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KMID : 0613820110210111558
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Journal of Life Science
2011 Volume.21 No. 11 p.1558 ~ p.1564
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Screening of Potential Anticancer Compounds from Marketed Drugs: Aripiprazole, Haloperidol, Miconazole, and Terfenadine Inhibit Cytochrome P450 2J2
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Liu Kwang-Hyeon
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Abstract
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Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation (IC_{50}=11.2 μM) and terfenadine hydroxylation (IC_{50}=2.2 μM), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation (IC_{50}=13.6 μM) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.
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KEYWORD
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Anti-cancer activity, CYP2J2, drug-interaction, miconazole, screening
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