Glutathione and glutathione-dependent enzymes in cancer drug resistance

Lesley I. McLellan, C. Roland Wolf

    Research output: Contribution to journalReview article

    94 Citations (Scopus)

    Abstract

    Genetic and biochemical evidence has demonstrated that glutathione and glutathione-dependent enzymes play a central role in cellular defence against toxic environmental agents. Modulation of cellular glutathione homeostasis can also have a profound effect on the sensitivity of cancer cells to a wide range of drugs used in chemotherapy. These effects are produced by multifactorial mechanisms that involve inactivation of toxic electrophiles by conjugation, modulation of cellular redox state, activation of drug transporter systems and regulation of cell signalling and repair pathways. New data demonstrating the importance of these pathways in cytoprotection and greater understanding of the mechanisms which regulate their function reveal a number of new targets for novel anti-cancer agents. It is critical, however, if these targets are to be exploited correctly that the dynamics of glutathione regulation are taken into account.

    Original languageEnglish
    Pages (from-to)153-164
    Number of pages12
    JournalDrug Resistance Updates
    Volume2
    Issue number3
    DOIs
    Publication statusPublished - Jun 1999

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