescence were investigated in primary cells including rat vascular smooth muscle cells (RVSMCs), human dermal fibroblasts (HDFs), and human articular chondrocytes (HACs). The involvement of Sirt1 and acetylated p53 was examined as an underlying mechanism for the senescence preventive activity of EGCG in HDFs. All cells were employed with the initial passage number (PN) between 3 and 7. For inducing senescence, the cells were serially passaged at the predetermined times and intervals in the absence or presence of EGCG (50 or 100 μM). Serial passage-induced senescence in RVSMCs and HACs was able to be significantly prevented at 50 μM EGCG, while in HDFs, 100 μM EGCG could significantly prevent senescence and recover their cell cycle progression close to the normal level. Furthermore, EGCG was found to prevent serial passage- and H(2)O(2)-induced senescence in HDFs by suppressing p53 acetylation, but the Sirt1 activity was unaffected. In addition, proliferating HDFs showed similar cellular uptake of FITC-conjugated EGCG into the cytoplasm with their senescent counterparts but different nuclear translocation of it from them, which would partly account for the differential responses to EGCG in proliferating versus senescent cells. Taking these results into consideration, it is suggested that EGCG may be exploited to craft strategies for the development of an antiaging or age-delaying agent.
authors.affiliation: Department of Applied Nanoscience and BK 21 Nano Fusion Technology Division, College of Nanoscience & Nanotechnology, Pusan National University, Busan, Republic of Korea. nanohan@pusan.ac.kr
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Han
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Bongju
authors.initials: B
authors.lastname: Kim
authors.forename: Jun Jae
authors.initials: JJ
authors.lastname: Lee
authors.forename: Suong-Hyu
authors.initials: SH
authors.lastname: Hyon
authors.forename: Jong-Chul
authors.initials: JC
authors.lastname: Park
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008856:Microscopy, Fluorescence; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D056564:Sirtuin 1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D020011:Protective Agents; D016159:Tumor Suppressor Protein p53; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D001616:beta-Galactosidase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D016650:Fluorescein-5-isothiocyanate