Identification of mammalian dna topoisomerase i as an intracellular target of the anticancer drug camptothecin

Yaw Huei Hsiang, Leroy F. Liu

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909 引文 斯高帕斯(Scopus)

摘要

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 campto-thedn-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 camptotheScin-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.

原文英語
頁(從 - 到)1722-1726
頁數5
期刊Cancer Research
48
發行號7
出版狀態已發佈 - 1988
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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