Comparison of cyclosporin A, verapamil, PSC-833 and cremophor EL as enhancing agents of VP-16 in murine lymphoid leukemias.

Abstract

Although verapamil, cyclosporin A. cremophor EL and PSC-833 are active as multidrug resistance modulators, there has been limited study of these compounds as possible chemotherapy enhancing agents against drug-sensitive tumors. We compared these agents as modifiers of VP-16 cytotoxicity in vitro and modifiers of VP-16 efficacy in vivo against drug-sensitive P388 and L1210 leukemias. Our study indicates that cyclosporin A enhances VP-16 cytotoxicity to a significantly greater extent than equimolar concentrations of verapamil or PSC-833. Although cremophor EL shows significantly greater activity than verapamil in VP-16 cytotoxicity enhancement in vitro, it is ineffective when added to VP-16 therapy of mice bearing L1210 leukemia.

• Authors: L Slater, P Sweet, M Wetzel, M Stupecky, K Osann
• Journal: Leukemia research (Leuk Res) Vol. 19 Issue 8 Pg. 543-8 (Aug 1995) ISSN: 0145-2126 [Print] England
• PMID: 7658700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclosporins
• cremophor EL
• Etoposide
• Cyclosporine
• Verapamil
• Glycerol
• valspodar

Topics

• Animals
• Cell Survival (drug effects)
• Cyclosporine (administration & dosage)
• Cyclosporins (administration & dosage)
• Drug Synergism
• Etoposide (administration & dosage)
• Glycerol (administration & dosage, analogs & derivatives)
• Leukemia L1210
• Leukemia P388
• Mice
• Survival Analysis
• Tumor Cells, Cultured
• Verapamil (administration & dosage)