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  • Title: DNA topoisomerase II as the primary cellular target for salvicine in Saccharomyces cerevisiae.
    Author: Meng LH, He XX, Zhang JS, Ding J.
    Journal: Acta Pharmacol Sin; 2001 Aug; 22(8):741-6. PubMed ID: 11749849.
    Abstract:
    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.
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