Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300

  title={Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300},
  author={Mauro Rosales and George V. P{\'e}rez and Ailyn C. Ram{\'o}n and Yiliam Cruz and Arielis Rodr{\'i}guez-Ulloa and Vladimir Besada and Yassel Ramos and Dania V{\'a}zquez-Blomquist and Evel{\'i}n Caballero and Daylen Aguilar and Luis Javier Gonz{\'a}lez and Katharina Zettl and Jacek R. Wiśniewski and Yang Ke and Yasser Perera and Silvio E. Perea},
Protein kinase CK2 has emerged as an attractive therapeutic target in acute myeloid leukemia (AML), advent that becomes particularly relevant since the treatment of this hematological neoplasia remains challenging. Here we explored for the first time the effect of the clinical-grade peptide-based CK2 inhibitor CIGB-300 on AML cells proliferation and viability. CIGB-300 internalization and subcellular distribution were also studied, and the role of B23/nucleophosmin 1 (NPM1), a major target for… 

CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model

It is found that NCI-H460 cells are the most CIGB-300-sensitive solid tumor cell line described so far, and the findings provided here uncover novel features linked to CK2 targeting by the CIGb-300 anticancer peptide.

CIGB-300-Regulated Proteome Reveals Common and Tailored Response Patterns of AML Cells to CK2 Inhibition

These findings provide first-hand insights concerning the CIGB-300 antileukemic effect and draw attention to the existence of both common and tailored response patterns triggered by CK2 inhibition in different AML backgrounds, a phenomenon of particular relevance with regard to the pharmacologic blockade of CK2 and personalized medicine.

Gene Expression Profiling Unveils the Temporal Dynamics of CIGB-300-Regulated Transcriptome in AML Cells

Overall, here, for the first time, the temporal dynamics of the gene expression profile regulated by CIGB-300 are explored and fresh molecular clues concerning the antineoplastic effect of CIB-300 in two relevant AML backgrounds are provided.

CIGB-300 Peptide Targets the CK2 Phospho-Acceptor Domain on Human Papillomavirus E7 and Disrupts the Retinoblastoma (RB) Complex in Cervical Cancer Cells

The in vivo physical interaction of the peptide with HPV-16 E7 reduces the CK2-mediated phosphorylation of E7, as well as its binding to the tumour suppressor pRB, unveiling novel molecular clues to the means by which the CIGB-300 triggers cell death in cervical cancer cells.

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

The role of CK2 in gliomagenesis and maintenance seems to have been challenged recently, as some compounds structurally similar to CK2 inhibitors do not inhibit CK2 while still being effective at reducing glioma viability and invasion.

The Immune Regulatory Role of Protein Kinase CK2 and Its Implications for Treatment of Cancer

Parts of CK2 biology, functions of the major innate and adaptive immune cells, and how CK2 regulates the function of immune cells are reviewed to provide perspectives on how CK1 effects in immune cells may impact the treatment of cancers via targeting CK2.

Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection

The findings not only unveil the direct antiviral activity of CIGB-325 on coronavirus infection but also provide molecular clues underlying such effect and reinforce the scientific rationality behind the pharmacologic inhibition of CK2 to treat coronav virus infections.

In vitro Kinase-to-Phosphosite database (iKiP-DB) predicts kinase activity in phosphoproteomic datasets

iKiP-DB can accurately predict changes in kinase activity in published phosphoproteomic datasets for both well-studied and poorly characterized kinases and is widely applicable to facilitate the functional analysis of phosphoSitePlus datasets.

Clinical-Grade Peptide-Based Inhibition of CK2 Blocks Viability and Proliferation of T-ALL Cells and Counteracts IL-7 Stimulation and Stromal Support

The case for anti-CK2 therapeutic intervention in T-ALL is strengthened, demonstrating that CIGB-300 (given its ability to circumvent the effects of pro-leukemic microenvironmental cues) may be a valid tool for clinical intervention in this aggressive malignancy.

Inhibition of protein kinase CK2 with the clinical-grade small ATP-competitive compound CX-4945 or by RNA interference unveils its role in acute myeloid leukemia cell survival, p53-dependent apoptosis and daunorubicin-induced cytotoxicity

Examination of the expression of CK2 in acute myeloid leukemia and its function in cell growth and in the response to the chemotherapeutic agent daunorubicin suggests that CK2 is over expressed across the different acute myEloid leukemia subsets and acts as an important regulator of acute myELoid leukemia cell survival.

Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specifc cell-permeable peptide inhibitor

It is shown that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells, and provides pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL.

CIGB-300: A peptide-based drug that impairs the Protein Kinase CK2-mediated phosphorylation.

The clinical data demonstrate the safety, tolerability, and clinical effects of intratumoral injections of CIGB-300 and provide the foundation for future phase 3 clinical trials in locally advanced cervical cancer in combination with standard chemoradiotherapy.

Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia.

  • Jin Seok KimJ. Eom Y. Min
  • Biology, Chemistry
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2007
Findings strongly suggest protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in AML.

CIGB-300, a novel proapoptotic peptide that impairs the CK2 phosphorylation and exhibits anticancer properties both in vitro and in vivo

These results provide an early proof-of-principle of clinical benefit by using an anti-CK2 approach in cancer and are the first clinical trial where an investigational drug has been used to target the CK2 phosphorylation domain.

Protein Kinase CK2α as an Unfavorable Prognostic Marker and Novel Therapeutic Target in Acute Myeloid Leukemia

The findings strongly suggest protein kinase CK2α as an unfavorable prognostic marker and novel therapeutic target in AML.

Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945

It is evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.

Therapeutic targeting of CK2 in acute and chronic leukemias

Recent advances on the understanding of the signaling pathways involved in CK2 inhibition-mediated effects are summarized with a particular emphasis on the combinatorial use of CK2 inhibitors as novel therapeutic strategies for treating both acute and chronic leukemia patients.

Mechanistic Basis for In Vivo Therapeutic Efficacy of CK2 Inhibitor CX-4945 in Acute Myeloid Leukemia

Evidence is presented that CX-4945, a CK2 inhibitor drug, effectively kills leukemia cells in mouse models and the mechanism of action responsible for these effects is shown, and functional and mechanistic bases are provided for the addition of CK2 inhibitors to AML therapy.