Protein kinase CK2 promotes cancer cell viability via up-regulation of cyclooxygenase-2 expression and enhanced prostaglandin E2 production

2011 ◽  
Vol 112 (11) ◽  
pp. 3167-3175 ◽  
Author(s):  
Roger Yefi ◽  
Daniela P. Ponce ◽  
Ignacio Niechi ◽  
Eduardo Silva ◽  
Pablo Cabello ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Prostaglandin E2 ◽  
Cell Viability ◽  
Cancer Cell ◽  
Protein Kinase Ck2 ◽  
Cyclooxygenase 2 ◽  
Kinase Ck2

scholarly journals Targeting protein kinase CK2 suppresses bladder cancer cell survival via the glucose metabolic pathway

Oncotarget ◽  
2016 ◽  
Vol 7 (52) ◽  
pp. 87361-87372 ◽  
Author(s):  
Xiaolei Zhang ◽  
Xiao Yang ◽  
Chengdi Yang ◽  
Peng Li ◽  
Wenbo Yuan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Kinase ◽  
Cell Survival ◽  
Cancer Cell ◽  
Metabolic Pathway ◽  
Protein Kinase Ck2 ◽  
Bladder Cancer Cell ◽  
Cancer Cell Survival ◽  
Kinase Ck2

scholarly journals In Vitro and in Silico Evaluation of Bikaverin as a Potent Inhibitor of Human Protein Kinase CK2

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1380 ◽  
Author(s):  
Samer Haidar ◽  
Dagmar Aichele ◽  
Robin Birus ◽  
Janine Hielscher ◽  
Tuomo Laitinen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cell Viability ◽  
Binding Site ◽  
Protein Kinase Ck2 ◽  
Potent Inhibitor ◽  
Cell Permeability ◽  
Atp Binding Site ◽  
Kinase Ck2

Protein kinase CK2 is an emerging target for therapeutic intervention in human diseases, particularly in cancer. Inhibitors of this enzyme are currently in clinical trials, indicating the druggability of human CK2. By virtual screening of the ZINC database, we found that the natural compound bikaverin can fit well in the ATP binding site of the target enzyme CK2. By further in vitro evaluation using CK2 holoenzyme, bikaverin turned to be a potent inhibitor with an IC50 value of 1.24 µM. In this work, the cell permeability of bikaverin was determined using a Caco-2 cell permeability assay as a prerequisite for cellular evaluation and the compound turned out to be cell permeable with a Papp- value of 4.46 × 10−6 cm/s. Bikaverin was tested for its effect on cell viability using a MTT assay and cell proliferation using an EdU assay in different cancer cell lines (MCF7, A427 and A431 cells). Cell viability and cell proliferation were reduced dramatically after treatment with 10 µM bikaverin for 24 h. Additionally the IncuCyte® live-cell imaging system was applied for monitoring the cytotoxicity of bikaverin in the three tested cancer cell lines. Finally, molecular dynamic studies were performed to clarify the ligand binding mode of bikaverin at the ATP binding site of CK2 and to identify the amino acids involved.

Protein kinase CK2 regulates prostate cancer cell migration and proliferation through phosphorylation of PRH/HHEX

2016 ◽  
Vol 61 ◽  
pp. S97
Author(s):  
E. Marcolino de Assis ◽  
Y. Hasan Siddiqui ◽  
R.M. Kershaw ◽  
E.H. Humphreys ◽  
S. Chaudhri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Protein Kinase ◽  
Cancer Cell ◽  
Protein Kinase Ck2 ◽  
Prostate Cancer Cell ◽  
Cancer Cell Migration ◽  
Cell Migration And Proliferation ◽  
Kinase Ck2

Protein kinase CK2 regulates AKT, NF-κB and STAT3 activation, stem cell viability and proliferation in acute myeloid leukemia

