Aminocyanopyridines as anti‐lung cancer agents by inhibiting the STAT3 pathway
| Autor: | Haitang Xu, Sensen Qiu, Xiaoying Huang, Ri Cui, Lingyuan Xu, Liangxing Wang, Xu Liu, Fan Shiqian, Chengguang Zhao, Weitao Fu, Lehe Yang, Liqun Shen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Cancer Research Lung Neoplasms Pyridines Mice Nude Antineoplastic Agents Biology Mice 03 medical and health sciences 0302 clinical medicine Transcription (biology) Cell Line Tumor medicine Animals Humans Phosphorylation Lung cancer STAT3 Molecular Biology Gene Cell Proliferation Mice Inbred BALB C Interleukin-6 Janus Kinase 3 Janus Kinase 2 medicine.disease Xenograft Model Antitumor Assays Molecular Docking Simulation 030104 developmental biology A549 Cells Apoptosis 030220 oncology & carcinogenesis Cancer research STAT protein biology.protein Female Nuclear localization sequence Signal Transduction |
| Zdroj: | Molecular Carcinogenesis. 58:1512-1525 |
| ISSN: | 1098-2744 0899-1987 |
| DOI: | 10.1002/mc.23038 |
| Popis: | Lung cancer is a leading cause of cancer-related death worldwide. Cyanopyridines and aminocyanopyridines with carbon-nitrogen bonds have been proved to exert significant anticancer, antibacterial, and anti-inflammatory effects. In this study, we showed that aminocyanopyridine 3o and 3k displaying potent antitumor activity via inhibiting the signal transducer and activator of transcription 3 (STAT3) pathway. They blocked the constitutive STAT3 phosphorylation in a dose- and time-dependent manner and regulated the transcription of STAT3 target genes encoding apoptosis factors. Most importantly, 3o also inhibited interleukin-6-induced STAT3 activation and nuclear localization. Furthermore, 3o significantly inhibited the tumor growth of H460-derived xenografts. Taken together, these findings suggest that 3o and 3k are promising therapeutic drug candidates for lung cancer by inhibiting persistent STAT3 signaling. |
| Databáze: | OpenAIRE |
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