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Orange peel is a rich source of flavonoids with polymethoxyflavones as major constituents, compounds asso-ciated with potential antioxidant, anti-inflammatory, and antitumor activities. We studied the effect of an orange peel extract(OPE) on intestinal tumor growth in ApcMin/. mice, a mouse model for human familial adenomatous polyposis (FAP). TheOPE contained 30% polymethoxyflavones, a mixture that included tangeretin (19.0%), heptamethoxyflavone (15.24%), tetram-ethoxyflavone (13.6%), nobiletin (12.49%), hexamethoxyflavone (11.06%), and sinensitin (9.16%). ApcMin/. mice were fedi.e., AIN-76A diet modified with decreasedcalcium, vitamin D, and methyl-donor nutrients and increased lipid content); (3) NWD with 0.25% OPE; and (4) NWD with0.5% OPE, with all additives premixed in the diet. After 9 weeks of feeding NWD to the ApcMin/. mice, tumors increasedmainly in the colon, with tumor multiplicity increasing 5.3-fold and tumor volume increasing 6.7-fold. After feeding 0.5%OPE in NWD, the development of tumors markedly decreased, with multiplicity decreasing 49% in the small intestine and38% in the colon. NWD also led to increased apoptosis in intestinal tumors, and 0.5% OPE in NWD further increased apop-model of FAP, and increased apoptosis may have contributed to this effect.