TitleResponse of Apc(min) and A33 (delta N beta-cat) mutant mice to treatment with tea, sulindac, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
Publication TypeJournal Article
Year of Publication2002
AuthorsOrner GA, Dashwood W-M, Blum CA, G Díaz D, Li Q, Al-Fageeh M, Tebbutt N, Heath JK, Ernst M, Dashwood RH
JournalMutat Res
Date Published2002 Sep 30
KeywordsAdenomatous Polyposis Coli Protein, Animals, Anti-Inflammatory Agents, Non-Steroidal, beta Catenin, Catechin, Cell Line, Cytoskeletal Proteins, Drug Combinations, Imidazoles, Intestinal Mucosa, Intestinal Neoplasms, Luciferases, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Plant Extracts, Polyps, Sulindac, Tea, Trans-Activators

There is growing interest in the potential health benefits of tea, and a recent report described the potent antimutagenic activity of white tea in comparison with green tea against several heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) [Mutat. Res. 495 (2001) 61]. We compared the inhibitory effects of white and green teas with sulindac, a nonsteroidal anti-inflammatory agent, in two different mouse models of intestinal tumorigenesis. In the Apc(min) mouse, white and green teas given at human-relevant concentrations (1.5% w/v, 2-min brew), and sulindac (80 ppm in the drinking water), each suppressed polyp formation by approximately 50%, and the combination of white tea plus sulindac was more effective than either treatment alone (P=0.05). Mice expressing an N-terminally truncated, oncogenic version of beta-catenin (A 33(delta N beta-cat) mutant mice) developed colonic aberrant crypt foci (ACF) spontaneously, but PhIP treatment increased the incidence and number of ACF per colon. In the normal-looking intestinal mucosa of Apc(min) and A 33(delta N beta-cat) mice, white tea plus sulindac treatment markedly attenuated the expression of beta-catenin protein, and this was recapitulated in vitro in cells transiently transfected with beta-catenin plus Tcf-4 and treated with tea or the major tea polyphenol epigallocatechin-3-gallate (EGCG). Expression of a beta-catenin/Tcf reporter was inhibited by EGCG in the transfected cells, and the beta-catenin/Tcf target genes cyclin D1 and c-jun were downregulated in vivo by tea plus sulindac treatment. Collectively, the data support a chemopreventive role for tea and sulindac against intermediate and late stages of colon cancer, via effects on the beta-catenin/Tcf signaling pathway.

Alternate JournalMutat. Res.
PubMed ID12351151
Grant ListR01 CA080176-03 / CA / NCI NIH HHS / United States
CA80176 / CA / NCI NIH HHS / United States
R01 CA065525-08 / CA / NCI NIH HHS / United States
R01 CA080176-02 / CA / NCI NIH HHS / United States
R01 CA065525-09 / CA / NCI NIH HHS / United States
T32 ES0707060 / ES / NIEHS NIH HHS / United States
R01 CA080176-05 / CA / NCI NIH HHS / United States
CA65525 / CA / NCI NIH HHS / United States
R01 CA065525-07 / CA / NCI NIH HHS / United States
R01 CA080176-04 / CA / NCI NIH HHS / United States
R01 CA065525-06A1 / CA / NCI NIH HHS / United States