Bioactivation of the phytoestrogen diosmetin by CYP1 cytochromes P450

被引：76

作者：

Androutsopoulos, Vasilis ^{[1
]}

Wilsher, Nicola ^{[1
]}

Arroo, Randolph R. J. ^{[1
]}

Potter, Gerry A. ^{[1
]}

机构：

[1] De Montfort Univ, Leicester Sch Pharm, Leicester LE1 9BH, Leics, England

来源：

CANCER LETTERS | 2009年 / 274卷 / 01期

关键词：

CYP1A1; CYP1B1; MCF-7; cells; Natural products; Flavone; ARYL-HYDROCARBON RECEPTOR; HUMAN LIVER-MICROSOMES; BREAST-CANCER CELLS; INHIBITION; FLAVONOIDS; LUTEOLIN; METABOLISM; ENZYMES; BINDING; 1A1;

D O I：

10.1016/j.canlet.2008.08.032

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Breast cancer is a major Cause of death worldwide. Amongst the various forms of treatment chemoprevention is favoured and natural products such as the dietary flavonoids have been examined for their cancer preventative activity. In this study we investigated the anticancer activity of the flavonoid diosmetin, as a result of cytochrome P450 CYP1 metabolism. Diosmetin was metabolized to luteolin via an aromatic demethylation reaction on the B-ring from CYP1A1, CYP1B1 and the hepatic isozyme CYP1A2. CYP1A1 and CYP1A2 also produced additional unidentified metabolites. CYP1B1 showed the lowest apparent KM and CYP1A1 the highest apparent Kcat. Diosmetin was also metabolized to luteolin in estrogen receptor positive breast cell-line (MCF-7 cells) preinduced for 24 11 with the potent CYP1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment of MCF-7 cells with TCDD caused bioactivation of diosmetin enhancing its cytotoxicity. Taken together these data suggest that the flavonoid diosmetin is metabolised to the more active molecule luteolin by CYP1 family enzymes. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：54 / 60

页数：7

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