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

作者：Tao Ling; Park Jong Yung; Lambert Joshua D^*

来源：Molecular Nutrition & Food Research, 2015, 59(2): 203-211.

DOI：10.1002/mnfr.201400485

• (-)-Epigallocatechin-3-gallate
• Oral cancer
• Prooxidant effects
• Sirtuin 3
• Tea

Scope: 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 alpha (ERR alpha), the transcription factor regulating SIRT3 expression, in SCC-25 cells. This indicates that EGCG may regulate SIRT3 transcription in oral cancer cells via ERR alpha. 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.
Conclusion: 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.

• 出版日期2015-2