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

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

Research output: Contribution to journalArticle

124 Scopus citations

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 π in the yeast Saccharomyces cerevisiae. The expression of GST B1B1 or GST π 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 (US)
Pages (from-to)309-315
Number of pages7
JournalBiochemical Journal
Volume268
Issue number2
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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