Chemopreventive effects of orange peel extract (OPE). I: OPE inhibits intestinal tumor growth in ApcMin/+ mice.

Orange peel is a rich source of flavonoids with polymethoxyflavones as major constituents, compounds associated with potential antioxidant, anti-inflammatory, and antitumor activities. We studied the effect of an orange peel extract (OPE) on intestinal tumor growth in Apc(Min/+) mice, a mouse model for human familial adenomatous polyposis (FAP). The OPE contained 30% polymethoxyflavones, a mixture that included tangeretin (19.0%), heptamethoxyflavone (15.24%), tetramethoxyflavone (13.6%), nobiletin (12.49%), hexamethoxyflavone (11.06%), and sinensitin (9.16%). Apc(Min/+) mice were fed one of four diets: (1) AIN-76A control diet; (2) a new Western-style diet (NWD), i.e., AIN-76A diet modified with decreased calcium, vitamin D, and methyl-donor nutrients and increased lipid content); (3) NWD with 0.25% OPE; and (4) NWD with 0.5% OPE, with all additives premixed in the diet. After 9 weeks of feeding NWD to the Apc(Min/+) mice, tumors increased mainly 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 and 38% in the colon. NWD also led to increased apoptosis in intestinal tumors, and 0.5% OPE in NWD further increased apoptosis in tumors of the small and large intestine. Findings indicated that OPE inhibited tumorigenesis in this preclinical mouse model of FAP, and increased apoptosis may have contributed to this effect.

Chemopreventive effects of orange peel extract (OPE). II: OPE inhibits atypical hyperplastic lesions in rodent mammary gland.

Cancer chemoprevention via the ingestion of natural substances is a current topic of considerable interest. Flavonoids are a family of biologically active phytochemicals having a variety of biological effects. Orange peel extract (OPE) is an abundant source of polymethoxyflavones (PMFs) with potential chemopreventive properties. The OPE used here was a mixture containing tangeretin (19.0%), heptamethoxyflavone (15.24%), tetramethoxyflavone (13.6%), nobiletin (12.49%), hexamethoxyflavone (11.06%), and sinensitin (9.16%). C57Bl/6 mice were fed a new "Western-style" diet (NWD), which had previously induced atypical hyperplasias in mammary gland, and NWD supplemented with a standardized OPE containing 30% PMFs. Mice were fed one of four diets: (1) AIN-76A diet (control); (2) NWD; 0.25% OPE in NWD; or (4) 0.5% OPE in NWD. After 3 months of feeding, atypical hyperplasias developed in mammary glands of mice fed NWD, but not in controls. After feeding OPE in NWD, atypical hyperplasias per mouse decreased in frequency compared to feeding NWD alone (P < .05 in mice fed 0.25% OPE). Apoptosis increased in OPE-treated groups (P < .01) with no inhibition of mitosis. Thus, a standardized preparation of OPE with 30% PMFs decreased development of an atypical hyperplastic lesion and increased apoptosis in ductal epithelial cells of mouse mammary gland.