Guerra-Vallespi M, Fernández-Massó JR, Reyes-Acosta O, Garay-Pérez H, Torrens-Madrazo I, Granadillo-Rodríguez M, Oliva-Argüelles B, García I, Guillén-Pérez I, Palenzuela-Gardón D, Vázquez-Blomquist D, Falcón-Cama V, Mendoza-Fuentes O, Borras-Hidalgo O, Novoa-Pérez LI, Vázquez-Castillo M

Language: English
References: 11
Page: 328-331
PDF size: 276.98 Kb.

ABSTRACT

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 LALF_32-51 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 LALF_32-51 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 LALF_32-51. 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.

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