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The citrus flavonone hesperetin inhibits growth of aromatase‐expressing MCF‐7 tumor and reduces the effective dose in letrozole‐treated mice
Author(s) -
LI Fengjuan,
Ye Lan,
Chan Franky L.,
Chen Shiuan,
Leung Lai K.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1023.16
Subject(s) - hesperetin , letrozole , aromatase , aromatase inhibitor , mcf 7 , pharmacology , breast cancer , estrogen , chemistry , cancer research , medicine , endocrinology , adjuvant , cancer , biochemistry , human breast , flavonoid , antioxidant
Breast cancer is one of the most prevalent cancers affecting women. Aromatase is a key enzyme in estrogen synthesis, and aromatase inhibition is a contemporary adjuvant therapy for treating estrogen‐responsive breast cancer. In the present study, we examined the aromatase inhibitory effect of hesperetin and the combined effect of hesperetin and letrozole on an established postmenopausal breast cancer model. Athymic mice were ovariectomized and transplanted with aromatase‐overexpressing MCF‐7 cells. Our first experiment has shown that dietary administration of hesperetin at 1000 ppm and 5000ppm significantly deterred the xenograft growth. The combined treatment effect of hesperetin and letrozole was examined in a follow up experiment. Our result indicated that hesperetin could improve the potency of letrozole by about 10‐folds. Messenger RNA expression of the estrogen‐responsive gene pS2 was also decreased in the tumors of mice treated with hesperetin. Western analysis indicated that cyclin D1, CDK4 and Bcl‐x(L) were reduced in the tumors. This study suggested that hesperetin could be a potential co‐therapeutic agent to aromatase inhibitor.