Anticancer Effects of Phenoxazine Derivatives Revealed by Inhibition of Cell Growth and Viability, Disregulation of Cell Cycle, and Apoptosis Induction in HTLV-1-Positive Leukemia Cells
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概要
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Adult T-cell leukemia (ATL) is a malignant tumor of human CD4+ T cells infected with a human retrovirus, T lymphotropic virus type-1 (HTLV-1). The aim of the present study was to investigate the apoptotic effects of phenoxazines, 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one (Phx-1), 3-amino-1,4α-dihydro-4α,8-dimethyl-2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) on a T cell leukemia cell line from ATL patients, MT-1 cells; HTLV-1 transformed T-cell lines, HUT-102 cells and MT-2 cells; and an HTLV-1–negative rat sarcoma cell line, XC cells. Among these phenoxazines, Phx-3 at concentrations of less than 10 μg/ml extensively inhibited growth and cell viability; arrested cell cycles at sub G0/G1 phase; and augmented apoptosis of MT-1, HUT-102, and MT-2 cells. However, these phenoxazines did not affect the cell viability of an HTLV-1–negative rat sarcoma cell line, XC cells, and phytohemaggutinin-activated human peripheral blood mononuclear cells, although they markedly inhibited the growth of these cells. The transmission of HTLV-1 from HTLV-1–positive cells (MT-2 cells) to HTLV-1–negative cells (XC cells) was considered to be prevented by Phx-1, Phx-2, or Phx-3 because the syncytium formation between these cells was inhibited markedly in the presence of these phenoxazines. The present results suggest that Phx-1, Phx-2, and, in particular, Phx-3 may be useful as therapeutic agents against ATL, which is extremely refractory to current therapies.
- 2009-05-20
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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ENDO Takahiko
Department of Physics,Faculty of Science and Technology,Keio University
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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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MIYANO KUROSAKI
Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology
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IKEGAMI Kou
Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology
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KUROSAKI Kunihiko
Department of Legal Medicine, School of Medicine, Toho University
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AOYAGI Hoshimi
Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology
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HANAMI Mari
Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology
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YASUMOTO Jun
Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology
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MIYANO-KUROSAKI Naoko
Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology
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Endo Takahiko
Department Of Fermentation Tachnology Faculty Of Engineering Hiroshima University
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Kurosaki Kunihiko
Department Of Forensic Medicine Tokyo Medical University
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Hanami Mari
Department Of Life And Environmental Sciences Faculty Of Engineering Chiba Institute Of Technology
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Ikegami Kou
Department Of Life And Environmental Sciences Faculty Of Engineering Chiba Institute Of Technology
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Yasumoto Jun
Department Of Life And Environmental Sciences Faculty Of Engineering Chiba Institute Of Technology
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Aoyagi Hoshimi
Department Of Life And Environmental Sciences Faculty Of Engineering Chiba Institute Of Technology
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Miyano Kurosaki
Department Of Life And Environmental Sciences Faculty Of Engineering Chiba Institute Of Technology
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Miyano Kurosaki
Department Of Life And Environmental Science Chiba Institute Of Technology
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Kurosaki Kunihiko
Department Of Legal Medicine School Of Medicine Toho University
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