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

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.
AuthorsL Slater, P Sweet, M Wetzel, M Stupecky, K Osann
JournalLeukemia research (Leuk Res) Vol. 19 Issue 8 Pg. 543-8 (Aug 1995) ISSN: 0145-2126 [Print] ENGLAND
PMID7658700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cyclosporins
  • valspodar
  • cremophor EL
  • Etoposide
  • Cyclosporine
  • Verapamil
  • Glycerol
  • 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)

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