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

K Tsukahara1, T Watanabe, N Hata-Sugi

  • 1Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan. k-tsukahara@hhc.eisai.co.jp

Molecular Pharmacology
|November 28, 2001
PubMed

Insights

The anticancer drug E7070 inhibits amino acid and uracil uptake in yeast cells. Supplementing nutrients or enhancing transporter genes rescues growth, suggesting transporters are E7070 targets.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Yeast Genetics

Background:

  • E7070 is a novel sulfonamide anticancer agent.
  • Its precise molecular targets in mammalian cells remain unknown.
  • Fission yeast (Schizosaccharomyces pombe) was utilized as a model organism to identify E7070's targets.

Purpose of the Study:

  • To identify the molecular targets of the anticancer agent E7070.
  • To investigate the mechanism of E7070's action in Schizosaccharomyces pombe.

Main Methods:

  • Assessing the effect of E7070 on nutrient import in S. pombe.
  • Evaluating the sensitivity of auxotrophic yeast strains to E7070.
  • Investigating the impact of nutrient supplementation and transporter gene overexpression on E7070-induced growth inhibition.

Main Results:

  • E7070 was found to inhibit the import of amino acids and uracil in S. pombe.
  • Leucine- and uracil-auxotrophic strains exhibited sensitivity to E7070, with impaired proliferation in low-glucose medium.
  • The addition of leucine or uracil, or overexpression of transporter genes, rescued the growth inhibition.

Conclusions:

  • The study suggests that amino acid and uracil transporters are likely molecular targets of E7070 in S. pombe.
  • This finding provides insights into the mechanism of action of this novel anticancer agent.

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