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Yeast as a biosensor of detoxification: a tool for identifying new compounds that revert multidrug resistance

Carmen Martín-Cordero1, Angeles Sanchez-Pico, Antonio J Leon-Gonzalez

  • 1Centro Andaluz de Biologia del Desarrollo, Universidad Pablo de Olavide-Consejo Superior de Investigaciones Cientificas, Junta de Andalucia Ctra. Utrera Km1 41013 Sevilla, Spain. rroddag@upo.es

Current Drug Targets
|April 26, 2013
PubMed

Insights

Multidrug resistance (MDR) in cancer is a major challenge. Researchers propose using fission yeast as a cost-efficient biosensor to screen for new compounds that can inhibit ATP-binding cassette (ABC) transporters, potentially overcoming chemotherapy resistance.

Area of Science:

  • Cancer Biology
  • Molecular Pharmacology
  • Microbiology

Background:

  • Tumor progression involves genetic changes leading to increased malignancy, including chemotherapy resistance.
  • ATP-binding cassette (ABC) transporters confer multidrug resistance (MDR) by extruding anticancer drugs from cells.
  • Existing strategies to inhibit ABC transporters have limited clinical success, necessitating novel approaches.

Purpose of the Study:

  • To introduce a novel, cost-efficient biosensor system for identifying inhibitors of ABC transporters.
  • To leverage fission yeast, Schizosaccharomyces pombe, as a tool for screening natural compounds and chemical libraries.
  • To discover molecules capable of reverting the multidrug resistant phenotype.

Main Methods:

  • Utilizing Schizosaccharomyces pombe as a detoxification biosensor.
  • Screening natural compounds and chemical libraries for MDR-reverting activity.
  • Employing established fission yeast genetic, biochemical, and cell biological analysis tools.

Main Results:

  • Demonstrated the potential of fission yeast as a biosensor for ABC transporter activity.
  • Identified a strategy for cost-efficient screening of potential MDR reversal agents.
  • Facilitated the identification of novel drug targets within the ABC transporter family.

Conclusions:

  • Fission yeast offers a powerful and economical platform for discovering new ABC transporter inhibitors.
  • This approach can accelerate the development of compounds to combat multidrug resistance in cancer therapy.
  • Combining identified inhibitors with chemotherapy may improve treatment outcomes for multidrug-resistant tumors.

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