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

Abstract
It was shown that cyclopeptolide SDZ 214-103 (10 microM) is more active in rhodamine-123 accumulation in actinomycin-D-resistant human lymphoma cells CCRF/ACTD400 than cyclosporin A (10 microM), 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 microM) and cyclosporin A (10 microM) 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.
AuthorsK Schwabe, G Steinheider, A Lawen, R Traber, A Hildebrandt
JournalJournal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 121 Issue 7 Pg. 407-12 ( 1995) ISSN: 0171-5216 [Print] Germany
PMID7635870 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Cyclosporins
  • Immunosuppressive Agents
  • Rhodamines
  • Tetrazolium Salts
  • Thiazoles
  • SDZ 214-103
  • Dactinomycin
  • Rhodamine 123
  • Doxorubicin
  • thiazolyl blue
Topics
  • Cyclosporins (biosynthesis, pharmacology)
  • Dactinomycin (pharmacology)
  • Doxorubicin (pharmacology)
  • Drug Interactions
  • Drug Resistance, Microbial (physiology)
  • Drug Resistance, Multiple
  • Drug Screening Assays, Antitumor
  • Friend murine leukemia virus
  • Humans
  • Immunosuppressive Agents (pharmacology)
  • Leukemia, Erythroblastic, Acute (drug therapy, metabolism, virology)
  • Lymphoma (drug therapy, metabolism)
  • Rhodamine 123
  • Rhodamines (pharmacokinetics)
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Cells, Cultured (drug effects)

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