Abstract.
Objective:
To understand the mechanism by which (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, exerts its anti-inflammatory action.
Methods:
To check our hypothesis that the anti-inflammatory properties of EGCG could be related to its antifolate action and whether adenosine and its receptors are involved in EGCG action, we investigated the EGCG-induced suppression of NF-κB in Caco-2 cell monolayer, which acted as a model of the human intestinal epithelium.
Results:
We demonstrate that the anti-inflammatory properties of EGCG are associated with its antifolate activity. By using a natural stable folate we were able to reverse the EGCG suppression of TNF-α-induced NF-κB activation, the phosphorylation and degradation of IκBα and the phosphorylation of Akt in this human colon carcinoma cell line. These suppressions were mediated by the release of adenosine following disruption of the folate cycle by EGCG. By binding to its specific receptors, adenosine can modulate the Akt and NF-κB pathway. Moreover, EGCG produces a significant increase in a specific adenosine receptor, which could explain the suppression of the constitutive activation of NF-κB in colon cancer cells.
Conclusions:
The data suggest that by modulating NF-κB activation, EGCG might not only combat inflammation, but also cancer.
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Abbreviations
- AICAR:
-
aminoimidazole carboxamide ribonucleotide
- APCP:
-
α,β-methylene adenosine-5’-diphosphate
- DHFR:
-
dihydrofolate reductasc
- DMPX:
-
3,7-dimethyl-1- propargylxanthine
- EGCG:
-
(-)-epigallocatechin-3-gallate
- EMSA:
-
electrophoretic mobility shift assay
- FAICAR:
-
formaminoimidazole carboxamide ribonucleotide
- FCS:
-
fetal calf serum
- FGAR:
-
formylglycinamide ribonucleotide
- GAR:
-
glycinamide ribonucleotide
- Leucovorin:
-
5-formyltetrahydrofolate
- MTX:
-
methotrexate
- NF-κB:
-
nuclear factor kappa B
- THF:
-
tetrahydrofolate
- TMP:
-
trimethoprim
- TNF-α:
-
tumor necrosis factor-α.
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Received 18 January 2008; returned for revision 18 March 2008; received from final revision 1 April 2008; accepted by I. Ahnfelt-Rønne 25 April 2008
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Navarro-Perán, E., Cabezas-Herrera, J., Sánchez-del-Campo, L. et al. The anti-inflammatory and anti-cancer properties of epigallocatechin-3-gallate are mediated by folate cycle disruption, adenosine release and NF-κB suppression. Inflamm. res. 57, 472–478 (2008). https://doi.org/10.1007/s00011-008-8013-x
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DOI: https://doi.org/10.1007/s00011-008-8013-x