Phenoxazine Derivatives 2-Amino-4,4α-dihydro-4α-phenoxazine-3-one and 2-Aminophenoxazine-3-one-Induced Apoptosis through a Caspase-Independent Mechanism in Human Neuroblastoma Cell Line NB-1 Cells(Medicinal Chemistry)
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概要
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The aim of the present study was to determine whether phenoxazines such as 2-amino-4,4-α-dihydro-4α-phenoxazine-3-one (Phx-1) and 2-aminophenoxazine-3-one (Phx-3) may suppress the proliferation of human neuroblastoma cell line, NB-1 that is refractory to chemotherapeutic agents, inducing apoptosis through the activation of caspase pathway or not. Phx-1 and Phx-3 suppressed the proliferation of NB-1 cells extensively dependent on dose and time. The IC_<50> of Phx-1 and Phx-3 was about 20μM and 0.5μM, respectively, when the cells were treated with Phx-1 or Phx-3 for 72h. Phx-1 and Phx-3 caused the mixed types of cell death-apoptosis and necrosis-in NB-1 cells, which was detected by flow cytometry. The induction of apoptosis/necrosis caused by these phenoxazines seemed to be correlated dominantly with the caspase independent pathway, because the increased activity of effector caspase 3/7 in NB-1 cells caused by 50μM Phx-1 or 20μM Phx-3 was completely cancelled by the addition of z-VAD-fmk, a pan-caspase inhibitor, but such phenoxazines-suppressed viability of NB-1 cells was not recovered to normal levels by this inhibitor. The results of this study demonstrate that Phx-1 and Phx-3 have antitumor activity against the neuroblastoma cell line, NB-1, though the IC_<50> was extremely low for Phx-3, inducing the mixed types of cell death, apoptosis and necrosis, caspase-independently.
- 社団法人日本薬学会の論文
- 2007-02-01
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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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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ABE Akihisa
Department of Biochemistry, Tokyo Medical University
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Abe Akihisa
Department Of Biochemistry Tokyo Medical College
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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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Imaizumi Kazuhiko
Laboratory Of Physiological Sciences Faculty Of Human Sciences Waseda University
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Imaizumi Kazuhiko
Laboratory Of Physiological Sciences School Of Human Sciences Waseda University
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