Mechanism of Resistance to Oxidative Stress in Doxorubicin Resistant Cells
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概要
- 論文の詳細を見る
Doxorubicin (DOX) is an anthracycline drug widely used in chemotherapy for cancer patients, but it often gives rise to multidrug resistance in cancer cells. The purpose of this work was to study the effect of hydrogen peroxide in DOX-sensitive mouse P388/S leukemia cells and in the DOX-resistant cell line. Hydrogen peroxide induced a significant increase in dose- and time-response cell death in cultured P388/S cells. The degree of cell death in P388/DOX cells induced by hydrogen peroxide was less than that in P388/S cells treated with hydrogen peroxide. Parent cells exposed to 3 mM of hydrogen peroxide showed a loss of mitochondrial membrane potential correlated with cell death. Hydrogen peroxide at a concentration greater than 0.3 mM increased the intracellular Ca^2+ of P388/S cells dose-dependently ; however, no change following addition of hydrogen peroxide (0.3-1mM) was observed in the resistant cells. Hydrogen peroxide (0.1 and 1 mM) treatment also induced the production of intracellular ROS in P388/S cells, while no such increase was produced by this substance in P388/DOX cells. Resistant cells also showed a significant level of glutathione (GSH) compared with the parent cells. In addition, N-acetyl-L-cysteine and reduced GSH antioxidants abolished death of P388/S cells caused by hydrogen peroxide. Therefore, it is believed that the reduced effect of oxidative stress towards the resistant cells may be related to an increase in intracellular GSH level.
- 社団法人日本薬学会の論文
- 2001-05-01
著者
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Sakaguchi Shuhei
東北薬科大学 第一衛生化学
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Sakaguchi Shuhei
First Department Of Hygienic Chemistry Tohoku Pharmaceutical University
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Satoh S
Department Of Pharmacology And Pharmacotherapy Nihon Pharmaceutical University
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Satoh Susumu
Nagasaki Institute Of Applied Science
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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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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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TAKAYANAGI Yoshio
Department of Pharmacology and Toxicology, Cancer Research Institite, Tohoku Phamaceutical Universit
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KIMURA Etsuko
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi
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KISARA Satoko
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi
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NAKANO Shinya
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi
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MURATA Ryo
First Department of Pharmaceutics, Tohoku Pharmaceutical University
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TANAKA Yorihisa
First Department of Pharmaceutics, Tohoku Pharmaceutical University
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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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Tanaka Y
Kyushu Univ. Fukuoka Jpn
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Kimura E
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Takayanagi Y
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Murata R
First Department Of Pharmaceutics Tohoku Pharmaceutical University
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Kisara Satoko
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Kanno Shu-ichi
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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SASAKI Kenichi
Cancer Research Institute, Tohoku College of Pharmacy
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Tanaka Y
Toho Univ. School Of Pharmaceutical Sci. Chiba Jpn
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Tanaka Yorihisa
Department Of Drug Metabolism And Pharmacokinetics Tohoku Pharmaceutical University
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Sasaki Ken-ichi
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Nakano S
Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University
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Sasaki Ken-ichi
Department Of Pathology Sapporo Medical University School Of Medicine
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Sasaki Ken-ichi
Department Of Chemistry Faculty Of Science Hiroshima University
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Tanaka Yoshitaka
Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University
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Sakaguchi Shuhei
First Department of Hygienic Chemistry ; Tohoku Pharmaceutical University
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