title: Anticancer agent E7070 inhibits amino acid and uracil transport in fission yeast.
abstract: 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.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan. k-tsukahara@hhc.eisai.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Tsukahara
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Hata-Sugi
authors.forename: K
authors.initials: K
authors.lastname: Yoshimatsu
authors.forename: H
authors.initials: H
authors.lastname: Okayama
authors.forename: T
authors.initials: T
authors.lastname: Nagasu
mesh_terms: D026905:Amino Acid Transport Systems / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003470:Culture Media; D025141:Drug Resistance, Fungal / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D014498:Uracil / Q000378:metabolism*
chemical_list: D026905:Amino Acid Transport Systems; D000970:Antineoplastic Agents; D003470:Culture Media; C439829:N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide; D013449:Sulfonamides; D014498:Uracil; D007930:Leucine; D005947:Glucose