Amsacrine and etoposide hypersensitivity of yeast cells overexpressing DNA topoisomerase II.

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Nitiss JL, Liu YX, Harbury P, Jannatipour M, Wasserman R, Wang JC

Amsacrine and etoposide hypersensitivity of yeast cells overexpressing DNA topoisomerase II.

Cancer Res. 1992 Aug 15;52(16):4467-72.

PubMed ID

1322791 [ View in PubMed

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Abstract

Increasing the cellular concentration of DNA topoisomerase II in yeast by expressing constitutively a plasmid-borne TOP2 gene encoding the enzyme greatly increases the sensitivity of the cells to amsacrine and etoposide (VP-16). This increased drug sensitivity at a higher intracellular DNA topoisomerase II level is observed in both RAD52+ repair-proficient strains and rad52 mutants that are defective in the repair of double-stranded breaks. These results provide strong support of the hypothesis that the cellular target of these drugs is DNA topoisomerase II, and that these drugs kill cells by converting DNA topoisomerase II into a DNA damaging agent.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amsacrine	DNA topoisomerase 2-alpha	Protein	Humans	Yes	Inhibitor	Details