Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 창동신 | - |
dc.date.accessioned | 2018-11-23T16:30:07Z | - |
dc.date.available | 2018-11-23T16:30:07Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.other | OAK-23782 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/247009 | - |
dc.description.abstract | Previously, we identified AMRI-59 as a specific pharmaceutical inhibitor of peroxiredoxin (PRX) I enzyme activity. In this study, we examined whether AMRI-59 acts as a radiosensitizer in non-small cell lung cancer cells using clonogenic assays. The intracellular mechanisms underlying the radiosensitization effect of AMRI-59 were determined via immunoblotting in addition to measurement of ROS generation, mitochondrial potential and cell death. AMRI-59 activity in vivo was examined by co-treating nude mice with the compound and gamma-ionizing radiation (IR), followed by measurement of tumor volumes and apoptosis. The dose enhancement ratios of 30 mu M AMRI-59 in NCI-H460 and NCI-H1299 were 1.51 and 2.12, respectively. Combination of AMRI-59 with IR augmented ROS production and mitochondrial potential disruption via enhancement of PRX I oxidation, leading to increased expression of gamma H2AX, a DNA damage marker, and suppression of ERK phosphorylation, and finally, activation of caspase-3. Notably, inhibition of ROS production prevented ERK suppression, and blockage of ERK in combination with AMRI-59 and IR led to enhanced caspase-3 activation and apoptosis. In a xenograft assay using NCI-H460 and NCI-H1299, combined treatment with AMRI-59 and IR delayed tumor growth by 26.98 and 14.88 days, compared with controls, yielding enhancement factors of 1.73 and 1.37, respectively. Taken together, the results indicate that AMRI-59 functions as a PRX I-targeted radiosensitizer by inducing apoptosis through activation of the ROS/gamma H2AX/caspase pathway and suppression of ERK. | - |
dc.language | English | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.subject | peroxiredoxin | - |
dc.subject | radiosensitizer | - |
dc.subject | AMRI-59 | - |
dc.subject | ROS | - |
dc.subject | non-small cell lung cancer | - |
dc.title | AMRI-59 functions as a radiosensitizer via peroxiredoxin I-targeted ROS accumulation and apoptotic cell death induction | - |
dc.type | Article | - |
dc.relation.issue | 69 | - |
dc.relation.volume | 8 | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 114050 | - |
dc.relation.lastpage | 114064 | - |
dc.relation.journaltitle | ONCOTARGET | - |
dc.identifier.doi | 10.18632/oncotarget.23114 | - |
dc.identifier.wosid | WOS:000419570400058 | - |
dc.identifier.scopusid | 2-s2.0-85039062945 | - |
dc.author.google | Hong, Wan Gi | - |
dc.author.google | Kim, Ju Yeon | - |
dc.author.google | Cho, Jeong Hyun | - |
dc.author.google | Hwang, Sang-Gu | - |
dc.author.google | Song, Jie-Young | - |
dc.author.google | Lee, EunAh | - |
dc.author.google | Chang, Tong-Shin | - |
dc.author.google | Um, Hong-Duck | - |
dc.author.google | Park, Jong Kuk | - |
dc.contributor.scopusid | 창동신(7404726037) | - |
dc.date.modifydate | 20191114141602 | - |