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The role of sirtuin 3 in the differential pro‐oxidant effects of (‐)‐epigallocatechin‐3‐gallate in oral cells (261.4)
Author(s) -
Tao Ling,
Lambert Joshua
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.261.4
Subject(s) - sirt3 , sirtuin , apoptosis , chemistry , cancer cell , cancer research , epigallocatechin gallate , cancer , pharmacology , antioxidant , medicine , microbiology and biotechnology , endocrinology , biochemistry , biology , acetylation , polyphenol , gene
Dietary approaches may play an important role in reducing oral cancer burden. The green tea catechin, (‐)‐epigallocatechin‐3‐gallate (EGCG), has been reported to have cancer preventive effects. Previously, we found that EGCG induced mitochondrial dysfunction, oxidative stress and apoptosis in oral cancer cells but exerted antioxidant effects in normal oral cells. In this study, we aim to investigate the role of sirtuin 3 (SIRT3), an important mitochondrial redox balance regulator, in EGCG‐induced differential pro‐oxidant effects in oral cells. We found 100 µM EGCG significantly decreased SIRT3 mRNA (15%‐56%; 1‐12 h) and protein levels (17%‐34%; 6‐24 h), as well as, activity (58%; 12 h) in SCC‐25 oral squamous carcinoma cells. By comparison, there was no significant effect of EGCG on SIRT3 mRNA and protein levels, but a remarkable increase of SIRT3 activity (7.5‐fold; 12 h) in HGF‐1 human gingival fibroblast cells. The estrogen‐related receptor alpha (ERRα) regulates transcription of SIRT3. EGCG significantly decreased the mRNA (20%‐44%; 3‐6 h) and protein levels (31%‐50%; 6‐24 h) of ERRα in SCC‐25 but not HGF‐1 cells, indicating that EGCG regulates SIRT3 expression through modulation of ERRα. The effect of EGCG on transcription activity of ERRα is under investigation. This study identified SIRT3 as a novel target of EGCG, thus providing additional mechanistic information for future in vivo studies. Grant Funding Source : Supported by a grant from the American Institute for Cancer Research (Grant #10A102 to JDL)