Apoptosis Induction Preceded by Mitochondrial Depolarization in Multiple Myeloma Cell Line U266 by 2-Aminophenoxazine-3-one(Medicinal Chemistry)
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概要
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The aim of the present study was to investigate the mechanism of apoptosis in human multiple myeloma cell line, U266, caused by 2-aminophenoxazine-3-one (Phx-3). Flow-cytometrical and morphological analyses showed that Phx-3 increased the population of annexin V -positive cells including early stage apoptotic cells and late stage apoptotic cells and induced DNA fragmentation or apoptotic body formation in U266 cells, indicating that Phx-3 induced the apoptosis of U266 cells. Activity of caspase-3 was extensively increased in U266 cells treated with Phx-3 time-dependently within 24 h, but this Phx-3-stimulated activity of the enzyme in the cells was completely cancelled by the addition of N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), a pan-caspase inhibitor. The addition of z-VAD-fmk almost blocked the apoptotic effect of Phx-3 against U266 cells, indicating that Phx-3-induced apoptosis of U266 cells was dependent on a caspase signaling pathway. Moreover, the apoptosis of U266 cells occurred after the induction of cell cycle arrest of the cells in the S and G_2/M phase, the loss of mitochondrial membrane potential, and activation of caspase-3 reached maximum, which were caused by Phx-3 within 24h. These results support the views that the apoptosis of U266 cells caused by Phx-3 may be preceded by the cell cycle arrest, depolarization of mitochondria and activation of caspase-3. These results support the view that Phx-3 may be utilized in future as chemotherapeutic agent against multiple myeloma which is extremely refractory to chemotherapy.
- 社団法人日本薬学会の論文
- 2008-01-01
著者
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Tomoda Akio
Department of Biochemistry and Intractable Immune System Disease Research Center, Tokyo Medical Univ
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IMAIZUMI Kazuhiko
Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University
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CHE Xiao-Fang
Department of Cancer Chemotherapy, Institute for Cancer Research Kagoshima University
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AKIYAMA Shinichi
Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine, Kagoshima Uni
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Mizuguchi Junichiro
Department of Immunology, Tokyo Medical University
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Che Xiao-fang
Department Of Molecular Oncology Graduate School Of Medicine Kagoshima University
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Che Xiao-fang
Department Of Cancer Chemotherapy Institute For Cancer Research Kagoshima University
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Tomoda A
Tokyo Medical Univ.
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Tomoda Akio
Dep. Of Biochemistry Tokyo Medical Univ. Jpn
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Tomoda Akio
Department Of Biochemistry And Intractable Tokyo Medical University
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Tomoda Akio
Department Of Biochemistry And Intractable Immune System Disease Research Center Tokyo Medical Unive
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SHIRATO Ken
Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University
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MIYAZAWA Keisuke
First Department of Internal Medicine, Tokyo Medical University
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TAKASAKI Akira
Department of Geriatric Medicine, Tokyo Medical University
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Miyazawa Keisuke
First Department Of Internal Medicine Tokyo Medical University
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Mizuguchi Junichiro
Department Of Immunology Graduate School Of Medicine Kagoshima University
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Shirato Ken
Laboratory Of Physiological Sciences Faculty Of Human Sciences Waseda University
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Shirato Ken
Laboratory Of Physiological Sciences Graduate School Of Human Sciences Waseda University
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Takasaki Akira
Department Of Geriatric Medicine Tokyo Medical University
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Akiyama Shinichi
Department Of Molecular Oncology Graduate School Of Medicine Kagoshima University
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Akiyama Shinichi
Department Of Biochemistry And Surgery Oita Medical School
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Imaizumi Kazuhiko
Laboratory Of Physiological Sciences Faculty Of Human Sciences Waseda University
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Miyazawa Keisuke
Department Of Biochemistry Kyushu University Graduate School Of Medical Sciences
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Che Xiao-fang
Department Of Biochemistry Tokyo Medical University
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Imaizumi Kazuhiko
Laboratory Of Physiological Sciences School Of Human Sciences Waseda University
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