RT Journal Article
SR Electronic
T1 Induction of Cytochromes P450 1A1 and 1B1 by Emodin in Human Lung Adenocarcinoma Cell Line CL5
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1229
OP 1235
VO 29
IS 9
A1 Hui-Wu Wang
A1 Ta-Liang Chen
A1 Pan-Chyr Yang
A1 Tzuu-Huei Ueng
YR 2001
UL http://dmd.aspetjournals.org/content/29/9/1229.abstract
AB Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is an active compound of many laxative herbal drugs. The present study aimed to determine the effects of emodin on cytochrome P450 (P450)-dependent monooxygenases of human lung adenocarcinoma CL5 cells. Treatment of CL5 cells with 100 μM emodin for 24 h induced benzo[a]pyrene hydroxylation, 7-ethoxyresorufinO-deethylation, and 7-ethoxycoumarinO-deethylation activities of S9 fractions. Immunoblot analysis of CL5 S9 proteins revealed that emodin induced proteins immunorelated to P450s 1A1 and 1B1. Northern blot analysis of total cellular RNA showed that emodin induced P450s 1A1 and 1B1 mRNA levels in CL5 cells. These inductive effects on P450 monooxygenase activity, protein, and mRNA were concentration- and time-dependent. Addition of emodin to CL5 cell S9 inhibited its 7-ethoxycoumarinO-deethylation activity. Treatment of CL5 cells with 10 μM 3-methylcholanthrene for 24 h induced monooxygenase activity and P450s 1A1 and 1B1 proteins and mRNA levels. Treatment of the lung cells with 100 μM emodin or purpurin (1,2,4-trihydroxyanthraquinone) for 24 h produced greater induction of P450s 1A1 and 1B1 mRNA than did anthraflavic acid (2,6-dihydroxyanthraquinone) or anthraquinone. The emodin treatment induced P450s 1A1 and 1B1 mRNA in human lung carcinoma NCI-H322 and breast cancer MCF-7 cells. Emodin induced P450 1A1, but not 1B1, mRNA in human hepatoma HepG2 cells. The present study demonstrates that emodin is an inducer of P450s 1A1 and 1B1 protein and mRNA in human lung adenocarcinoma CL5 cells. Modulation of P450 by emodin may be an important factor affecting metabolism and toxicity of the hydroxyanthraquinone in humans. The American Society for Pharmacology and Experimental Therapeutics