The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells

Ling Tao, Sarah C. Forester, Joshua D. Lambert

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41 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)665-676
Number of pages12
JournalMolecular Nutrition and Food Research
Volume58
Issue number4
DOIs
StatePublished - Jan 1 2014

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Catechin
epigallocatechin
green tea
Tea
catechin
cytotoxicity
mouth
Oxidative Stress
oxidative stress
reactive oxygen species
Mouth Neoplasms
Reactive Oxygen Species
cells
Antioxidants
Thioredoxin Reductase 2
Inhibitory Concentration 50
fibroblasts
inhibitory concentration 50
Fibroblasts
antioxidants

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

Cite this

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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.",
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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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