Leukemia ◽  
2016 ◽  
Vol 31 (2) ◽  
pp. 292-300 ◽  
Author(s):  
L Quotti Tubi ◽  
S Canovas Nunes ◽  
A Brancalion ◽  
E Doriguzzi Breatta ◽  
S Manni ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Protein Kinase ◽  
Cell Viability ◽  
Myeloid Leukemia ◽  
Protein Kinase Ck2 ◽  
Kinase Ck2 ◽  
Acute Myeloid

scholarly journals CX-4945 Induces Methuosis in Cholangiocarcinoma Cell Lines by a CK2-Independent Mechanism

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 283 ◽  
Author(s):  
Jomnarong Lertsuwan ◽  
Kornkamon Lertsuwan ◽  
Anyaporn Sawasdichai ◽  
Nathapol Tasnawijitwong ◽  
Ka Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Protein Kinase Ck2 ◽  
Extracellular Fluid ◽  
Multiple Cancer ◽  
Cholangiocarcinoma Cell ◽  
Kinase Ck2

Cholangiocarcinoma is a disease with a poor prognosis and increasing incidence and hence there is a pressing unmet clinical need for new adjuvant treatments. Protein kinase CK2 (previously casein kinase II) is a ubiquitously expressed protein kinase that is up-regulated in multiple cancer cell types. The inhibition of CK2 activity using CX-4945 (Silmitasertib) has been proposed as a novel treatment in multiple disease settings including cholangiocarcinoma. Here, we show that CX-4945 inhibited the proliferation of cholangiocarcinoma cell lines in vitro. Moreover, CX-4945 treatment induced the formation of cytosolic vacuoles in cholangiocarcinoma cell lines and other cancer cell lines. The vacuoles contained extracellular fluid and had neutral pH, features characteristic of methuosis. In contrast, simultaneous knockdown of both the α and α′ catalytic subunits of protein kinase CK2 using small interfering RNA (siRNA) had little or no effect on the proliferation of cholangiocarcinoma cell lines and failed to induce the vacuole formation. Surprisingly, low doses of CX-4945 increased the invasive properties of cholangiocarcinoma cells due to an upregulation of matrix metallopeptidase 7 (MMP-7), while the knockdown of CK2 inhibited cell invasion. Our data suggest that CX-4945 inhibits cell proliferation and induces cell death via CK2-independent pathways. Moreover, the increase in cell invasion brought about by CX-4945 treatment suggests that this drug might increase tumor invasion in clinical settings.

scholarly journals 5,6-diiodo-1H-benzotriazole: new TBBt analogue that minutely affects mitochondrial activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Paprocki ◽  
Maria Winiewska-Szajewska ◽  
Elżbieta Speina ◽  
Róża Kucharczyk ◽  
Jarosław Poznański
Keyword(s):  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Protein Kinase Ck2 ◽  
Cancer Cell Lines ◽  
Competitive Inhibitor ◽  
Attractive Alternative ◽  
Mitochondrial Activity ◽  
Mitochondrial Inner Membrane ◽  
Kinase Ck2

Abstract4,5,6,7-Tetrabromo-1H-benzotriazole is widely used as the reference ATP-competitive inhibitor of protein kinase CK2. Herein, we study its new analogs: 5,6-diiodo- and 5,6-diiodo-4,7-dibromo-1H-benzotriazole. We used biophysical (MST, ITC) and biochemical (enzymatic assay) methods to describe the interactions of halogenated benzotriazoles with the catalytic subunit of human protein kinase CK2 (hCK2α). To trace the biological activity, we measured their cytotoxicity against four reference cancer cell lines and the effect on the mitochondrial inner membrane potential. The results obtained lead to the conclusion that iodinated compounds are an attractive alternative to brominated ones. One of them retains the cytotoxicity against selected cancer cell lines of the reference TBBt with a smaller side effect on mitochondrial activity. Both iodinated compounds are candidate leaders in the further development of CK2 inhibitors.

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