Aloe-emodin inhibited N-acetylation and DNA adduct of 2-aminofluorene and arylamine N-acetyltransferase gene expression in mouse leukemia L 1210 cells.

Abstract

N-Acetyltransferases (NATs) plays an important role in the first step of arylamine compounds metabolism. Polymorphic NAT is coded for rapid or slow acetylatoion phenotypes, which are recognized to affect cancer risk related to environmental exposure. Aloe-emodin has been shown to exit anticancer activity. The purpose of this study is to examine whether or not aloe-emodin could affect arylamine N-acetyltransferase (NAT) activity and gene expression (NAT mRNA) and DNA-2-aminofluorene (DNA-AF) adduct formation in mouse leukemia cells (L 1210). By using high performance liquid chromatography, N-acetylation and non-N-acetylation of AF were determined and quantitated. By using reverse transcriptase-polymerase chain reaction (RT-PCR) and PCR, NAT mRNA was determined and quantitated. Aloe-emodin displayed a dose-dependent inhibition to cytosolic NAT activity and intact mice leukemia cells. Time-course experiments indicated that N-acetylation of AF measured from intact mice leukemia cells were inhibited by aloe-emodin for up to 24h. Using standard steady-state kinetic analysis, it was demonstrated that aloe-emodin was a possible uncompetitive inhibitor to NAT activity in cytosols. The DNA-AF adduct formation in mouse leukemia cells were inhibited by aloe-emodin. The NAT1 mRNA in mouse leukemia cells were also inhibited by aloe-emodin. This report is the first demonstration which showed aloe-emodin affect mice leukemia cells NAT activity, gene expression (NAT1 mRNA) and DNA-AF on adduct formation.

• Authors: Jing-Gung Chung, Yu-Ching Li, Yi-Min Lee, Jing-Pin Lin, Kwork-Chui Cheng, Weng-Cheng Chang
• Journal: Leukemia research (Leuk Res) Vol. 27 Issue 9 Pg. 831-40 (Sep 2003) ISSN: 0145-2126 [Print] England
• PMID: 12804642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• DNA Adducts
• DNA Primers
• DNA, Neoplasm
• Enzyme Inhibitors
• Fluorenes
• RNA, Messenger
• RNA, Neoplasm
• 2-aminofluorene
• 2-Acetylaminofluorene
• aloe emodin
• Arylamine N-Acetyltransferase
• Emodin

Topics

• 2-Acetylaminofluorene (metabolism)
• Acetylation (drug effects)
• Animals
• Anthraquinones
• Arylamine N-Acetyltransferase (genetics, metabolism)
• Chromatography, High Pressure Liquid
• DNA Adducts (drug effects, metabolism)
• DNA Primers (chemistry)
• DNA, Neoplasm (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Emodin (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Fluorenes (metabolism)
• Gene Expression Regulation, Enzymologic (drug effects)
• Kinetics
• Leukemia L1210 (metabolism, pathology)
• Mice
• RNA, Messenger (metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction