title: Systemic administration of a peptide that impairs the protein kinase (CK2) phosphorylation reduces solid tumor growth in mice.
abstract: 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 schedule through either intraperitoneal or intravenous route. Importantly, significant delay of tumor growth was observed at 2 mg/kg (p < 0.05), 10 mg/kg (p < 0.01) or 40 mg/kg (p < 0.001) after P15-Tat administration both in syngeneic murine tumors and human tumors xenografted in nude mice. In line with this, the systemic administration of P15-Tat induced apoptosis in the tumor as evidenced by in situ DNA fragmentation. Furthermore, we evidenced that 99mTc-labeled P15-Tat peptide was certainly accumulated on the tumors after administration by both routes. 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. Also, our data reinforces the perspectives of P15-Tat for the cancer targeted therapy.
authors.affiliation: Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Perera
authors.forename: Hernán G
authors.initials: HG
authors.lastname: Farina
authors.forename: Ignacio
authors.initials: I
authors.lastname: Hernández
authors.forename: Osmany
authors.initials: O
authors.lastname: Mendoza
authors.forename: Joem M
authors.initials: JM
authors.lastname: Serrano
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Reyes
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Gómez
authors.forename: Roberto E
authors.initials: RE
authors.lastname: Gómez
authors.forename: Boris E
authors.initials: BE
authors.lastname: Acevedo
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Alonso
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Perea
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000473:pathology*; D047390:Casein Kinase II / Q000378:metabolism*; D045744:Cell Line, Tumor; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000494:pharmacology*; D005260:Female; D015696:Gene Products, tat / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D015696:Gene Products, tat; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II