Potential of decursin to inhibit the human cytochrome P450 2J2 isoform

Boram Lee; Zhexue Wu; Sang Hyun Sung; Taeho Lee; Kyung-Sik Song; Min Young Lee; Kwang-Hyeon Liu

doi:10.1016/j.fct.2014.04.020

Potential of decursin to inhibit the human cytochrome P450 2J2 isoform

Food Chem Toxicol. 2014 Aug:70:94-9. doi: 10.1016/j.fct.2014.04.020. Epub 2014 Apr 29.

Authors

Boram Lee¹, Zhexue Wu¹, Sang Hyun Sung², Taeho Lee¹, Kyung-Sik Song¹, Min Young Lee³, Kwang-Hyeon Liu⁴

Affiliations

¹ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
² College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Republic of Korea.
³ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: vetmedic@knu.ac.kr.
⁴ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: dstlkh@knu.ac.kr.

PMID: 24788058
DOI: 10.1016/j.fct.2014.04.020

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.

Keywords: CYP2J2; Cytotoxicity; Decursin; Drug interactions; Human liver microsomes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Hepatocytes / metabolism
Humans
Hydroxylation
Isoenzymes / metabolism
Male
Mice
Mice, Inbred ICR
Microsomes, Liver / drug effects
Microsomes, Liver / enzymology
Tandem Mass Spectrometry

Substances

Benzopyrans
Biological Products
Butyrates
CYP2J2 protein, human
Cytochrome P-450 Enzyme Inhibitors
Isoenzymes
Cytochrome P-450 Enzyme System
decursin
Cytochrome P-450 CYP2J2