Transport and cytotoxicity of the anticancer drug 3-bromopyruvate in the yeast Saccharomyces cerevisiae

Paweł Lis, Marek Zarzycki, Young H. Ko, Margarida Casal, Peter L. Pedersen, Andre Goffeau, Stanisław Ułaszewski

Research output: Contribution to journalArticlepeer-review

Abstract

We have investigated the cytotoxicity in Saccharomyces cerevisiae of the novel antitumor agent 3-bromopyruvate (3-BP). 3-BP enters the yeast cells through the lactate/pyruvate H + symporter Jen1p and inhibits cell growth at minimal inhibitory concentration of 1.8 mM when grown on non-glucose conditions. It is not submitted to the efflux pumps conferring Pleiotropic Drug Resistance in yeast. Yeast growth is more sensitive to 3-BP than Gleevec (Imatinib methanesulfonate) which in contrast to 3-BP is submitted to the PDR network of efflux pumps. The sensitivity of yeast to 3-BP is increased considerably by mutations or chemical treatment by buthionine sulfoximine that decrease the intracellular concentration of glutathione.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalJournal of Bioenergetics and Biomembranes
Volume44
Issue number1
DOIs
StatePublished - Feb 2012

Keywords

  • 3-bromopyruvate
  • Anti-cancer chemotherapy
  • Gleevec
  • Glutathione
  • Multidrug resistance
  • Saccharomyces cerevisiae
  • Transport

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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