Monensin and verapamil do not alter intracellular localisation of daunorubicin in multidrug resistant human KB cells.
The effects of monensin, verapamil and several inhibitors of membrane transport processes on the accumulation of [3H] daunorubicin by human KB-A1 cells have been investigated to determine the role of subcellular vesicular transport in the multidrug resistance phenotype. The Golgi inhibitor, brefeldin A, had no effect on drug accumulation, which suggests that vesicular transport is not a significant factor in drug resistance in these cells. KB-A1 cells were collaterally sensitive to both monensin and verapamil. Both of these compounds reduced drug efflux but did not alter subcellular distribution of daunorubicin, consistent with the view that monensin, like verapamil, acts directly on P-glycoprotein.
Wood
D J
DJ
Department of Biology, University of York, UK.
Rumsby
M G
MG
Warr
J R
JR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology; D003630:Daunorubicin / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005089:Exocytosis / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D007624:KB Cells / Q000187:drug effects* / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D013347:Subcellular Fractions / Q000737:chemistry; D014700:Verapamil / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002121:Calcium Channel Blockers; D003517:Cyclopentanes; D007476:Ionophores; D009363:Neoplasm Proteins; D020126:Brefeldin A; D008985:Monensin; D014700:Verapamil; D003630:Daunorubicin