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

Feifei Yuan; Donghe Li; Mengzhou Guo; Tingting Fang; Jialei Sun; Feng Qi; Qianwen Rao; Zhiying Zhao; Peixin Huang; Biwei Yang; Jinglin Xia

doi:10.1016/j.bbrc.2019.12.105

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. Epub 2020 Jan 15.

Authors

Feifei Yuan¹, Donghe Li², Mengzhou Guo¹, Tingting Fang¹, Jialei Sun¹, Feng Qi¹, Qianwen Rao³, Zhiying Zhao¹, Peixin Huang¹, Biwei Yang⁴, Jinglin Xia⁵

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: yang.biwei@zs-hospital.sh.cn.
⁵ Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China. Electronic address: xiajinglin@fudan.edu.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / metabolism
Casein Kinase 1 epsilon / antagonists & inhibitors*
Casein Kinase 1 epsilon / metabolism
Casein Kinase Idelta / antagonists & inhibitors*
Casein Kinase Idelta / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Disease Progression
Humans
Indoles / pharmacology
Indoles / therapeutic use*
Liver Neoplasms / drug therapy*
Liver Neoplasms / metabolism
Male
Mice, Inbred BALB C
Mice, Nude
Phloroglucinol / analogs & derivatives*
Phloroglucinol / pharmacology
Phloroglucinol / therapeutic use
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use*

Substances

IC 261
Indoles
Protein Kinase Inhibitors
Phloroglucinol
Casein Kinase 1 epsilon
Casein Kinase Idelta