Suppression of tumorigenesis in the Apc(min) mouse: down-regulation of beta-catenin signaling by a combination of tea plus sulindac.
Epidemiological and animal studies suggest that tea may be protective towards cancers of the GI tract. White tea, the least processed form of tea, contains high levels of polyphenols and, like green tea, is chemopreventive towards heterocyclic amine-initiated colonic aberrant crypt formation in male F344 rats. We examined for the first time the relative effectiveness of white and green tea in suppressing intestinal tumorigenesis in C57BL/6J-Apc(Min/+) (Apc(min)) mice. Each tea was also compared with sulindac, a non-steroidal anti-inflammatory drug known to be highly effective in Apc(min) mice. Male C57BL/6J (+/+) (wild-type) and Apc(min) mice were treated in the drinking water with white tea or green tea (1.5% w/v, 2 min brew-time), 80 p.p.m. sulindac, a combination of 80 p.p.m. sulindac in 1.5% white tea, or pH buffered water. After 12 weeks of treatment, Apc(min) mice given white tea, green tea, or sulindac had significantly fewer tumors than controls (P < 0.05). The protection provided by 1.5% green or white tea was comparable to that provided by 80 p.p.m. sulindac. Mice treated with a combination of white tea plus sulindac had significantly fewer tumors than either treatment alone (P < 0.05). beta-catenin and beta-catenin/Tcf-4 regulated proteins Cyclin D(1) and c-Jun were readily detected in polyps, but markedly reduced in normal-looking intestines of mice treated with both tea and sulindac. This research provides evidence that teas, particularly when administered in combination with sulindac, are highly effective at inhibiting intestinal neoplasia in male Apc(min) mice via direct or indirect effects on the beta-catenin/APC pathway.
Orner
Gayle A
GA
Linus Pauling Institute and Environmental and Molecular Toxicology Department, Oregon State University, Corvallis, OR 97331, USA. gayle.orner@orst.edu
Dashwood
W-Mohaiza
WM
Blum
Carmen A
CA
Díaz
G Darío
GD
Li
Qingjie
Q
Dashwood
Roderick H
RH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D017491:Genes, APC; D007417:Intestinal Polyps / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000187:drug effects*; D013467:Sulindac / Q000494:pharmacology*; D013662:Tea; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
D000894:Anti-Inflammatory Agents, Non-Steroidal; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D013662:Tea; D015534:Trans-Activators; D051176:beta Catenin; D013467:Sulindac