The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (–)-epigallocatechin-3-gallate, in oral cells

Authors

  • Ling Tao,

    1. Center of Excellence for Plant and Mushroom Foods for Health, Department of Food Science, The Pennsylvania State University, University Park, PA, USA
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  • Sarah C. Forester,

    1. Center of Excellence for Plant and Mushroom Foods for Health, Department of Food Science, The Pennsylvania State University, University Park, PA, USA
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  • Joshua D. Lambert

    Corresponding author
    1. Center of Excellence for Plant and Mushroom Foods for Health, Department of Food Science, The Pennsylvania State University, University Park, PA, USA
    • Correspondence: Dr. Joshua D. Lambert, Department of Food Science, Pennsylvania State University, 332 Food Science Building, University Park, PA 16802, USA

      E-mail: jdl134@psu.edu

      Fax: +1-814-863-6132

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Abstract

Scope

The tea catechin, (–)-epigallocatechin-3-gallate (EGCG), has potential cancer preventive effects. The prooxidant activity of EGCG may play a role in these effects.

Methods and 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 H2O2 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.

Conclusion

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.

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