The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (–)-epigallocatechin-3-gallate, in oral cells
Article first published online: 18 NOV 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 4, pages 665–676, April 2014
How to Cite
Tao, L., Forester, S. C. and Lambert, J. D. (2014), The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (–)-epigallocatechin-3-gallate, in oral cells. Mol. Nutr. Food Res., 58: 665–676. doi: 10.1002/mnfr.201300427
- Issue published online: 1 APR 2014
- Article first published online: 18 NOV 2013
- Manuscript Accepted: 28 AUG 2013
- Manuscript Revised: 26 AUG 2013
- Manuscript Received: 12 JUN 2013
- The American Institute for Cancer Research
- Oral cancer;
- Oxidative stress;
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.
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.