Abstract |
CYP2J2 enzyme is highly expressed in human tumors and carcinoma cell lines, and epoxyeicosatrienoic acids, CYP2J2-mediated metabolites, have been implicated in the pathologic development of human cancers. To identify a CYP2J2 inhibitor, 50 natural products obtained from plants were screened using astemizole as a CYP2J2 probe substrate in human liver microsomes. Of these, decursin noncompetitively inhibited CYP2J2-mediated astemizole O-demethylation and terfenadine hydroxylation activities with Ki values of 8.34 and 15.8μM, respectively. It also showed cytotoxic effects against human hepatoma HepG2 cells in a dose-dependent manner while it did not show cytotoxicity against mouse hepatocytes. The present data suggest that decursin is a potential candidate for further evaluation for its CYP2J2 targeting anti- cancer activities. Studies are currently underway to test decursin as a potential therapeutic agent for cancer.
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Authors | Boram Lee, Zhexue Wu, Sang Hyun Sung, Taeho Lee, Kyung-Sik Song, Min Young Lee, Kwang-Hyeon Liu |
Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
(Food Chem Toxicol)
Vol. 70
Pg. 94-9
(Aug 2014)
ISSN: 1873-6351 [Electronic] England |
PMID | 24788058
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Benzopyrans
- Biological Products
- Butyrates
- CYP2J2 protein, human
- Cytochrome P-450 Enzyme Inhibitors
- Isoenzymes
- Cytochrome P-450 Enzyme System
- decursin
- Cytochrome P-450 CYP2J2
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Topics |
- Animals
- Benzopyrans
(pharmacology)
- Biological Products
(pharmacology)
- Butyrates
(pharmacology)
- Cell Survival
(drug effects)
- Chromatography, Liquid
- Cytochrome P-450 CYP2J2
- Cytochrome P-450 Enzyme Inhibitors
(pharmacology)
- Cytochrome P-450 Enzyme System
(metabolism)
- Hep G2 Cells
- Hepatocytes
(drug effects, metabolism)
- Humans
- Hydroxylation
- Isoenzymes
(metabolism)
- Male
- Mice
- Mice, Inbred ICR
- Microsomes, Liver
(drug effects, enzymology)
- Tandem Mass Spectrometry
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