Reversal of Vinblastine Resistance in Human Leukemic Cells by Haloperidol and Dihydrohaloperidol
スポンサーリンク
概要
- 論文の詳細を見る
Haloperidol, an antipsychotic, was investigated in cells overexpressing P-glycoprotein to determine whether it was a clinically effective drug to reverse for reversing multidrug resistance(MDR)mediated by P-glycoprotein. A-nontoxic concentration of haloperidol(1-30μ_M)enhanced the cytotoxic effects of vinblastine(VBL)concentration-dependently in VBL-resistant human leukemia(K562/VBL)cells, but had no effect in the parent cells. Haloperidol also enhanced the cytotoxicities of epirubicin, doxorubicin and actinomycin D in the K562/VBL cells, but not those of idarubicin or cisplatin ; this enhancement was less than that of the VBL toxicity in the VBL-resistant tumor line. Haloperidol increased the intracelluar accumulation of VBL in the K562/VBL cells, and the binding of[H^3]-azidopine to the cell-surfase protein, P-glycoprotein, was inhibited by haloperidol in a concentration-dependent manner. Haloperidol was less potent than verapamil. Thus, haloperidol appeared to potentiate anticancer agents through the reversal of MDR by competitively inhibiting drug-binding to P-glycoprotein. In contrast, the main metabolite of haloperidol, dihydrohaloperidol, without antipsychotic activity, had less of an effect. Therefore, haloperidol might be useful in reversing drug-resistance.
- 社団法人日本薬学会の論文
- 2001-06-01
著者
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ISHIKAWA Masaaki
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi
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TAKAYANAGI Motoaki
Department of Pathophysiology, Tohoku Pharmaceutical University
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Sasaki K
Dep. Of Pharmacology And Toxicology Cancer Res. Inst. Tohoku Pharmaceutical Univ.
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Takayanagi M
Department Of Pathophysiology Tohoku Pharmaceutical University
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Takayanagi Motoaki
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Takayanagi Motoaki
Cancer Research Institute Tohoku Pharmaceutical University
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FUJITA Ryousuke
Department of pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi
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FURUSAWA Shinobu
Department of pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi
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SASAKI Ken-ichi
Department of pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi
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KATAOKA Yumi
Department of Phamacology and Pharmacy, Cancer Research Institute, Cancer Research Institute
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MIURA Masatomo
Department of Phamacology and Pharmacy, Cancer Research Institute
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TAKESHITA Mitsuhiro
Department of Phamacology and Pharmacy, Cancer Research Institute
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TAKAYANAGI Yoshio
Department of Pharmacology and Toxicology, Cancer Research Institite, Tohoku Phamaceutical Universit
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FURUSAWA Shinobu
Cancer Research Institute, Tohoku Pharmaceutical University
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Ishikawa Masaaki
東北薬科大学癌研究所
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Ishikawa Masaaki
Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University
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Ishikawa Masaaki
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Ishikawa Masaaki
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku College Of Pharmacy
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Takayanagi Y
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Kataoka Yumi
Department Of Phamacology And Pharmacy Cancer Research Institute Cancer Research Institute
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Kanno Shu-ichi
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Miura Masatomo
Department Of Phamacology And Pharmacy Cancer Research Institute
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SASAKI Kenichi
Cancer Research Institute, Tohoku College of Pharmacy
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Sasaki Ken-ichi
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Kataoka Yumi
Department Of Environmental Health Science Tohoku Pharmaceutical University
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Takeshita Mitsuhiro
Department Of Pharmacology Tohoku Pharmaceutical University
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Sasaki Ken-ichi
Department Of Pathology Sapporo Medical University School Of Medicine
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Fujita Ryousuke
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Sasaki Ken-ichi
Department Of Chemistry Faculty Of Science Hiroshima University
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