Reversal of multidrug resistance by novel cyclosporin A analogues and the cyclopeptolide SDZ 214-103 biosynthesized in vitro

K. Schwabe, G. Steinheider, A. Lawen, R. Traber, A. Hildebrandt

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7 Citations (Scopus)

Abstract

It was shown that cyclopeptolide SDZ 214-103 (10 μM) is more active in rhodamine-123 accumulation in actinomycin-d-resistant human lymphoma cells CCRF/ACTD400 than cyclosporin A (10 μM), but equipotent in the doxorubicin-resistant Friend erythroleukemia cell line F4-6/ADR. In F4-6/ADR cells, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed comparable cytotoxic effects of doxorubicin at various concentrations in the presence of SDZ 214-103 and cyclosporin A. For the other novel cyclosporin A analogues minor multidrug-resistance-modulating potency was demonstrated. At equipotent modulating doses of verapamil (10 μM) and cyclosporin A (10 μM) in the MTT assay regarding doxorubicin cytotoxicity, cyclosporin A was efficient in the rhodamine-123-uptake assay while verapamil was not active when identical incubation times were used.

Original languageEnglish
Pages (from-to)407-412
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Volume121
Issue number7
DOIs
Publication statusPublished - 1 Jul 1995

Keywords

  • Chemosensitizer
  • Cyclosporins
  • Multidrug resistance
  • Rhodamine-123

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