KMID : 0613820000100060621
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Journal of Life Science 2000 Volume.10 No. 6 p.621 ~ p.629
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Effects of camptothecin on the expression of DNA topoisomerase I and c-myc in HL-60 human leukemia cells
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Abstract
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Camptothecin (CPT) is an antitumor alkaloid that has been isolated from the Chinese tree, Camptotheca acuminata. The cytotoxicity of CPT has been correlated to its inhibition of DNA topoisomerase (Topo) I by stabilizing drug-enzyme-DNA ¡°cleavable complex" resulting in DNA single-strand breaks and DNA-protein crosslinks. This studies were designed to elucidate whether CPT regulates Topo I mediated by CPT in DNAs containing c-myc protooncogene. We have conducted experiments on Topo I purification, pUC-MYC I cloning and Topo I assay using electrophoresis, quantitative RT-PCR and Northern blotting techniques. CPT ingibited the relaxation activity of Topo I in pUC19 DNA at various concentrations (1-1000 ¥ìM), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 ¥ìM). In HL-60 cells treated with CPT, the expression of c-myc gene was decreased over that in the control group with no changes in the expression of Topo I mRNA. Our results suggest that Topo I is the target of CPT cytotoxicity but it does not affect Topo I extression, and the suppression of c-myc mRNA expression by CPT is due to c-myc damage resulted from formation of a cleavable complex with CPT.
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KEYWORD
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