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Aminocyanopyridines as antiālung cancer agents by inhibiting the STAT3 pathway
- Source :
- Molecular Carcinogenesis. 58:1512-1525
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 10982744 and 08991987
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Molecular Carcinogenesis
- Accession number :
- edsair.doi.dedup.....0e6b85eeb951c18cc7264c919addffe2