Suppression of tumorigenesis in the Apc^min mouse: Down-regulation of β-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 nonsteroidal 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). β-catenin and β-catenin/Tcf-4 regulated proteins Cyclin D₁ 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 β-catenin/APC pathway.