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
Version of Record online: 17 NOV 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 59, Issue 2, pages 203–211, February 2015
How to Cite
Tao, L., Park, J.-Y. and Lambert, J. D. (2015), 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. Mol. Nutr. Food Res., 59: 203–211. doi: 10.1002/mnfr.201400485
- Issue online: 2 FEB 2015
- Version of Record online: 17 NOV 2014
- Accepted manuscript online: 20 OCT 2014 04:34AM EST
- Manuscript Accepted: 27 SEP 2014
- Manuscript Revised: 23 SEP 2014
- Manuscript Received: 18 JUL 2014
- American Institute for Cancer Research. Grant Number: #10A102
- Pennsylvania State University College of Agricultural Sciences
- Oral cancer;
- Prooxidant effects;
- Sirtuin 3;
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.
Methods and 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.
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.