IC261 suppresses progression of hepatocellular carcinoma in a casein kinase 1 δ/ε independent manner
| Autor: | Jinglin Xia, Peixin Huang, Qian-Wen Rao, Donghe Li, Jialei Sun, Tingting Fang, Zhiying Zhao, Feng Qi, Biwei Yang, Feifei Yuan, Mengzhou Guo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Carcinoma Hepatocellular Indoles Casein Kinase 1 epsilon Biophysics Mice Nude Phloroglucinol Biochemistry 03 medical and health sciences 0302 clinical medicine Pancreatic tumor Cell Line Tumor medicine Animals Humans Fragmentation (cell biology) Molecular Biology Mitosis Protein Kinase Inhibitors Cell Proliferation Mice Inbred BALB C Chemistry Cell growth Liver Neoplasms Cell Biology Cell cycle medicine.disease 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Hepatocellular carcinoma Casein Kinase Idelta Cancer research Disease Progression Casein kinase 1 |
| Zdroj: | Biochemical and biophysical research communications. 523(3) |
| ISSN: | 1090-2104 |
| Popis: | Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide that responds poorly to existing therapies. The Casein kinase 1 (CK1) isoforms CK1δ and CK1e are reported to be highly expressed in several tumor types, and both genetic and pharmacological inhibition of CK1δ/e activity has deleterious effects on tumor cell growth. IC261, an CK1δ/e selectively inhibitor, shows anti-tumor effect against pancreatic tumor and glioblastoma, but its role in HCC remains poorly characterized. In our research, IC261 displayed time- and dose-dependent inhibition of HCC cell proliferation, and induced G2/M arrest and cell apoptosis in vitro. However, the anti-tumor effects of IC261 was independent of CK1δ/e. Additionally, IC261 was verified to induce centrosome fragmentation during mitosis independent of CK1δ status, and intraperitoneal injection of IC261 to HCCLM3 xenograft models inhibited tumor growth. Taken together, our data indicated that IC261 has therapeutic potential for HCC. |
| Databáze: | OpenAIRE |
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