Anticancer agent E7070 inhibits amino acid and uracil transport in fission yeast. 2001

K Tsukahara, and T Watanabe, and N Hata-Sugi, and K Yoshimatsu, and H Okayama, and T Nagasu
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan. k-tsukahara@hhc.eisai.co.jp

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.

UI MeSH Term Description Entries
D007930 Leucine An essential branched-chain amino acid important for hemoglobin formation. L-Leucine,Leucine, L-Isomer,L-Isomer Leucine,Leucine, L Isomer
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D012568 Schizosaccharomyces A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales. Fission Yeast,Schizosaccharomyces malidevorans,Schizosaccharomyces pombe,Yeast, Fission,S pombe,Fission Yeasts
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D014498 Uracil One of four nucleotide bases in the nucleic acid RNA.
D025141 Drug Resistance, Fungal The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation. Antibiotic Resistance, Fungal,Antifungal Drug Resistance,Resistance, Antifungal Drug
D026905 Amino Acid Transport Systems Cellular proteins and protein complexes that transport amino acids across biological membranes. Amino Acid Permeases,Amino Acid Transporters,Amino Acid Permease,Amino Acid Transporter,Permease, Amino Acid,Permeases, Amino Acid,Transporters, Amino Acid

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