Article

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

Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
Journal of Bioenergetics (Impact Factor: 3.21). 02/2012; 44(1):155-61. DOI: 10.1007/s10863-012-9421-8
Source: PubMed

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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    • "Jen1 was the first monocarboxylic acids transporter described in fungi (Casal et al. 1999). Besides its role in the uptake of lactate, pyruvate, acetate and propionate (Casal et al. 1999), it also transports the micronutrient selenite (McDermott et al. 2010) and the antitumor compound 3-bromopyruvate (Lis et al. 2012). The transport of the substrate is bidirectional, being Jen1 also involved in the acids efflux (van Maris et al. 2004; Pacheco et al. 2012). "
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