Anticancer agent E7070 inhibits amino acid and uracil transport in fissionyeast

E7070 is a novel sulfonamide anticancer agent that inhibits cell cycle prog ression in G(1) in mammalian cells, but its action targets are not known. W e recently employed the genetically amenable fission yeast Schizosaccharomy ces pombe as a model organism to search for its targets. Here, we show that E7070 inhibits imports of amino acid and uracil into S. pombe cells. Unlik e their prototrophic counterparts, leucine- and uracil-auxotrophic strains are sensitive to E7070 and are unable to proliferate with a delayed G(1)-S transition in low-glucose yeast extract-polypeptone medium containing this drug because this chemical markedly inhibits the uptake of leucine and urac il in low glucose medium. Furthermore, addition of leucine or uracil to the culture medium or overexpression of genes encoding an amino acid or uracil transporter suppresses the E7070-imposed growth inhibition of these auxotr ophic strains. Thus, some of the molecular targets for E7070 action in S. p ombe are likely to be leucine and uracil transporters.