Systemic administration of a peptide that impairs the protein kinase (CK2) phosphorylation reduces solid tumor growth in mice

  title={Systemic administration of a peptide that impairs the protein kinase (CK2) phosphorylation reduces solid tumor growth in mice},
  author={Yasser Perera and Hern{\'a}n G. Farina and Ignacio Hern{\'a}ndez and Osmany Mendoza and Joem M. Serrano and Osvaldo Reyes and Daniel Eduardo Gomez and Roberto E. G{\'o}mez and Boris E. Acevedo and Daniel Fernando Alonso and Silvio E. Perea},
  journal={International Journal of Cancer},
The antitumor efficacy of the CK2 inhibitors so far described has not been extensively evaluated in cancer animal models. We have previously demonstrated that a proapoptotic cyclic peptide termed P15 delivered into the cells by the Tat Cell Penetrating Peptide was able to abrogate the CK2‐mediated phosphorylation and induce tumor regression when injected directly into solid tumors in mice. Here we explored the antitumor effect by systemic administration of P15‐Tat in a consecutive 5‐day… 

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.

CIGB-300, a proapoptotic peptide, inhibits angiogenesis in vitro and in vivo.

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

The results not only provide cellular and molecular insights unveiling the complexity of the CIGB-300 anti-leukemic effect in AML cells, but also reinforce the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.

Systemic administration of antisense oligonucleotides simultaneously targeting CK2α and α′ subunits reduces orthotopic xenograft prostate tumors in mice

It is proposed that the molecular downregulation of CK2 through bispecific targeting of the two catalytic subunits may be uniquely useful for therapeutic elimination of tumors.

Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization

Encouraging results suggest that CIGB-300 could be used for the management of breast cancer as an adjuvant therapy after surgery, limiting tumor metastatic spread and thus protecting the patient from distant recurrence.

Sensitivity of tumor cells towards CIGB‐300 anticancer peptide relies on its nucleolar localization

This work evidenced that CIGB‐300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target, and suggests that further improvements to this cell penetrating peptide‐based drug should entail its more efficient intracellular delivery at such sub cellular localization.

Targeting CK2 for Cancer Therapy Using a Nanomedicine Approach

Protected and malignant cell-specific delivery of a therapeutic is a promising target-specific and versatile approach for cancer therapy, and both the TBG encapsulation technology and the anti-CK2 oligonucleotide approach demonstrate substantial potential for the treatment of malignancy.

A casein kinase 2 inhibitor is a potent anti-cancer drug candidate

In vitro DMAT induces significant proliferation arrest and apoptosis at a similar level in all the cancer cell lines tested, and an in vivo pilot toxicity study showed that DMAT is not toxic to mice.

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.



Antitumor Effect of a Novel Proapoptotic Peptide that Impairs the Phosphorylation by the Protein Kinase 2 (Casein Kinase 2)

A new proapoptotic cyclic peptide is identified that blocks the CK2 phosphorylation and exhibits antitumor effect in vivo, indicating that the P15 peptide may potentially be used clinically to treat solid tumors or as an adjuvant for cancer therapy.

Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model.

This is the first report to provide important new evidence as an initial "proof of principle" for the potential application of antisense CK2alpha in cancer therapy, paving the way for future detailed studies of approaches to targeting CK2 in vivo to induce cancer cell death.

Targeting CK2 for cancer therapy.

It is shown that antisense CK2alpha is particularly potent in inducing apoptosis in cancer cells in culture as well as in xenograft models of cancer such as prostate cancer and squamous cell carcinoma of head and neck.

Preclinical Evaluation of the Breast Cancer Cell-Binding Peptide, p160

Purpose: Selective delivery of drugs into the target tissue is expected to result in high drug concentrations in the tissue of interest and therefore enhanced drug efficacy. To develop a

Multiple myeloma cell survival relies on high activity of protein kinase CK2.

Analysis of MM cell lines and highly purified malignant plasma cells in patients with MM revealed higher protein and CK2 activity levels than in controls, suggesting that it might play a crucial role in controlling survival and sensitivity to chemotherapeutics of malignant Plasma cells.

Protein kinase CK2: Signaling and tumorigenesis in the mammary gland

CK2 may promote breast cancer through dysregulation of key pathways of transcriptional control in the mammary epithelium, and inhibition of CK2 has a potential role in the treatment of breast and other cancers.

Protein kinase CK2 signal in neoplasia.

Of considerable interest is the possibility that CK2 dysregulation in tumors may influence the apoptotic activity in those cells, and approaches to interfering with the CK2 signal may provide a useful means for inducing tumor cell death.

A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity

The results suggested that r7-kla is an apoptosis inducer and can be potentially used as an antitumor agent, especially when combined with the appropriate systemic delivery systems.

One‐thousand‐and‐one substrates of protein kinase CK2?

  • F. MeggioL. Pinna
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2003
An analysis of 308 sites phosphorylated by CK2 highlights the paramount relevance of negatively charged side chains that are (by far) predominant over any other residues at positions n+3 (the most crucial one), n+1, and n+2.

Protein kinase CK2 and its role in cellular proliferation, development and pathology

The structure of the catalytic subunit with the fixed positioning of the activation segment in the active conformation through its own aminoterminal region suggests a regulation at the transcriptional level making a regulation by second messengers unlikely.