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Novobiocin modulates colchicine sensitivity in parental and multidrug-resistant B16 melanoma cells.

Abstract
The effect of the antibiotic agent novobiocin on the sensitivity of melanoma cells to colchicine and vinblastine was examined in drug-sensitive and drug-resistant B16 melanoma cells. A cell line COL/R was selected for colchicine resistance. The COL/R cell line (resistant to 80 ng/ml colchicine) was found to possess the multidrug-resistant (MDR) phenotype. The cells were shown to be cross-resistant to vinblastine and Adriamycin and to overexpress P glycoprotein. P glycoprotein activity was assessed by using the rhodamine 123 accumulation test. Rhodamine accumulation was markedly decreased in COL/R cells as compared to the parental B16 cells. Verapamil reversed drug resistance and increased rhodamine accumulation in COL/R cells. Novobiocin in combination with colchicine or vinblastine synergistically inhibited the proliferation of parental B16 cells. In COL/R cells, novobiocin markedly decreased colchicine resistance and increased rhodamine accumulation. These data show that novobiocin increases the sensitivity of both parental and MDR melanoma cells to microtubule-disrupting cytotoxic drugs.
AuthorsJ Nordenberg, J Kornfeld, L Wasserman, M Shafran, E Halabe, E Beery, O Landau, A Novogrodsky, Y Sidi
JournalJournal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 120 Issue 10 Pg. 599-604 ( 1994) ISSN: 0171-5216 [Print] Germany
PMID7929531 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimetabolites, Antineoplastic
  • Rhodamines
  • Novobiocin
  • Rhodamine 123
  • Vinblastine
  • Verapamil
  • Colchicine
Topics
  • Animals
  • Antimetabolites, Antineoplastic (metabolism)
  • Cell Division (drug effects)
  • Cell Line
  • Clone Cells
  • Colchicine (toxicity)
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple
  • Melanoma, Experimental
  • Mice
  • Novobiocin (pharmacology)
  • Phenotype
  • Rhodamine 123
  • Rhodamines (metabolism)
  • Tumor Cells, Cultured
  • Verapamil (pharmacology)
  • Vinblastine (toxicity)

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