Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin

Y. H. Hsiang, Leroy-Fong Liu

Research output: Contribution to journalArticle

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Abstract

Camptothecin, a plant alkaloid with antitumor activity, has been shown to be a potent inhibitor of nucleic acid synthesis and a strong inducer of DNA strand breaks in mammalian cells. Previous studies have shown that camptothecin inhibits purified mammalian DNA topoisomerase I by trapping a reversible enzyme-DNA 'cleavable complex' (Hsiang et al., J. Biol. Chem., 260: 14873-14878, 1985). Our present studies, using L1210 cells and SV40-infected monkey cells, have shown that camptothecin-induced strand breaks are protein linked. The linked protein is most likely DNA topoisomerase I as revealed by immunoblot analysis, using antibodies against purified mammalian DNA topoisomerase I. Brief heating of camptothecin-treated cells to 65°C resulted in a rapid reduction of the number of protein-linked DNA breaks. Reversal of the camptothecin-induced topoisomerase I-DNA complex by heat was also observed in an in vitro system by using purified mammalian DNA topoisomerase I. Our results suggest that camptothecin interferes with DNA topoisomerase I both in cultured mammalian cells and in the purified system by trapping a reversible enzyme-DNA cleavable complex.

Original languageEnglish
Pages (from-to)1722-1726
Number of pages5
JournalCancer Research
Volume48
Issue number7
Publication statusPublished - 1988
Externally publishedYes

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Camptothecin
Type I DNA Topoisomerase
Pharmaceutical Preparations
DNA Breaks
Nucleic Acid Synthesis Inhibitors
Proteins
DNA
Enzymes
Alkaloids
Heating
Haplorhini
Cultured Cells
Hot Temperature
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. / Hsiang, Y. H.; Liu, Leroy-Fong.

In: Cancer Research, Vol. 48, No. 7, 1988, p. 1722-1726.

Research output: Contribution to journalArticle

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