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8-Aminoadenosine Enhances Radiation-induced Cell Death in Human Lung Carcinoma A549 Cells

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Title: 8-Aminoadenosine Enhances Radiation-induced Cell Death in Human Lung Carcinoma A549 Cells
Authors: MEIKE, Shunsuke Browse this author
YAMAMORI, Tohru Browse this author
YASUI, Hironobu Browse this author
EITAKI, Masato Browse this author
MATSUDA, Akira Browse this author →KAKEN DB
INANAMI, Osamu Browse this author →KAKEN DB
Keywords: Radiosensitization
8-Aminoadenosine (8-NH2-Ado)
Apoptosis
Issue Date: 2011
Journal Title: Journal of Radiation Research
Volume: 52
Issue: 4
Start Page: 456
End Page: 463
Publisher DOI: 10.1269/jrr.10188
PMID: 21785234
Abstract: 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.
Description: JOI: JST.JSTAGE/jrr/10188
Type: article
URI: http://hdl.handle.net/2115/46979
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 稲波 修

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