title: Transport and cytotoxicity of the anticancer drug 3-bromopyruvate in the yeast Saccharomyces cerevisiae.
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.
authors.affiliation: Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Lis
authors.forename: Marek
authors.initials: M
authors.lastname: Zarzycki
authors.forename: Young H
authors.initials: YH
authors.lastname: Ko
authors.forename: Margarida
authors.initials: M
authors.lastname: Casal
authors.forename: Peter L
authors.initials: PL
authors.lastname: Pedersen
authors.forename: Andre
authors.initials: A
authors.lastname: Goffeau
authors.forename: Stanisław
authors.initials: S
authors.lastname: Ułaszewski
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D027981:Symporters / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; C118697:JEN1 protein, S cerevisiae; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters; D019328:Buthionine Sulfoximine; C017092:bromopyruvate; D005978:Glutathione