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

  • J Bioenerg Biomembr. 2012 Feb;44(1):155-61. doi: 10.1007/s10863-012-9421-8.
Paweł Lis  1 ,  Marek Zarzycki ,  Young H Ko ,  Margarida Casal ,  Peter L Pedersen ,  Andre Goffeau ,  Stanisław Ułaszewski
Affiliations
  • 1. Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
PMID: 22359102 DOI: 10.1007/s10863-012-9421-8
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.

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