8-Aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells

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-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-nh 2-ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent.