PMID- 35790285
OWN - NLM
STAT- MEDLINE
DCOM- 20220706
LR  - 20231213
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 42
IP  - 7
DP  - 2022 Jul
TI  - The Casein Kinase 2 Inhibitor CX-4945 Promotes Cholangiocarcinoma Cell Death 
      Through PLK1.
PG  - 3435-3443
LID - 10.21873/anticanres.15830 [doi]
AB  - BACKGROUND/AIM: Casein Kinase 2 (CK2) is a prosurvival protein kinase involved in 
      cell growth/proliferation through the regulation of the cell cycle and apoptosis. 
      CK2 is over-expressed in various cancers, which correlates with a poor prognosis. 
      This study examined the anti-cancer effects of silmitasertib (CX-4945), a CK2 
      inhibitor, on cholangiocarcinoma (CCA) cells. MATERIALS AND METHODS: The effects 
      of CX-4945 on cell viability, cell cycle arrest, and apoptosis in the human 
      cholangiocarcinoma cell lines TFK-1 and SSP-25 were evaluated. Alterations in 
      posttranslational modifications and the levels of cell cycle regulators including 
      p21, Polo-like kinase 1 (PLK1), andp53 were assessed by western blotting. 
      Apoptotic responses were examined using Propidium iodine/Annexin V staining. 
      RESULTS: TFK-1 and SSP-25 cells exposed to CX-4945 showed morphologic changes and 
      a more than 50% decrease in cell viability (p<0.05). Cell cycle arrest at the G2 
      phase was detected following an increase in phosphorylated PLK1 and p21. 
      Furthermore, phospho-PLK1 induced the degradation of p53, which led to the 
      dissociation of Bax from Bcl-xL. The cleavage of Caspase3 and PARP were also 
      induced by CX-4945 treatment. CONCLUSION: CX-4945 induces cell cycle arrest and 
      cell death in cholangiocarcinoma cells via the regulation of PLK1 and p53. This 
      may provide a novel therapeutic strategy for advanced cholangiocarcinoma.
CI  - Copyright (c) 2022 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Lee, DA Sol
AU  - Lee DS
AD  - Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
FAU - Lee, Seonmin
AU  - Lee S
AD  - University of Ulsan Digestive Diseases Research Center, Seoul, Republic of Korea.
FAU - Kim, Chorong
AU  - Kim C
AD  - Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
FAU - Kim, Danbee
AU  - Kim D
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Kim, Kyu-Pyo
AU  - Kim KP
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Yoo, Changhoon
AU  - Yoo C
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea yooc@amc.seoul.kr.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Naphthyridines)
RN  - 0 (Phenazines)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - C6RWP0N0L2 (silmitasertib)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - *Bile Duct Neoplasms/drug therapy
MH  - Bile Ducts, Intrahepatic
MH  - Casein Kinase II
MH  - Cell Cycle Proteins
MH  - Cell Death
MH  - *Cholangiocarcinoma/drug therapy
MH  - Humans
MH  - Naphthyridines
MH  - Phenazines
MH  - Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins
MH  - Tumor Suppressor Protein p53
MH  - Polo-Like Kinase 1
OTO - NOTNLM
OT  - CK2
OT  - CX-4945
OT  - PLK1
OT  - cholangiocarcinoma
EDAT- 2022/07/06 06:00
MHDA- 2022/07/07 06:00
CRDT- 2022/07/05 20:41
PHST- 2022/03/30 00:00 [received]
PHST- 2022/05/24 00:00 [revised]
PHST- 2022/05/25 00:00 [accepted]
PHST- 2022/07/05 20:41 [entrez]
PHST- 2022/07/06 06:00 [pubmed]
PHST- 2022/07/07 06:00 [medline]
AID - 42/7/3435 [pii]
AID - 10.21873/anticanres.15830 [doi]
PST - ppublish
SO  - Anticancer Res. 2022 Jul;42(7):3435-3443. doi: 10.21873/anticanres.15830.