ER stress signaling in ARPE-19 cells after inhibition of protein kinase CK2 by CX-4945

Intemann, Johanna; Saidu, Nathaniel Edward Bennett; Schwind, Lisa; Montenarh, Mathias

doi:10.1016/j.cellsig.2014.03.014

Cited by 29 publications

(25 citation statements)

References 31 publications

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“…However, its presence appears to be necessary for the early phase or the initiation of differentiation. It is tempting to speculate that CK2 is dispensable in the adult organism and in terminally differentiated cells, as inhibition of CK2 activity is not detrimental for the survival of normal cells (94). However, with high probability, cells of the stem cell niche, which are also present in different tissues and organs of the adult organism, have to be excluded from this statement.…”

Section: Resultsmentioning

confidence: 99%

Protein kinase CK2 in development and differentiation

Götz

Montenarh

2016

Biomedical Reports

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Among the human kinomes, protein kinase CK2 (formerly termed casein kinase II) is considered to be essential, as it is implicated in the regulation of various cellular processes. Experiments with pharmacological inhibitors of the kinase activity of CK2 provide evidence that CK2 is essential for development and differentiation. Therefore, the present review addresses the role of CK2 during embryogenesis, neuronal, adipogenic, osteogenic and myogenic differentiation in established model cell lines, and in embryonic, neural and mesenchymal stem cells. CK2 kinase activity appears to be essential in the early stages of differentiation, as CK2 inhibition at early time points generally prevents differentiation. In addition, the present review reports on target proteins of CK2 in embryogenesis and differentiation.

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Section: Resultsmentioning

confidence: 99%

Protein kinase CK2 in development and differentiation

Götz

Montenarh

2016

Biomedical Reports

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“…This is associated with a reduced leukocyte adhesion to endothelial cells under TNF-α-induced inflammatory conditions. During the last years, several studies reported that inhibition of CK2 selectively induces apoptosis in tumor cells relative to normal cells [37]. Accordingly, CK2 has been suggested as a potential therapeutic target for the development of novel cancer drugs [38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of protein kinase CK2 suppresses tumor necrosis factor (TNF)-α-induced leukocyte–endothelial cell interaction

Ampofo

Rudzitis‐Auth

Dahmke

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Inflammatory endothelial processes are regulated by the nuclear factor-κB (NF-κB) pathway, which involves phosphorylation of p65. Because p65 is a substrate of CK2, we herein investigated, whether this pleiotropic protein kinase may be a beneficial anti-inflammatory target. For this purpose, we analyzed in human dermal microvascular endothelial cells (HDMEC) the effect of CK2 inhibition by quinalizarin and CX-4945 on cell viability, adhesion molecule expression and NF-κB pathway activation. Leukocyte binding to HDMEC was assessed in an in vitro adhesion assay. Dorsal skinfold chambers in BALB/c mice were used to study leukocyte-endothelial cell interaction and leukocyte transmigration by means of repetitive intravital fluorescence microscopy and immunohistochemistry. We found that quinalizarin and CX-4945 effectively suppressed the activity of CK2 in HDMEC without affecting their viability. This was associated with a significant down-regulation of tumor necrosis factor (TNF)-α-induced E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression due to a reduction of shuttling, phosphorylation and transcriptional activity of the NF-κB complex. In consequence, leukocyte binding to quinalizarin- and CX-4945-treated HDMEC was diminished. Finally, CX-4945 treatment significantly decreased the numbers of adherent and transmigrated leukocytes in dorsal skinfold chambers exposed to TNF-α in vivo. These findings indicate that CK2 is a key regulator of leukocyte-endothelial cell interaction in inflammation by regulating the expression of E-selectin, ICAM-1 and VCAM-1 via affecting the transcriptional activity of the NF-κB complex. Accordingly, CK2 represents a promising target for the development of novel anti-inflammatory drugs.

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“…CX-4945 reportedly modulates not only CK2 activity, but also PI3K-Akt-mTOR signaling, the Notch pathway, the PI3K-Akt-mTOR pathway, the focal adhesion kinase-Src-paxillin signaling cascade, ER stress signaling, NF-κB, and Bcl-xL, ERK, AP-1, and IL-8 gene activities (37)(38)(39)(40)(41)(42). The pleotropic effect of CX-4945 and off-target effects of CK2 might potentially affect the inhibition of osteosarcoma growth.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of casein kinase 2 prevents growth of human osteosarcoma

et al. 2016

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High-dose chemotherapy and surgical treatment have improved the prognosis of osteosarcoma. However, more than 20% of patients with osteosarcoma still have a poor prognosis. We investigated the expression and function of casein kinase 2 (CK2) in osteosarcoma growth. We then examined the effects of CX-4945, a CK2 inhibitor, on osteosarcoma growth in vitro and in vivo to apply our findings to the clinical setting. We examined the expression of CK2α and CK2β by western blot analysis, and performed WST-1 assays using CK2α and CK2β siRNA or CX-4945. Flow cytometry and western blot analyses were performed to evaluate apoptotic cell death. Xenograft models were used to examine the effect of CX-4945 in vivo. Western blot analysis revealed upregulation of CK2α and CK2β in human osteosarcoma cell lines compared with human osteoblast cells or mesenchymal stem cells. WST assay showed that knockdown of CK2α or CK2β by siRNA inhibited the proliferation of human osteosarcoma cells. Treatment with 3 µM of CX-4945 inhibited osteosarcoma cell proliferation; however, the same concentration of CX-4945 did not affect the proliferation of human mesenchymal stem cells. Additionally, treatment with CX-4945 inhibited the proliferation of human osteosarcoma cells in a dose-dependent manner. Western blot and flow cytometry analyses showed that treatment with CX-4945 promoted apoptotic death of osteosarcoma cells. The xenograft model showed that treatment with CX-4945 significantly prevented osteosarcoma growth in vivo compared with control vehicle treatment. Our findings indicate that CK2 may be an attractive therapeutic target for treating osteosarcoma.

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ER stress signaling in ARPE-19 cells after inhibition of protein kinase CK2 by CX-4945

Cited by 29 publications

References 31 publications

Protein kinase CK2 in development and differentiation

Protein kinase CK2 in development and differentiation

Inhibition of protein kinase CK2 suppresses tumor necrosis factor (TNF)-α-induced leukocyte–endothelial cell interaction

Inhibition of casein kinase 2 prevents growth of human osteosarcoma

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