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J Pharmacol Exp Ther. 2014 Nov;351(2):270-7. doi: 10.1124/jpet.114.216754. Epub 2014 Aug 19.

Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole.

Author information

1
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (F.L.); Biochemistry Programme, School of Life Sciences, Faculty of Science (F.L), Food and Nutritional Sciences Programme , School of Life Sciences, Faculty of Science (T.Y.W., L.K.L.), Department of Orthopaedics and Traumatology, Faculty of Medicine (Si.C., W.C.), and School of Biomedical Sciences, Faculty of Medicine (F.L.C.), The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Food Science, National Chiayi University, Chiayi City, Taiwan, Republic of China (S.L.); and Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California (Sh.C.).
2
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (F.L.); Biochemistry Programme, School of Life Sciences, Faculty of Science (F.L), Food and Nutritional Sciences Programme , School of Life Sciences, Faculty of Science (T.Y.W., L.K.L.), Department of Orthopaedics and Traumatology, Faculty of Medicine (Si.C., W.C.), and School of Biomedical Sciences, Faculty of Medicine (F.L.C.), The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Food Science, National Chiayi University, Chiayi City, Taiwan, Republic of China (S.L.); and Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California (Sh.C.) laikleung@cuhk.edu.hk.

Abstract

Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for breast cancer. Their adverse side effect on blood lipid is well documented. Some natural compounds have been shown to be potential AIs. In the present study, we compared the efficacy of the flavonoid luteolin to the clinically approved AI letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a mouse model. In the in vitro experimental results for aromatase inhibition, the Ki values of luteolin and letrozole were estimated to be 2.44 µM and 0.41 nM, respectively. Both letrozole and luteolin appeared to be competitive inhibitors. Subsequently, an animal model was used for the comparison. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by intravenous injection. Similar to letrozole, luteolin administration reduced plasma estrogen concentrations and suppressed the xenograft proliferation. The regulation of cell cycle and apoptotic proteins-such as a decrease in the expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was about the same in both treatments. The most significant disparity was on blood lipids. In contrast to letrozole, luteolin increased fasting plasma high-density lipoprotein concentrations and produced a desirable blood lipid profile. These results suggested that the flavonoid could be a coadjuvant therapeutic agent without impairing the action of AIs.

PMID:
25138022
DOI:
10.1124/jpet.114.216754
[Indexed for MEDLINE]
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