Chemopreventive Effects of Orange Peel Extract (OPE) II. OPE Inhibits Atypical Hyperplastic Lesions in Rodent Mammary Gland

Abstract

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; (3) 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.