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KMID : 0857020060210010344
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Kosin Medical Journal
2006 Volume.21 No. 1 p.344 ~ p.348
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Effects of irinotecan on the activity and expression of topoisomerase Ⅰand Ⅲ in HL-60 human leukemia cells
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Jeong In-Cheol
Cho Moo-Youn
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Abstract
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Background DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA. DNA topoisomerases have been shown to be the molecular targets of many antimicrobial and anticancer agents. Among topoisomerase- targeting drugs in clinical use at present, most act by trapping the covalent DNA-enzyme intermediates to convert a normal cellular enzyme to a DNA damaging agent.
This studies were designed to elucidate whether pretreatment of HL-60 human leukemia cells with the topoisomerase Ⅰ - directed drug irinotecan would increase the expression of topoisomerases and to investigate the activity of topoisomerase mediated by irinotecan in nuclear extract from HL-60 human leukemia cells. Methods We have conducted experiments on cell cytotoxicity in drug-treated HL-60 cells, topoisomerase purification, topoisomerase assay using gel electrophores and oligo chip microarray analysis, respectively. Results Irinotecan inhibited the relaxation activity of topoisomerase in pUC19 DNA at various concentrations (range 0.4-50 μM). Irinotecan IC(50) values was 1 uM for HL-60 cells. The levels of the topoisomerase Ⅰ(type IB) Ⅲ(type IA) mRNA remained no significant change from oligo chip microarray analysis. Conclusion Our results suggest that topoisomerase I protein is one of the cellular targets of irinotecan but this drug does not coordinate regulation with type Ⅰ topoisomerase mRNA levels.
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KEYWORD
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Irinotecan, Topoisomerase activity, Expression, HL-60 cells
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