The anti-inflammatory and anti-cancer properties of epigallocatechin-3-gallate are mediated by folate cycle disruption, adenosine release and NF-kappaB suppression.
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-kappaB 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-alpha-induced NF-kappaB activation, the phosphorylation and degradation of IkappaBalpha 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-kappaB pathway. Moreover, EGCG produces a significant increase in a specific adenosine receptor, which could explain the suppression of the constitutive activation of NF-kappaB in colon cancer cells.


CONCLUSIONS
The data suggest that by modulating NF-kappaB activation, EGCG might not only combat inflammation, but also cancer.
Navarro-Perán
E
E
Departamento de Bioquímica y Biología Molecular A, Facultad de Biología, Universidad de Murcia, E-30100, Espinardo, Murcia, Spain.
Cabezas-Herrera
J
J
Sánchez-Del-Campo
L
L
García-Cánovas
F
F
Rodríguez-López
J N
JN
D000241:Adenosine / Q000378:metabolism*; D016588:Anticarcinogenic Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D018938:Caco-2 Cells; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D002955:Leucovorin / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014803:Vitamin B Complex / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D014803:Vitamin B Complex; D000072000:NF-KappaB Inhibitor alpha; D002392:Catechin; D005492:Folic Acid; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt; D000241:Adenosine; D002955:Leucovorin