1. 2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile, Exerts Anti-bladder Activities through IGF-1R/STAT3 Signaling
- Author
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He Lin, Chai Baoshan, Wang Wanqiu, Wang Yunhua, Bi Yi, Guang Haihong, Jiao Jiayuan, Ran Zhaojin, and Bu Yanxin
- Subjects
STAT3 Transcription Factor ,MAPK/ERK pathway ,Cell Survival ,medicine.medical_treatment ,Urinary Bladder ,Antineoplastic Agents ,Apoptosis ,010402 general chemistry ,01 natural sciences ,Cell Line ,Receptor, IGF Type 1 ,Cell Line, Tumor ,Nitriles ,Drug Discovery ,medicine ,Humans ,Cytotoxic T cell ,Cytotoxicity ,010405 organic chemistry ,Chemistry ,Kinase ,Growth factor ,Cell Cycle ,Receptors, Somatomedin ,General Chemistry ,General Medicine ,Cell cycle ,Molecular biology ,0104 chemical sciences ,Molecular Docking Simulation ,Urinary Bladder Neoplasms ,STAT protein ,Signal Transduction - Abstract
2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile (SYD007) is a small molecule compound that was synthesized according to the structure of diarylamine. In this study, we evaluated the anti-bladder activities of SYD007, and determined its cytotoxic mechanism. We found that SYD007 exerted cytotoxicity to bladder cancer cells. Furthermore, SYD007 induced bladder cancer cell early apoptosis and arrested cell cycle. Mechanistically, SYD007 suppressed phosphorylated signal transducer and activator of transcription 3 (p-STAT3) (Tyr705) level in parallel with increases of p-extracellular signal-regulated kinase (ERK) and p-AKT. SYD007 significantly inhibited insulin-like growth factor 1 (IGF-1)-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in SYD007-treated cells, suggesting that SYD007 acted primarily at a posttranscriptional level. Using molecular docking analysis, SYD007 was identified as an IGF-1R inhibitor. In summary, we reported that SYD007 exerted anti-bladder activities, and these effects were partially due to inhibition of IGF-1R/STAT3 signaling.
- Published
- 2019