Disruption of the unfolded protein response (UPR) by lead compound selectively suppresses cancer cell growth
文献类型：期刊论文
| 作者 | Huang, Hejing1,2; Liu, Huanan2; Liu, Changmei2; Fan, Lixia2; Zhang, Xinwen2; Gao, Anhui2; Hu, Xiaobei2; Zhang, Kunzhi2; Cao, Xianchao2; Jiang, Kailong2 |
| 刊名 | CANCER LETTERS
 |
| 出版日期 | 2015-05-01 |
| 卷号 | 360期号:2页码:257-268 |
| 关键词 | Selective cancer therapy Unfolded protein response 2DG UPR disrupter |
| ISSN号 | 0304-3835 |
| DOI | 10.1016/j.canlet.2015.02.029 |
| 文献子类 | Article |
| 英文摘要 | Identifying chemotherapy candidates with high selectivity against cancer cells is a major challenge in cancer treatment. Tumor microenvironments cause chronic endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) as an adaptive response. Here, one novel small-molecule compound, 17#, was discovered as a potent pan-UPR inhibitor. It exhibited good selection for growth inhibition when cancer cells were cultured in 2-deoxy-D-glucose (2DG), mimicking an in vitro glucose-deprived status. Additionally, 17# alone could mildly suppress the growth of HeLa tumor xenografts, and a synergistic anti-cancer effect was observed when 17# was combined with 2DG. A mechanistic study showed that 17#-induced selective anti-cancer effects were highly dependent on UPR inhibition, and overexpressing GRP78 or XBP1s reversed the 17#-induced growth inhibition and cell cycle arrest, partially by delaying the downregulation of the cell cycle regulator cyclin B1. Furthermore, 17# improved the sensitivity of anti-cancer drugs such as doxorubicin or etoposide. Our study presents evidence that disrupting the UPR has selective therapeutic potential and may enhance drug sensitivity. (C) 2015 Elsevier Ireland Ltd. All rights reserved. |
| WOS关键词 | TUMOR MICROENVIRONMENT ; GLUCOSE DEPRIVATION ; 4E-BINDING PROTEIN-1 ; MESSENGER-RNA ; ER STRESS ; INHIBITION ; ACTIVATION ; XBP1 ; 2-DEOXY-D-GLUCOSE ; SURVIVAL |
| 资助项目 | National Natural Science Foundation of China[81473244] ; National Natural Science Foundation of China[81270942] ; National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[81470360] ; National Science and Technology Major Projects for "Major New Drugs Innovation and Development"[2012ZX09301001-004] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000351810600020 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276564]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Yubo |
| 作者单位 | 1.Second Mil Med Univ, Changzheng Hosp, Dept Hematol, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Hejing,Liu, Huanan,Liu, Changmei,et al. Disruption of the unfolded protein response (UPR) by lead compound selectively suppresses cancer cell growth[J]. CANCER LETTERS,2015,360(2):257-268. |
| APA | Huang, Hejing.,Liu, Huanan.,Liu, Changmei.,Fan, Lixia.,Zhang, Xinwen.,...&Li, Jia.(2015).Disruption of the unfolded protein response (UPR) by lead compound selectively suppresses cancer cell growth.CANCER LETTERS,360(2),257-268. |
| MLA | Huang, Hejing,et al."Disruption of the unfolded protein response (UPR) by lead compound selectively suppresses cancer cell growth".CANCER LETTERS 360.2(2015):257-268. |
入库方式： OAI收割
来源：上海药物研究所
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