Cell death induced by topoisomerase-targeted drugs: More questions than answers

Research output: Contribution to journalArticle

283 Citations (Scopus)

Abstract

Chemotherapeutic agents that target topoisomerase I and II set into motion a series of biochemical changes that culminate in cell death, but only under some conditions. The realization that stabilization of covalent topoisomerase-DNA complexes is not sufficient to insure cell death has prompted investigators to examine various aspects of the drug-induced death process itself. Several discrete steps along this pathway have been identified, including (a) the processing of stabilized cleavage complexes into frank DNA strand breaks; (b) sensing of the DNA damage, leading to activation of stress-associated signaling pathways and cell cycle arrest; and (c) activation of a preexisting group of enzymes and enzyme precursors, typified by the cysteine-dependent aspartate-directed proteases (caspases), that catalyze the relatively orderly biochemical cascade of terminal events known as apoptosis. The present review discusses the evidence that these steps occur after treatment with etoposide or camptothecin, the two prototypic topoisomerase poisons that are commonly studied. As in any emerging area, a large number of questions remain to be answered about the process of cell death induced by topoisomerase-directed drugs.

Original languageEnglish (US)
Pages (from-to)195-211
Number of pages17
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1400
Issue number1-3
DOIs
StatePublished - Oct 1 1998

Fingerprint

Cell death
Type I DNA Topoisomerase
Cell Death
Chemical activation
Pharmaceutical Preparations
Camptothecin
Type II DNA Topoisomerase
Enzyme Precursors
DNA Breaks
Poisons
DNA
Etoposide
Cell Cycle Checkpoints
Aspartic Acid
DNA Damage
Cysteine
Peptide Hydrolases
Stabilization
Cells
Research Personnel

Keywords

  • Apoptosis
  • Camptothecin
  • Caspase
  • DNA repair
  • DNA topoisomerase
  • Etoposide
  • Mutation
  • Phosphatase
  • Topoisomerase

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology
  • Biophysics

Cite this

Cell death induced by topoisomerase-targeted drugs : More questions than answers. / Kaufmann, Scott H.

In: Biochimica et Biophysica Acta - Gene Structure and Expression, Vol. 1400, No. 1-3, 01.10.1998, p. 195-211.

Research output: Contribution to journalArticle

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