Potential of decursin to inhibit the human cytochrome P450 2J2 isoform.
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.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Boram
B
Lee
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Zhexue
Z
Wu
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Republic of Korea.
Sang Hyun
SH
Sung
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Taeho
T
Lee
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Kyung-Sik
KS
Song
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: vetmedic@knu.ac.kr.
Min Young
MY
Lee
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: dstlkh@knu.ac.kr.
Kwang-Hyeon
KH
Liu
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D000090762:Cytochrome P-450 CYP2J2; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D053719:Tandem Mass Spectrometry
D001578:Benzopyrans; D001688:Biological Products; D002087:Butyrates; C000717350:CYP2J2 protein, human; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; C101278:decursin; D000090762:Cytochrome P-450 CYP2J2
CYP2J2; Cytotoxicity; Decursin; Drug interactions; Human liver microsomes