title: The citrus flavonone hesperetin prevents letrozole-induced bone loss in a mouse model of breast cancer.
abstract: Aromatase is a key enzyme in estrogen synthesis, and aromatase inhibitors (AIs) have been developed for treating estrogen-responsive breast cancer. Because of its nondiscriminatory inhibition of estrogen synthesis, patients treated with AIs also contract diseases typically associated with estrogen deficiency, such as bone deterioration. Our laboratory found that the citrus flavonone hesperetin could inhibit aromatase, and the selective estrogen receptor modulator nature of flavonoid might counteract the undesirable effect of AIs. In the present study, we employed an established postmenopausal model for breast carcinogenesis to examine the drug interaction between hesperetin and letrozole, one of the AIs. Athymic mice were ovariectomized and transplanted with aromatase-overexpressing MCF-7 cells (MCF-7aro). Hesperetin was administered in the diet at 5000 ppm, and letrozole was injected sc at different doses. Results showed that either hesperetin or letrozole could reduce plasma estrogen level and inhibit tumor growth. Most importantly, the letrozole-induced bone loss measured as bone volume fraction was reversed by hesperetin without compromising on the deterrence of MCF-7aro tumor growth. Taken together, the present study suggested that hesperetin could be a potential cotherapeutic agent to AI.
authors.affiliation: Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Li
authors.forename: Simon
authors.initials: S
authors.lastname: Chow
authors.forename: Wing-hoi
authors.initials: WH
authors.lastname: Cheung
authors.forename: Franky L
authors.initials: FL
authors.lastname: Chan
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002957:Citrus / Q000737:chemistry*; D004958:Estradiol / Q000097:blood; D005260:Female; D006569:Hesperidin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000077289:Letrozole; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009570:Nitriles / Q000009:adverse effects*; D010024:Osteoporosis / Q000139:chemically induced / Q000517:prevention & control*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014230:Triazoles / Q000009:adverse effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D020845:Selective Estrogen Receptor Modulators; D014230:Triazoles; D004958:Estradiol; D000077289:Letrozole; D006569:Hesperidin; C013015:hesperetin