Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drugs adriamycin and chlorambucil

S M Black, J D Beggs, J D Hayes, A Bartoszek, M Muramatsu, M Sakai, C R Wolf

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Abstract

Adaptation and resistance to chemicals in the environment is a critical part of the evolutionary process. As a result, a wide variety of defence systems that protect cells against chemical insult have evolved. Such chemical resistance mechanisms appear to play a central role in determining the sensitivity of human tumours to treatment with chemotherapeutic drugs. The glutathione S-transferases (GST) are important detoxification enzymes whose over-expression has been associated with drug-resistance. In order to evaluate this possibility we have expressed the human Alpha-class and Pi-class GST cDNAs that encode GST B1B1 and GST pi in the yeast Saccharomyces cerevisiae. The expression of GST B1B1 or GST pi resulted in a marked reduction in the cytotoxic effects of chlorambucil, a bifunctional alkylating agent, and an anthracycline, adriamycin. These data provide direct evidence that the over-expression of GST in cells can confer resistance to anticancer drugs.

Original languageEnglish
Pages (from-to)309-15
Number of pages7
JournalBiochemical Journal
Volume268
Issue number2
DOIs
Publication statusPublished - 1 Jun 1990

Keywords

  • Alkylating Agents/pharmacology
  • Chlorambucil/pharmacology
  • DNA, Fungal/biosynthesis
  • DNA, Recombinant/biosynthesis
  • Doxorubicin/pharmacology
  • Drug Resistance, Microbial
  • Escherichia coli/genetics
  • Gene Expression
  • Glutathione Transferase/biosynthesis
  • Microbial Sensitivity Tests
  • Saccharomyces cerevisiae/drug effects

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