2. Academic Validation
  3. IC261 suppresses progression of hepatocellular carcinoma in a casein kinase 1 δ/ε independent manner

IC261 suppresses progression of hepatocellular carcinoma in a casein kinase 1 δ/ε independent manner

  • Biochem Biophys Res Commun. 2020 Mar 12;523(3):809-815. doi: 10.1016/j.bbrc.2019.12.105.
Feifei Yuan 1,  Donghe Li 2,  Mengzhou Guo 1,  Tingting Fang 1,  Jialei Sun 1,  Feng Qi 1,  Qianwen Rao 3,  Zhiying Zhao 1,  Peixin Huang 1,  Biwei Yang 4,  Jinglin Xia 5
Affiliations

Affiliations

  • 1 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
  • 2 State Key Laboratory for Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China; School of Life Sciences and Biotechnology and School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
  • 3 Minhang Hospital, Shanghai Medical School of Fudan University, Shanghai, 201100, PR China.
  • 4 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China. Electronic address: [email protected].
  • 5 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China. Electronic address: [email protected].
PMID: 31954519 DOI: 10.1016/j.bbrc.2019.12.105
Abstract

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 CK1ε are reported to be highly expressed in several tumor types, and both genetic and pharmacological inhibition of CK1δ/ε activity has deleterious effects on tumor cell growth. IC261, an CK1δ/ε 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/ε. 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.

Keywords

Casein kinase 1 δ/ε; Cell cycle; Centrosome fragmentation; Hepatocellular carcinoma; IC261.

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