Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels
文献类型：期刊论文
| 作者 | Li, Na2,4; Wang, Ting2,4; Li, Zongmeng2,4; Ye, Xiaoli2,4; Deng, Bo2,4; Zhuo, Shu2,4; Yao, Pengle2,4; Yang, Mengmei2,4; Mei, Hong2,4; Chen, Xiaofang2,4 |
| 刊名 | CANCER BIOLOGY & MEDICINE
 |
| 出版日期 | 2019 |
| 卷号 | 16期号:2页码:220-+ |
| 关键词 | Dorsomorphin heat shock factor 1 heat shock protein apoptosis cancer |
| ISSN号 | 2095-3941 |
| DOI | 10.20892/j.issn.2095-3941.2018.0235 |
| 文献子类 | Article |
| 英文摘要 | Objective: Heat shock factor 1 (HSF1), a transcriptional regulator of heat shock proteins (HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far. Methods: The mRNA and protein levels of HSF1, HSPs, cleaved PARP, and phosphorylated HSF1 were examined by real-time PCR and Western blot. Forced expression, RNA interference, and immunofluorescence assay were used for mechanistic studies. Cell viability and apoptosis were measured by WST-8 assay and flow cytometry, respectively. Xenograft studies were performed in nude mice to evaluate the effect of dorsomorphin and an HSP90 inhibitor on tumor growth. Results: Dorsomorphin suppressed multiple stimuli-induced and constitutive HSPs expression in cancer cells. Mechanistic studies revealed that dorsomorphin reduced heat-induced HSP expression independent of adenosine monophosphate activated protein kinase. Dorsomorphin reduced heat-stimulated HSF1 Ser320 phosphorylation and nuclear translocation, as well as resting nuclear HSF1 levels in cancer cells. Dorsomorphin induced cancer cell apoptosis by inhibiting HSF1 expression. A structure-activity study revealed that the 4-pyridyl at the 3-site of the pyrazolo [1, 5-a]pyrimidine ring is critical for the anti-HSF1 activities of dorsomorphin. Dorsomorphin sensitized cancer cells to HSP90 and proteasome inhibitors and inhibited HSP70 expression induced by these inhibitors in vitro. In tumor-bearing nude mice, dorsomorphin enhanced HSP90 inhibitor-induced cancer cell apoptosis, tumor growth inhibition, and HSP70 expression. Conclusions: Dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance. Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer. |
| 学科主题 | Oncology ; Research & Experimental Medicine |
| WOS关键词 | TRANSCRIPTION FACTOR HSF1 ; COMPOUND C ; PROTEINS ; BINDING ; HSP70 ; EXPRESSION ; ROLES ; MG132 |
| 语种 | 英语 |
| WOS记录号 | WOS:000469957500003 |
| 出版者 | CHINESE ANTI-CANCER ASSOC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/583]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing 100022, Peoples R China; 2.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai 200031, Peoples R China; 3.Natl Canc Inst Frederick, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA, 4.Shanghai Inst Biol Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Nutr Metab & Food Safety, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Na,Wang, Ting,Li, Zongmeng,et al. Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels[J]. CANCER BIOLOGY & MEDICINE,2019,16(2):220-+. |
| APA | Li, Na.,Wang, Ting.,Li, Zongmeng.,Ye, Xiaoli.,Deng, Bo.,...&,.(2019).Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels.CANCER BIOLOGY & MEDICINE,16(2),220-+. |
| MLA | Li, Na,et al."Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels".CANCER BIOLOGY & MEDICINE 16.2(2019):220-+. |
入库方式： OAI收割
来源：上海营养与健康研究所
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