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

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

Kyungpook National University
Seoul National University

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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 K_i 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.

Original language	English
Pages (from-to)	94-99
Number of pages	6
Journal	Food and Chemical Toxicology
Volume	70
DOIs	https://doi.org/10.1016/j.fct.2014.04.020
State	Published - Aug 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CYP2J2
Cytotoxicity
Decursin
Drug interactions
Human liver microsomes

Access to Document

10.1016/j.fct.2014.04.020

Cite this

@article{4d0b5c04991844cdb2c35f1c53bedfa9,

title = "Potential of decursin to inhibit the human cytochrome P450 2J2 isoform",

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",

author = "Boram Lee and Zhexue Wu and Sung, \{Sang Hyun\} and Taeho Lee and Song, \{Kyung Sik\} and Lee, \{Min Young\} and Liu, \{Kwang Hyeon\}",

year = "2014",

month = aug,

doi = "10.1016/j.fct.2014.04.020",

language = "English",

volume = "70",

pages = "94--99",

journal = "Food and Chemical Toxicology",

issn = "0278-6915",

publisher = "Elsevier Ltd.",

}

TY - JOUR

T1 - Potential of decursin to inhibit the human cytochrome P450 2J2 isoform

AU - Lee, Boram

AU - Wu, Zhexue

AU - Sung, Sang Hyun

AU - Lee, Taeho

AU - Song, Kyung Sik

AU - Lee, Min Young

AU - Liu, Kwang Hyeon

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - CYP2J2

KW - Cytotoxicity

KW - Decursin

KW - Drug interactions

KW - Human liver microsomes

UR - https://www.scopus.com/pages/publications/84901674295

U2 - 10.1016/j.fct.2014.04.020

DO - 10.1016/j.fct.2014.04.020

M3 - Article

C2 - 24788058

AN - SCOPUS:84901674295

SN - 0278-6915

VL - 70

SP - 94

EP - 99

JO - Food and Chemical Toxicology

JF - Food and Chemical Toxicology

ER -

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

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this