Transport Mechanisms of Anthracycline Derivatives in Human Leukemia Cell Lines : Uptake of Pirarubicin, Daunorubicin and Doxorubicin by K562 and Multidrug-Resistant K562/ADM Cell
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概要
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We studied the uptake mechanisms of anthracycline derivatives, pirarubicin (THP), daunorubicin (DNR) and doxorubicin (ADR), in K562 and multidrug-resistant K562/ADM cells, which overexpress a multidrug efflux pump P-glycoprotein (P-gp). The uptake of THP, DNR and ADR by K562 or K562/ADM cells was time-, tetmperature- and concentration-dependent. The THP and ADR uptake by the parental cells was not affected by treatment with 4 mM 2,4-dinitrophenol (DNP) alone or DNP plus a P-gp specific inhibitor, cyclosporin A (CyA, 10 μM), while the DNR uptake in the DNP treatment group was significantly greater than that in the control group. These was no difference in the uptake of THP between DNP-pretreated K562 cells and DNP plus CyA-pretreated K562/ADM cells. The uptake of DNR or ADR was almost equal in both types of cell treated with DNP alone. Every kinetic constant for THP, DNR and ADR uptake by the sensitive cells was approximately equal to that in the resistant cells, respectively, under the above conditions. THP uptake was noncompetitively inhibited and stimulated on simultaneous treatment and preloading, respectively, of DNR or ADR in each type of cell. ADR showed noncompetitive inhibition of DNR uptake by either type of cell. Therefore, it was suggested that a common carrier-mediated transport system was involved in the uptake of THP, DNR and ADR, and that their binding sites in the carrier might be different from one another in both K562 and K562/ADM cells.
- 公益社団法人日本薬学会の論文
- 1996-07-15
著者
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Ohnishi N
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Kimura T
Kobe University Graduate School Of Medicine
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Takara Kohji
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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OHNISHI Noriaki
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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YOKOYAMA Teruyoshi
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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Takara Kohji
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Takara Kohji
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Takara Kohji
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Yagami Tatsurou
2shionogi Research Laboratories Shionogi & Co. Ltd.
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NAGASAWA Kazuki
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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Yokoyama T
Kitasato Univ. Sagamihara Jpn
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Yokoyama Teruyoshi
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Ohnishi Noriaki
Department Of Applied Fine Chemistry Faculty Of Engineering Osaka University
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NOMIYAMA MASAKO
Department of Hospital Pharmacy, Kyoto Pharmaceutical University
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Nagasawa Kazuki
Institute Of Molecular And Cellular Biosciences The University Of Tokyo
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Nagasawa Kazuki
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Nagasawa Kazuki
Department Of Environmental Biochemistry Kyoto Pharmaceutical University
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Nomiyama Masako
Department Of Hospital Pharmacy Kyoto Pharmaceutical University
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Koishi Tomokazu
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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