Vol. 60, Issue 6, 1254-1259, December 2001

Anticancer Agent E7070 Inhibits Amino Acid and Uracil Transport in Fission Yeast

Kappei Tsukahara, Tatsuo Watanabe, Naoko Hata-Sugi, Kentaro Yoshimatsu, Hiroto Okayama, and Takeshi Nagasu

Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan (K.T., T.W., N.H.-S., K.Y., T.N.); and Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan (H.O.)

E7070 is a novel sulfonamide anticancer agent that inhibits cell cycle progression in G₁ in mammalian cells, but its action targets are not known. We recently employed the genetically amenable fission yeast Schizosaccharomyces 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. Unlike their prototrophic counterparts, leucine- and uracil-auxotrophic strains are sensitive to E7070 and are unable to proliferate with a delayed G₁-S transition in low-glucose yeast extract-polypeptone medium containing this drug because this chemical markedly inhibits the uptake of leucine and uracil 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 auxotrophic strains. Thus, some of the molecular targets for E7070 action in S. pombe are likely to be leucine and uracil transporters.