Tumor cell death induced by topoisomerase-targeting drugs

T. K. Li, Leroy-Fong Liu

Research output: Contribution to journalArticle

442 Citations (Scopus)

Abstract

DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However, they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topoisomerase poisons, acidic pH, and oxidative stresses) can convert DNA topoisomerases into DNA-breaking nucleases, resulting in cell death and/or genomic instability. The importance of topoisomerase-mediated DNA cleavage in tumor cell death and carcinogenesis has been recognized. This review focuses on recent findings concerning the molecular mechanisms of the stress responses to topoisomerase-mediated DNA damage. The involvement of ubiquitin/26S proteasome and SUMO/UBC9 in these processes, as well as the role of topoisomerase cleavable complexes in apoptotic cell death are discussed.

Original languageEnglish
Pages (from-to)53-77
Number of pages25
JournalAnnual Review of Pharmacology and Toxicology
Volume41
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Apoptosis
  • Camptothecin
  • SUMO
  • Topoisomerase
  • Ubiquitin

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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