생명과학회지 (Journal of Life Science)

  • 제10권6호
  • /
  • Pages.621-629
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  • 2000
  • /
  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지

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

Effects of camptothecin on the expression of DNA topoisomerase I and c-myc in HL-60 human leukemia cells

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

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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