Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Effects of camptothecin on the expression of DNA topoisomerase I and c-myc in HL-60 human leukemia cells

HL-60 사람 백혈병 세포에서 camptothecin이 DNA topoisomerase l과 c-myc의 발현에 미치는 영향

  • 정인철 (고신대학교 의학부 생화학교실) ;
  • 정대성 (고신대학교 의학부 생화학교실) ;
  • 류경자 (부산대학교 자연과학대학 화학과) ;
  • 박장수 (부산대학교 자연과학대학 화학과) ;
  • 조무연 (고신대학교 의학부 생화학교실)
  • Published : 2000.12.01
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Abstract

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 $\mu$M), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 $\mu$M). 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. CPT.

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