Open AccessReversal of Multidrug Resistance in Human Leukemia K562 by Tamolarizine, a Novel Calcium Antagonist
Author(s) -
Norihisa Miyake,
Reiko Fujita,
Masaaki Ishikawa,
Motowo Takayanagi,
Yoshio Takayanagi,
Kenichi Sasaki
Publication year - 2000
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.82.265
Subject(s) - k562 cells , p glycoprotein , efflux , doxorubicin , multiple drug resistance , pharmacology , cytotoxicity , antagonist , chemistry , cell culture , in vitro , leukemia , microbiology and biotechnology , chemotherapy , biology , receptor , biochemistry , immunology , medicine , antibiotics , genetics
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.