Reversal of multidrug resistance in human leukemia K562 by tamolarizine, a novel calcium antagonist.
A new type of organic Ca2+ channel blocker, tamolarizine, was examined for its reversing effect on multidrug-resistant tumor cells. Tamolarizine synergistically potentiated the cytotoxicity of doxorubicin for doxorubicin-resistant K562 cells (K562/DXR) at a concentration of 0.1-10 microM, but had hardly any synergistic effects in the parental cell line (K562) at the same concentration. Moreover, tamolarizine inhibits the P-glycoprotein pump-efflux activity in a dose-related manner and reduces the expression of the immunoreactive P-glycoprotein in K562/DXR cells as evaluated by cytofluorimetric assay. These results indicate that tamolarizine reverses the multidrug-resistance phenotype through direct interaction with P-glycoprotein.
Miyake
N
N
Medical Information Department, Nippon Chemiphar Co., Ltd., Tokyo, Japan.
Fujita
R
R
Ishikawa
M
M
Takayanagi
M
M
Takayanagi
Y
Y
Sasaki
K
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D001386:Azides / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D020014:K562 Cells; D010879:Piperazines / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001386:Azides; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010879:Piperazines; C050134:tamolarizine; D020112:Rhodamine 123; C041130:azidopine; D004317:Doxorubicin