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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 665-676 |
| Number of pages | 12 |
| Journal | Molecular Nutrition and Food Research |
| Volume | 58 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 1 2014 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Food Science
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The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells. / Tao, Ling; Forester, Sarah C.; Lambert, Joshua D.
In: Molecular Nutrition and Food Research, Vol. 58, No. 4, 01.01.2014, p. 665-676.Research output: Contribution to journal › Article
TY - JOUR
T1 - The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells
AU - Tao, Ling
AU - Forester, Sarah C.
AU - Lambert, Joshua D.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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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U2 - 10.1002/mnfr.201300427
DO - 10.1002/mnfr.201300427
M3 - Article
C2 - 24249144
AN - SCOPUS:84897061881
VL - 58
SP - 665
EP - 676
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
SN - 1613-4125
IS - 4
ER -