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. © 2000 Cancer Research Campaign
Keywords: glutathione, ZD2767, ADEPT, alkylating agent, buthionine sulfoximine
Full Text
The Full Text of this article is available as a PDF (49.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alaoui-Jamali M. A., Panasci L., Centurioni G. M., Schecter R., Lehnert S., Batist G. Nitrogen mustard-DNA interaction in melphalan-resistant mammary carcinoma cells with elevated intracellular glutathione and glutathione-S-transferase activity. Cancer Chemother Pharmacol. 1992;30(5):341–347. doi: 10.1007/BF00689960. [DOI] [PubMed] [Google Scholar]
- Blakey D. C., Burke P. J., Davies D. H., Dowell R. I., East S. J., Eckersley K. P., Fitton J. E., McDaid J., Melton R. G., Niculescu-Duvaz I. A. ZD2767, an improved system for antibody-directed enzyme prodrug therapy that results in tumor regressions in colorectal tumor xenografts. Cancer Res. 1996 Jul 15;56(14):3287–3292. [PubMed] [Google Scholar]
- Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
- Cotgreave I. A., Moldéus P. Methodologies for the application of monobromobimane to the simultaneous analysis of soluble and protein thiol components of biological systems. J Biochem Biophys Methods. 1986 Nov;13(4-5):231–249. doi: 10.1016/0165-022x(86)90102-8. [DOI] [PubMed] [Google Scholar]
- Friedman H. S., Dolan M. E., Kaufmann S. H., Colvin O. M., Griffith O. W., Moschel R. C., Schold S. C., Bigner D. D., Ali-Osman F. Elevated DNA polymerase alpha, DNA polymerase beta, and DNA topoisomerase II in a melphalan-resistant rhabdomyosarcoma xenograft that is cross-resistant to nitrosoureas and topotecan. Cancer Res. 1994 Jul 1;54(13):3487–3493. [PubMed] [Google Scholar]
- Hall A. G., Tilby M. J. Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies. Blood Rev. 1992 Sep;6(3):163–173. doi: 10.1016/0268-960x(92)90028-o. [DOI] [PubMed] [Google Scholar]
- Hayes J. D., Wolf C. R. Molecular mechanisms of drug resistance. Biochem J. 1990 Dec 1;272(2):281–295. doi: 10.1042/bj2720281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skehan P., Storeng R., Scudiero D., Monks A., McMahon J., Vistica D., Warren J. T., Bokesch H., Kenney S., Boyd M. R. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990 Jul 4;82(13):1107–1112. doi: 10.1093/jnci/82.13.1107. [DOI] [PubMed] [Google Scholar]
- Smith C. V., Jones D. P., Guenthner T. M., Lash L. H., Lauterburg B. H. Compartmentation of glutathione: implications for the study of toxicity and disease. Toxicol Appl Pharmacol. 1996 Sep;140(1):1–12. doi: 10.1006/taap.1996.0191. [DOI] [PubMed] [Google Scholar]
- Springer C. J., Dowell R., Burke P. J., Hadley E., Davis D. H., Blakey D. C., Melton R. G., Niculescu-Duvaz I. Optimization of alkylating agent prodrugs derived from phenol and aniline mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme prodrug therapy (ADEPT). J Med Chem. 1995 Dec 22;38(26):5051–5065. doi: 10.1021/jm00026a013. [DOI] [PubMed] [Google Scholar]