Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region | |
Li, Qiang1,2,4; Zhao, Ting1,2,4; Zheng, Xiaogang1,2,3,4; Li, Ping1,2,4; Jin, Xiaodong1,2,4; Liu, Bingtao1,2,3,4; Sun, Chao2,4; Liu, Xiongxiong1,2,4; Li, Feifei1,2,3,4 | |
刊名 | ONCOTARGET |
2016-05-10 | |
卷号 | 7页码:27267-27279 |
关键词 | Genistein Selective Radiosensitivity Keap1/nrf2 Methylation Oxidative Stress |
ISSN号 | 1949-2553 |
DOI | 10.18632/oncotarget.8403 |
英文摘要 | Non-small cell lung cancer (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo-or radio-resistance. In this study, we showed that genistein selectively exhibited a radiosensitizing effect on NSCLC A549 cells but not on normal lung fibroblast MRC-5 cells. Genistein caused oxidative stress in A549 cells rather than MRC-5 cells, as determined by the oxidation of the ROS-sensitive probe DCFH-DA and oxidative damage marked by MDA, PCO or 8-OHdG content. In A549 instead of MRC-5 cells, genistein reduced the level of methylation in the Keap1 promoter region, leading to an increased mRNA expression, thus effectively inhibited the transcription of Nrf2 to the nucleus, which suppressed the Nrf2-dependent antioxidant and resulted in the upregulation of ROS. Importantly, when combined with radiation, genistein further increased the ROS levels in A549 cells whereas decreasing the radiation-induced oxidative stress in MRC-5 cells, possibly via increasing the expression levels of Nrf2, GSH and HO-1. Moreover, radiation combined with genistein significantly increased cell apoptosis in A549 but not MRC-5 cells. Together, the results herein show that the intrinsic difference in the redox status of A549 and MRC-5 cells could be the target for genistein to selectively sensitize A549 cells to radiation, thereby leading to an increase in radiosensitivity for A549 cells. |
资助项目 | National Natural Science Foundation of China[U1232207] ; National Natural Science Foundation of China[11305223] ; National Natural Science Foundation of China[11505245] ; Chinese Academy of Sciences[Y562020XB0] |
WOS关键词 | Breast-cancer Cells ; Oxidative Stress ; Dna Methylation ; Lung-cancer ; Hepatocellular-carcinoma ; Expression ; Hypermethylation ; 5-azacytidine ; Biomarkers ; Protection |
WOS研究方向 | Oncology ; Cell Biology |
语种 | 英语 |
出版者 | IMPACT JOURNALS LLC |
WOS记录号 | WOS:000377741700027 |
资助机构 | National Natural Science Foundation of China ; Chinese Academy of Sciences |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.186/handle/113462/42877] |
专题 | 近代物理研究所_兰州重离子研究装置 |
作者单位 | 1.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou 730000, Gansu, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China |
推荐引用方式 GB/T 7714 | Li, Qiang,Zhao, Ting,Zheng, Xiaogang,et al. Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region[J]. ONCOTARGET,2016,7:27267-27279. |
APA | Li, Qiang.,Zhao, Ting.,Zheng, Xiaogang.,Li, Ping.,Jin, Xiaodong.,...&Li, Feifei.(2016).Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region.ONCOTARGET,7,27267-27279. |
MLA | Li, Qiang,et al."Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region".ONCOTARGET 7(2016):27267-27279. |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论