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

  title={CIGB-300, a novel proapoptotic peptide that impairs the CK2 phosphorylation and exhibits anticancer properties both in vitro and in vivo},
  author={Silvio E. Perea and Osvaldo Reyes and Idania Baladr{\'o}n and Yasser Perera and Hern{\'a}n G. Farina and Jeovanis Gil and Arielis Rodr{\'i}guez and Dania Bacard{\'i} and Jos{\'e} Marcelo and Karelia Cosme and Marisol Cruz and Carmen Valenzuela and Pedro Antonio L{\'o}pez-Saura and Yaquel{\'i}n Puchades and Joem M. Serrano and Osmani Mendoza and Lila Castellanos and Aniel S{\'a}nchez and Lazaro Hiram Betancourt and Vladimir Besada and Ricardo Silva and Ernesto L{\'o}pez and Viviana Falcón and Ignacio Hern{\'a}ndez and Margarita Solares and Agueda Santana and Alina D{\'i}az and Thelvia I Ramos and Carlos L{\'o}pez and Juan Manuel Ariosa and Luis Javier Gonz{\'a}lez and Hilda Elisa Garay and Daniel G{\'o}mez and Roberto E. G{\'o}mez and Daniel Fernando Alonso and Hugo Sigman and Luis Herrera and Boris E. Acevedo},
  journal={Molecular and Cellular Biochemistry},
Protein Kinase CK2 is a serine-threonine kinase frequently deregulated in many human tumors. Here, we hypothesized that a peptide binder to the CK2 phosphoacceptor site could exhibit anticancer properties in vitro, in tumor animal models, and in cancer patients. By screening a random cyclic peptide phage display library, we identified the CIGB-300 (formerly P15-Tat), a cyclic peptide which abrogates the CK2 phosphorylation by blocking recombinant substrates in vitro. Interestingly, synthetic… 

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.

Anticancer peptide CIGB-300 binds to nucleophosmin/B23, impairs its CK2-mediated phosphorylation, and leads to apoptosis through its nucleolar disassembly activity

Findings provide important clues by which the CIGB-300 peptide exerts its proapoptotic effect on tumor cells and highlights the suitability of the B23/CK2 pathway for cancer-targeted therapy.

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.

Synergistic interactions of the anti-casein kinase 2 CIGB-300 peptide and chemotherapeutic agents in lung and cervical preclinical cancer models.

Findings provide a rationale for combining the anti-CK2 CIGB-300 peptide with currently available anticancer agents in the clinical setting and indicate platins and taxanes as compounds with major perspectives.

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.

The Combination of the CIGB-300 Anticancer Peptide and Cisplatin Modulates Proteins Related to Cell Survival, DNA Repair and Metastasis in a Lung Cancer Cell Line Model

This is the first report describing the protein array modulated by combining CIGB-300 and cisplatin that will support the rationale for future clinical settings based on a multi-target cancer therapy.

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.

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.

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.



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.

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

This report becomes the first describing the antitumor effect induced by systemic administration of a peptide that targets the acidic phosphorylation domain for CK2 substrates, and reinforces the perspectives of P15‐Tat for the cancer targeted 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.

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 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.

Features and potentials of ATP-site directed CK2 inhibitors.

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.

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.

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.

p53 deficiency and misexpression of protein kinase CK2α collaborate in the development of thymic lymphomas in mice

It is demonstrated that CK2α transgenic mice partially or completely deficient in p53 develop thymic lymphomas at a markedly accelerated rate when compared to p53-deficient mice lacking the transgene.