Reversal of Acquired Resistance to Doxorubicin in K562 Human Leukemia Cells by Astemizole

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概要

• 論文の詳細を見る

• This study demonstrates that astemizole, a non-sedating anti-histaminergic drug low toxicity in vivo, greatly potentiates the growth-inhibitory activity of doxorubicin in doxorubicin-resistant human leukemia cells (K562/DXR). Astemizole synergistically potentiated the cytotoxicity of doxorubicin for K562/DXR cells at a concentration of 0.1-3 μM in a dose- dependent manner, whereas they showed hardly any synthergistic effect in the parental cell line (K562) at the same concentration. Since doxorubicin resistance in these cells is associated with the expression of high levels of P-glycoprotein, we evaluated the effect of astemizole on P-glycoprotein activity in cytoflurographic efflux experiments with doxorubicin. Our results indicate that astemizole inhibits the P-glycoprotein pump-efflux activity in a dose-related manner. moreover, it also inhibits the photolabeling of P-glycoprotein by [^3H]azidopine in a dose-dependent manner. These findings provide a biological basis for the potential therapeutic application of astemizole as an anticancer drug either alone or in combination with doxorubicin to multidrug-resistant leukemic cells.

• 社団法人日本薬学会の論文
• 2000-01-01

著者

• ISHIKAWA Masaaki

  Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi

• TAKAYANAGI Motoaki

  Department of Pathophysiology, Tohoku Pharmaceutical University

• Sasaki K

  Dep. Of Pharmacology And Toxicology Cancer Res. Inst. Tohoku Pharmaceutical Univ.

• Takayanagi M

  Department Of Pathophysiology Tohoku Pharmaceutical University

• Takayanagi Motoaki

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Takayanagi Motoaki

  Cancer Research Institute Tohoku Pharmaceutical University

• FUJITA Ryousuke

  Department of pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi

• SASAKI Ken-ichi

  Department of pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi

• TAKAYANAGI Yoshio

  Department of Pharmacology and Toxicology, Cancer Research Institite, Tohoku Phamaceutical Universit

• Ishikawa Masaaki

  東北薬科大学癌研究所

• Ishikawa Masaaki

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku College Of Pharmacy

• Takayanagi Y

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Kanno Shu-ichi

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• SASAKI Kenichi

  Cancer Research Institute, Tohoku College of Pharmacy

• Sasaki Ken-ichi

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Sasaki Ken-ichi

  Department Of Pathology Sapporo Medical University School Of Medicine

• Fujita Ryousuke

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Sasaki Ken-ichi

  Department Of Chemistry Faculty Of Science Hiroshima University

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