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

@article{Perea2008CIGB300AN,
  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},
  year={2008},
  volume={316},
  pages={163-167}
}
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… Expand
CIGB-300, a proapoptotic peptide, inhibits angiogenesis in vitro and in vivo.
TLDR
The CIGB-300 was tested in vivo on chicken embryo chorioallantoic membranes (CAM), and a large number of newly formed blood vessels were significantly regressed, suggesting that CIGb-300 has a potential as an antiangiogenic treatment. Expand
CIGB-300: A peptide-based drug that impairs the Protein Kinase CK2-mediated phosphorylation.
TLDR
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. Expand
Anticancer peptide CIGB-300 binds to nucleophosmin/B23, impairs its CK2-mediated phosphorylation, and leads to apoptosis through its nucleolar disassembly activity
TLDR
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. Expand
Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization
TLDR
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. Expand
Synergistic interactions of the anti-casein kinase 2 CIGB-300 peptide and chemotherapeutic agents in lung and cervical preclinical cancer models.
TLDR
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. Expand
Sensitivity of tumor cells towards CIGB‐300 anticancer peptide relies on its nucleolar localization
TLDR
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. Expand
Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300
TLDR
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. Expand
Mechanisms of cellular uptake, intracellular transportation, and degradation of CIGB-300, a Tat-conjugated peptide, in tumor cell lines.
TLDR
This work studied differential antiproliferative behavior in terms of cellular uptake, intracellular transportation, and degradation in tumor cell lines with dissimilar sensitivity to CIGB-300 to suggest a mechanism of internalization, vesicular transportation, but also suggests degradation in highly sensitive cells. Expand
Clinical-Grade Peptide-Based Inhibition of CK2 Blocks Viability and Proliferation of T-ALL Cells and Counteracts IL-7 Stimulation and Stromal Support
TLDR
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. Expand
Therapeutic targeting of CK2 in acute and chronic leukemias
TLDR
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. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 19 REFERENCES
Antitumor Effect of a Novel Proapoptotic Peptide that Impairs the Phosphorylation by the Protein Kinase 2 (Casein Kinase 2)
TLDR
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. Expand
Systemic administration of a peptide that impairs the protein kinase (CK2) phosphorylation reduces solid tumor growth in mice
TLDR
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. Expand
Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model.
TLDR
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. Expand
Multiple myeloma cell survival relies on high activity of protein kinase CK2.
TLDR
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. Expand
Protein kinase CK2 signal in neoplasia.
TLDR
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. Expand
Features and potentials of ATP-site directed CK2 inhibitors.
TLDR
The remarkable pro-apoptotic efficacy of these compounds toward cell lines derived from a wide spectrum of tumors, disclose the possibility that in perspective CK2 inhibitors might become leads for the development of anti-cancer drugs. Expand
Protein kinase CK2 and its role in cellular proliferation, development and pathology
TLDR
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. Expand
Protein kinase CK2: Signaling and tumorigenesis in the mammary gland
TLDR
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. Expand
One‐thousand‐and‐one substrates of protein kinase CK2?
  • F. Meggio, L. Pinna
  • Biology, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2003
TLDR
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. Expand
p53 deficiency and misexpression of protein kinase CK2α collaborate in the development of thymic lymphomas in mice
TLDR
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. Expand
...
1
2
...