8-Aminoadenosine Enhances Radiation-induced Cell Death in Human Lung Carcinoma A549 Cells
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- MEIKE Shunsuke
- Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- YAMAMORI Tohru
- Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- YASUI Hironobu
- Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- EITAKI Masato
- Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- MATSUDA Akira
- Laboratory of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University
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- INANAMI Osamu
- Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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抄録
The combination of a chemotherapeutic agent and radiation is widely applied to enhance cell death in solid tumor cells in cancer treatment. The purine analogue 8-aminoadenosine (8-NH2-Ado) is known to be a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. In this report, to examine whether 8-NH2-Ado had the ability to enhance the radiation-induced cell killing in solid tumor cells, human lung adenocarcinoma A549 cells were irradiated in the presence and absence of 8-NH2-Ado. 8-NH2-Ado significantly increased reproductive cell death and apoptosis in A549 cells exposed to X-rays. When peptide inhibitors against caspase-3, -8, and -9 were utilized to evaluate the involvement of caspases, all inhibitors suppressed the enhancement of radiation-induced apoptosis, suggesting that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated pathways were involved in this enhancement of apoptosis. In addition, in the cells exposed to the treatment combining X-irradiation and 8-NH2-Ado, reduction of the intracellular ATP concentration was essential for survival, and down-regulation of the expression of antiapoptotic proteins such as survivin and XIAP was observed. These results indicate that 8-NH2-Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors.
収録刊行物
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- Journal of Radiation Research
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Journal of Radiation Research 52 (4), 456-463, 2011
Journal of Radiation Research 編集委員会
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詳細情報 詳細情報について
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- CRID
- 1390282680191972736
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- NII論文ID
- 10029122169
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- NII書誌ID
- AA00705792
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- ISSN
- 13499157
- 04493060
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- HANDLE
- 2115/46979
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- NDL書誌ID
- 11164106
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- PubMed
- 21785234
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- NDL
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- 抄録ライセンスフラグ
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