title: 8-Aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells.
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-NH(2)-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-NH(2)-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-NH(2)-Ado. 8-NH(2)-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-NH(2)-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-NH(2)-Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors.
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Meike
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamori
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.forename: Masato
authors.initials: M
authors.lastname: Eitaki
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000737:chemistry; D017209:Apoptosis; D061945:Caspase Inhibitors; D016923:Cell Death; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D009101:Multiple Myeloma / Q000188:drug therapy / Q000532:radiotherapy*; D010455:Peptides / Q000037:antagonists & inhibitors; D011419:Propidium / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction; D014965:X-Rays
chemical_list: D061945:Caspase Inhibitors; D010455:Peptides; D011838:Radiation-Sensitizing Agents; D011419:Propidium; C010533:8-aminoadenosine; D000255:Adenosine Triphosphate; D000241:Adenosine