title: Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling.
abstract: METHODS
  We have previously reported that the green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), can induce oxidative stress in oral cancer cells but exerts antioxidant effects in normal cells. Here, we report that these differential prooxidative effects are associated with sirtuin 3 (SIRT3), an important mitochondrial redox modulator.
  
  
  RESULTS
  EGCG rapidly induced mitochondria-localized reactive oxygen species in human oral squamous carcinoma cells (SCC-25, SCC-9) and premalignant leukoplakia cells (MSK-Leuk1), but not in normal human gingival fibroblast cells (HGF-1). EGCG suppressed SIRT3 mRNA and protein expression, as well as, SIRT3 activity in SCC-25 cells, whereas it increased SIRT3 activity in HGF-1 cells. EGCG selectively decreased the nuclear localization of the estrogen-related receptor α (ERRα), the transcription factor regulating SIRT3 expression, in SCC-25 cells. This indicates that EGCG may regulate SIRT3 transcription in oral cancer cells via ERRα. EGCG also differentially modulated the mRNA expressions of SIRT3-associated downstream targets including glutathione peroxidase 1 and superoxide dismutase 2 in normal and oral cancer cells.
  
  
  CONCLUSIONS
  SIRT3 represents a novel potential target through which EGCG exerts differential prooxidant effects in cancer and normal cells. Our results provide new biomarkers to be further explored in animal studies.
authors.affiliation: Department of Food Science, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.forename: Jong-Yung
authors.initials: JY
authors.lastname: Park
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Lambert
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria; D009062:Mouth Neoplasms / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D059808:Polyphenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1; D000097983:ERRalpha Estrogen-Related Receptor; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D002392:Catechin; D005979:Glutathione Peroxidase; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D059808:Polyphenols; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D056566:Sirtuin 3; D013482:Superoxide Dismutase; D013662:Tea; D014157:Transcription Factors; D000094765:Glutathione Peroxidase GPX1; D000097983:ERRalpha Estrogen-Related Receptor; D000099156:Superoxide Dismutase 2; C486497:PPARGC1A protein, human; C045651:epigallocatechin gallate; C000722067:GPX1 protein, human
keywords: (-)-Epigallocatechin-3-gallate; Oral cancer; Prooxidant effects; Sirtuin 3; Tea