title: The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells.
abstract: METHODS
  The tea catechin, (-)-epigallocatechin-3-gallate (EGCG), has potential cancer preventive effects. The prooxidant activity of EGCG may play a role in these effects.
  
  
  RESULTS
  Here, we report that EGCG exerted cytotoxic effects against oral cancer cell lines (IC50 = 83-95 μM). EGCG treatment resulted in formation of extracellular reactive oxygen species (ROS), however, these ROS were rapidly cleared (half-life = 1.7 h). EGCG treatment increased the production of mitochondrial H2 O2 in SCC-25 cells (0-6 h) before the induction of apoptosis. Subsequently, an opening of the mitochondrial transition pore and a decrease in mitochondrial membrane potential were observed. The mitochondria-specific antioxidant, MitoTEMPO, reduced these effects. HGF-1 human gingival fibrobasts were resistant to EGCG (IC50 > 200 μM) and EGCG-induced ROS. EGCG induced differential expression of genes related to antioxidant defense in oral cancer cells and gingival fibroblasts: metallothionein 3, superoxide dismutase 2/3, and thioredoxin reductase 2 were downregulated in SCC-25 cells, but upregulated in HGF-1 cells.
  
  
  CONCLUSIONS
  We conclude that induction of mitochondrial ROS and mitochondrial dysfunction by EGCG play a role in the inhibition of oral cancer, and that gingival fibroblasts are spared from these effects in part because of a selective induction of antioxidant responsive genes.
authors.affiliation: Center of Excellence for Plant and Mushroom Foods for Health, Department of Food Science, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Forester
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Lambert
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013662:Tea / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013662:Tea; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate
keywords: (-)-epigallocatechin-3-gallate; Mitochondria; Oral cancer; Oxidative stress; Tea