Cellular glutathione as a determinant of the sensitivity of colorectal tumour cell-lines to ZD2767 antibody-directed enzyme prodrug therapy (ADEPT)

Br J Cancer. 2000 Jul;83(2):267-9. doi: 10.1054/bjoc.2000.1240.

Abstract

ZD2767P, a nitrogen mustard glutamate prodrug, is currently being evaluated in Phase 1 clinical trials of antibody directed enzyme prodrug therapy (ADEPT). There was no significant relationship between basal glutathione (GSH) concentration and sensitivity to ZD2767P + carboxpeptidase G2 (CPG2) in colorectal tumour cell-lines. Depletion of intracellular GSH using buthionine sulfoximine (BSO) resulted in only a modest potentiation of ZD2767P + CPG2 activity and hence BSO is unlikely to markedly enhance the activity of this ADEPT treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Cell Division / drug effects
  • Colorectal Neoplasms / pathology
  • Glutathione / metabolism*
  • HT29 Cells
  • Humans
  • Nitrogen Mustard Compounds / pharmacology*
  • Prodrugs / metabolism
  • Prodrugs / pharmacology*
  • Tumor Cells, Cultured
  • gamma-Glutamyl Hydrolase / metabolism*

Substances

  • Antineoplastic Agents, Alkylating
  • Nitrogen Mustard Compounds
  • Prodrugs
  • ZD 2767
  • gamma-Glutamyl Hydrolase
  • Glutathione