Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis.

Epidemiological studies consistently indicate that consump- enzymes and reduce the expression of ornithine decarboxylase tion of fruits and vegetables lowers cancer risk in humans (8–10). Finally, plant phenolics both inhibit cell proliferation and suggest that certain dietary constituents may be effect- and induce cell death or differentiation in tumor cells, sugive in preventing colon cancer. Plant-derived phenolic gesting that they may antagonize all phases of carcinogenesis compounds manifest many beneficial effects and can poten- (7,11–13). tially inhibit several stages of carcinogenesis in vivo. In this Caffeic acid phenethyl ester (CAPE) and curcumin (Figure study, we investigated the efficacy of several plant-derived 1) characterize plant phenolics that are structurally related to phenolics, including caffeic acid phenethyl ester (CAPE), 3,4-dihydroxycinnamic acid (6). CAPE may be obtained from curcumin, quercetin and rutin, for the prevention of tumors propolis, a substance produced by the bark of conifer trees in C57BL/6J-Min/ (Min/) mice. These animals bear a and carried by honeybees to their hives (14). Curcumin is the germline mutation in the Apc gene and spontaneously yellow pigment of tumeric and mustard that is widely used develop numerous intestinal adenomas by 15 weeks of age. for flavoring and coloring in foods. Both CAPE and curcumin At a dietary level of 0.15%, CAPE decreased tumor are effective in vitro inhibitors of the growth of transformed formation in Min/ mice by 63%. Curcumin induced a cells (15–20) and in vivo inhibitors of tumor initiation and similar tumor inhibition. Quercetin and rutin, however, promotion in different carcinogen-induced rodent models both failed to alter tumor formation at dietary levels of (14,21–26). 2%. Examination of intestinal tissue from the treated Flavonoids constitute another promising class of dietary animals showed that tumor prevention by CAPE and antioxidants that are ubiquitously found in fruits, vegetables curcumin was associated with increased enterocyte and tea. Like the cinnamates, these phytochemicals exhibit apoptosis and proliferation. CAPE and curcumin also anti-inflammatory activity and inhibit tumor cell growth in decreased expression of the oncoprotein β-catenin in the culture and animal bioassays. Quercetin is the most common enterocytes of the Min/ mouse, an observation previously biologically active flavonoid. The glycosidic derivatives of the associated with an antitumor effect. These data place the flavonoids are preferentially absorbed in humans (6). Rutin is plant phenolics CAPE and curcumin among a growing list the glycoside form of quercetin and is hydrolyzed to quercetin of anti-inflammatory agents that suppress Apc-associated by colonic microflora, possibly enhancing its bioavailability intestinal carcinogenesis. in the colon (27). Quercetin and rutin inhibit neoplasia in carcinogen-induced skin and colon cancer models (25,26,28– 30).