| Autor: |
Maribel Guerra-Vallespi, Julio R Fernández-Massó, Osvaldo Reyes-Acosta, Hilda Garay-Pérez, Isis Torrens-Madrazo, Milaid Granadillo-Rodríguez, Brizaida Oliva-Argüelles, Isbel García, Isabel Guillén-Pérez, Daniel Palenzuela-Gardón, Dania Vázquez-Blomquist, Viviana Falcón-Cama, Osmany Mendoza-Fuentes, Orlando Borras-Hidalgo, Lidia I Novoa-Pérez, Mariela Vázquez-Castillo |
| Jazyk: |
English<br />Spanish; Castilian |
| Předmět: |
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| Zdroj: |
Biotecnología Aplicada, Vol 31, Iss 4, Pp 328-331 |
| Druh dokumentu: |
article |
| ISSN: |
1027-2852 |
| Popis: |
In previous work, we identified the peptide comprising amino acids 32-51 on the antimicrobial protein limulus anti-LPS factor (LALF) from Limulus poliphemus, based on its capacity to bind to the bacterial lipopolysaccharide (LPS). In this study, we designed a chemical peptide library by alanine scanning from the sequence of the LALF32-51 peptide. Four new peptides, named L-2, L-8, L-12 and L-20 by the Ala residue substituted in the given position of the LALF32-51 peptide, were identified as retaining their penetrating activity but also showing antitumor effects when subcutaneously administered in female C57Bl/6 mice after the implantation of malignant TC-1 lung epithelial cells. They significantly increased animal survival (p < 0.05) as compared to LALF32-51. The substitution of Tyr residue to Ala at position 2 in the peptide sequence enhanced the cytotoxic effect, while residues Phe8, Lys12 and Trp20 were essential for the antitumor activity. Moreover, the administration of the L-2 peptide significantly reduced tumor growth in comparison to PBS- or L-20 peptide-treated lung TC-1 cells in C57Bl/6 mice. L-2 was found to deregulate the tumor cell cycle and induces apoptosis, through mechanisms affecting glycolytic and protein biosynthesis pathways. It also significantly increased survival in human colon cancer LS-174T xenotransplanted nude mice for up to 32 days, two of the animals being tumor free. The L-2 peptide could serve as peptide-based prototype drug with potential to reduce tumor load or could be coadministered with conventional chemotherapy. This research granted the 2013 Award of the Cuban National Academy of Sciences. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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