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. Epub 2012 Feb 23.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / metabolism
  • Antineoplastic Agents, Alkylating / pharmacokinetics*
  • Antineoplastic Agents, Alkylating / toxicity*
  • Buthionine Sulfoximine / pharmacology
  • Glutathione / metabolism
  • Microbial Sensitivity Tests
  • Monocarboxylic Acid Transporters / metabolism
  • Pyruvates / metabolism
  • Pyruvates / pharmacokinetics*
  • Pyruvates / toxicity*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Symporters / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • JEN1 protein, S cerevisiae
  • Monocarboxylic Acid Transporters
  • Pyruvates
  • Saccharomyces cerevisiae Proteins
  • Symporters
  • Buthionine Sulfoximine
  • bromopyruvate
  • Glutathione