Cellular glutathione as a determinant of the sensitivity of colorectal tumour cell-lines to ZD2767 antibody-directed enzyme prodrug therapy (ADEPT).
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.
Monks
N R
NR
Cancer Research Unit, University of Newcastle upon Tyne, UK.
Calvete
J A
JA
Curtin
N J
NJ
Blakey
D C
DC
East
S J
SJ
Newell
D R
DR
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D011623:gamma-Glutamyl Hydrolase / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D009588:Nitrogen Mustard Compounds; D011355:Prodrugs; C097602:ZD 2767; D011623:gamma-Glutamyl Hydrolase; D005978:Glutathione