Novobiocin modulates colchicine sensitivity in parental and multidrug-resistant B16 melanoma cells.
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.
Nordenberg
J
J
Endocrinology Laboratory, Beilinson Medical Center, Petah Tiqva, Israel.
Kornfeld
J
J
Wasserman
L
L
Shafran
M
M
Halabe
E
E
Beery
E
E
Landau
O
O
Novogrodsky
A
A
Sidi
Y
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells; D003078:Colchicine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D008546:Melanoma, Experimental; D051379:Mice; D009675:Novobiocin / Q000494:pharmacology*; D010641:Phenotype; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000633:toxicity*
D000964:Antimetabolites, Antineoplastic; D012235:Rhodamines; D009675:Novobiocin; D020112:Rhodamine 123; D014747:Vinblastine; D014700:Verapamil; D003078:Colchicine