title: Antitumor efficacy, pharmacokinetic and biodistribution studies of the anticancer peptide CIGB-552 in mouse models.
abstract: Accumulation of the COMMD1 protein as a druggable pharmacology event to target cancer cells has not been evaluated so far in cancer animal models. We have previously demonstrated that a second-generation peptide, with cell-penetrating capacity, termed CIGB-552, was able to induce apoptosis mediated by stabilization of COMMD1. Here, we explore the antitumor effect by subcutaneous administration of CIGB-552 in a therapeutic schedule. Outstandingly, a significant delay of tumor growth was observed at 0.2 and 0.7 mg/kg (p < 0.01) or 1.4 mg/kg (p < 0.001) after CIGB-552 administration in both syngeneic murine tumors and patient-derived xenograft models. Furthermore, we evidenced that (131)I-CIGB-552 peptide was actually accumulated in the tumors after administration by subcutaneous route. A typical serine-proteases degradation pattern for CIGB-552 in BALB/c mice serum was identified. Further, biological characterization of the main metabolites of the peptide CIGB-552 suggests that the cell-penetrating capacity plays an important role in the cytotoxic activity. This report is the first in describing the antitumor effect induced by systemic administration of a peptide that targets COMMD1 for stabilization. Moreover, our data reinforce the perspectives of CIGB-552 for cancer targeted therapy.
authors.affiliation: Pharmaceutical Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, 10600, Cuba.
authors.forename: Maribel G
authors.initials: MG
authors.lastname: Vallespí
authors.forename: Gilmara
authors.initials: G
authors.lastname: Pimentel
authors.forename: Ania
authors.initials: A
authors.lastname: Cabrales-Rico
authors.forename: Julio
authors.initials: J
authors.lastname: Garza
authors.forename: Brizaida
authors.initials: B
authors.lastname: Oliva
authors.forename: Osmani
authors.initials: O
authors.lastname: Mendoza
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Gomez
authors.forename: Tais
authors.initials: T
authors.lastname: Basaco
authors.forename: Iraida
authors.initials: I
authors.lastname: Sánchez
authors.forename: Carlos
authors.initials: C
authors.lastname: Calderón
authors.forename: Juan C
authors.initials: JC
authors.lastname: Rodriguez
authors.forename: Maria Rivera
authors.initials: MR
authors.lastname: Markelova
authors.forename: Iduna
authors.initials: I
authors.lastname: Fichtner
authors.forename: Soledad
authors.initials: S
authors.lastname: Astrada
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollati-Fogolín
authors.forename: Hilda E
authors.initials: HE
authors.lastname: Garay
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Reyes
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D060829:Arthropod Proteins / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D055550:Protein Stability / Q000187:drug effects; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D060829:Arthropod Proteins; C000598873:CIGB-552 peptide; C480519:COMMD1 protein, human; D057846:Cell-Penetrating Peptides; C034705:antilipopolysaccharide factor (Limulus)
keywords: COMMD1; cancer animal models; cancer targeted therapy; cytotoxic peptide; pharmacokinetic