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

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

31 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

Keywords

CYP2J2
Cytotoxicity
Decursin
Drug interactions
Human liver microsomes

UN SDGs

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

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10.1016/j.fct.2014.04.020

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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",

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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

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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

Keywords

UN SDGs

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