Jpn. J. Pharmacol. 82 (3), 265-268 (2000)

Reversal of Multidrug Resistance in Human Leukemia K562
by Tamolarizine, a Novel Calcium Antagonist

Norihisa Miyake^1,2, Ryousuke Fujita², Masaaki Ishikawa^2,*, Motoaki Takayanagi²,
Yoshio Takayanagi² and Ken-ichi Sasaki<sup>2


1</sup>MedicalﾊInformation Department and Planning & Investigation Department, Nippon Chemiphar Co., Ltd.,
2-3, 2-chome, Iwamoto-cho Chiyoda-ku, Tokyo 101-8678, Japan
²Departmentﾊof Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical University,
4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
*ﾊTo whom correspondence should be addressed.

Abstract: 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ﾊmM, 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.

Keywords: Doxorubicin-resistant K562 cell, Tamolarizine, Multidrug resistance