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

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

  • Mol Cell Biochem. 2008 Sep;316(1-2):163-7. doi: 10.1007/s11010-008-9814-5.
Silvio E Perea 1,  Osvaldo Reyes,  Idania Baladron,  Yasser Perera,  Hernán Farina,  Jeovanis Gil,  Arielis Rodriguez,  Dania Bacardi,  Jose L Marcelo,  Karelia Cosme,  Marisol Cruz,  Carmen Valenzuela,  Pedro A López-Saura,  Yaquelin Puchades,  Joem M Serrano,  Osmani Mendoza,  Lila Castellanos,  Aniel Sanchez,  Lazaro Betancourt,  Vladimir Besada,  Ricardo Silva,  Ernesto López,  Viviana Falcón,  Ignacio Hernández,  Margarita Solares,  Agueda Santana,  Alina Díaz,  Thelvia Ramos,  Carlos López,  Juan Ariosa,  Luis J González,  Hilda Garay,  Daniel Gómez,  Roberto Gómez,  Daniel F Alonso,  Hugo Sigman,  Luis Herrera,  Boris Acevedo
Affiliations

Affiliation

  • 1 Center for Genetic Engineering and Biotechnology (CIGB), Havana, 10600, Cuba. silvio.perea@cigb.edu.cu
PMID: 18575815 DOI: 10.1007/s11010-008-9814-5
Abstract

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 led to a dose-dependent antiproliferative effect in a variety of tumor cell lines and induced Apoptosis as evidenced by rapid Caspase activation. Importantly, CIGB-300 elicited significant antitumor effect both by local and systemic administration in murine syngenic tumors and human tumors xenografted in nude mice. Finally, we performed a First-in-Man trial with CIGB 300 in patients with cervical malignancies. The peptide was found to be safe and well tolerated in the dose range studied. Likewise, signs of clinical benefit were clearly identified after the CIGB-300 treatment as evidenced by significant decrease of the tumor lesion area and histological examination. Our results provide an early proof-of-principle of clinical benefit by using an anti-CK2 approach in Cancer. Furthermore, this is the first clinical trial where an investigational drug has been used to target the CK2 phosphorylation domain.

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