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

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

Norihisa Miyake1,2, Ryousuke Fujita2, Masaaki Ishikawa2,*, Motoaki Takayanagi2,
Yoshio Takayanagi2 and Ken-ichi Sasaki2

1Medical╩Information Department and Planning & Investigation Department, Nippon Chemiphar Co., Ltd.,
2-3, 2-chome, Iwamoto-cho Chiyoda-ku, Tokyo 101-8678, Japan
2Department╩of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical University,
4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
*╩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╩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

Copyrightę The Japanese Pharmacological Society 2000

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