Premium
The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (–)‐epigallocatechin‐3‐gallate, in oral cells
Author(s) -
Tao Ling,
Forester Sarah C.,
Lambert Joshua D.
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300427
Subject(s) - reactive oxygen species , chemistry , mitochondrial ros , oxidative stress , mitochondrion , antioxidant , catechin , cancer cell , thioredoxin reductase , apoptosis , superoxide dismutase , epigallocatechin gallate , biochemistry , microbiology and biotechnology , pharmacology , thioredoxin , biology , cancer , polyphenol , genetics
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 (IC 50 = 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 H 2 O 2 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 (IC 50 > 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.