DNA topoisomerase II as the primary cellular target for salvicine in Saccharomyces cerevisiae

Acta Pharmacol Sin. 2001 Aug;22(8):741-6.


Aim: To identify whether DNA topoisomerase II (Topo II) is the primary cellular target of salvicine in Saccharomyces cerevisiae (S cerevisiae) and the action mode of salvicine.

Methods: The catalytic activity of Topo II was determined by Topo II mediated supercoiled pBR322 relaxation. The effects of salvicine on the growth of four strains of S cerevisiae were assessed by clone forming assay.

Results: Salvicine inhibited Topo II mediated supercoiled pBR322 relaxation in cell-free system. Cytotoxicities of salvicine to parent (JN394) and TOP1 deleted (JN394top1-) yeast cells were at the same level, suggesting Topo I might not be the cellular target of salvicine. Salvicine displayed high activity against JN394t2-1 cells at 25 degrees C, while no growth inhibition was observed at 30 degrees C in the concentration range of interest. Furthermore, JN394t2-5 cells which expressed top2-5 mutant allele were highly resistant to salvicine and etoposide (VP16).

Conclusion: Topo II was the primary cellular target of salvicine in vivo and salvicine killed yeast cells mainly by trapping the DNA-Topo II cleavage complex. Salvicine and VP16 might share some similar action locus on Topo II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytotoxicity, Immunologic / drug effects
  • DNA Topoisomerases, Type II / drug effects
  • DNA Topoisomerases, Type II / metabolism*
  • Etoposide / pharmacology
  • Naphthoquinones / pharmacology*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / growth & development*


  • Naphthoquinones
  • salvicine
  • Etoposide
  • DNA Topoisomerases, Type II