title: Identification of a novel antitumor peptide based on the screening of an Ala-library derived from the LALF(32-51) region.
abstract: Novel therapeutic peptides are increasingly making their way into clinical application. The cationic and amphipathic properties of certain peptides allow them to cross biological membranes in a non-disruptive way without apparent toxicity increasing drug bioavailability. By modifying the primary structure of the Limulus-derived LALF(32-51) peptide we designed a novel peptide, L-2, with antineoplastic effect and cell-penetrating capacity. Interestingly, L-2 induced cellular cytotoxicity in a variety of tumor cell lines and systemic injection into immunocompetent and nude mice bearing established solid tumor, resulted in substantial regression of the tumor mass and apoptosis. To isolate the gene transcripts specifically regulated by L-2 in tumor cells, we conducted suppressive subtractive hybridization (SSH) analysis and identified a set of genes involved in biological processes relevant to cancer biology. Our findings describe a novel peptide that modifies the gene expression of the tumor cells and exhibits antitumor effect in vivo, indicating that peptide L-2 is a potential candidate for anticancer therapy.
authors.affiliation: Department of Cancer, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Havana CP10600, Cuba.
authors.forename: Maribel G
authors.initials: MG
authors.lastname: Vallespi
authors.forename: Julio R
authors.initials: JR
authors.lastname: Fernandez
authors.forename: Isis
authors.initials: I
authors.lastname: Torrens
authors.forename: Isbel
authors.initials: I
authors.lastname: Garcia
authors.forename: Hilda
authors.initials: H
authors.lastname: Garay
authors.forename: Osmani
authors.initials: O
authors.lastname: Mendoza
authors.forename: Milaid
authors.initials: M
authors.lastname: Granadillo
authors.forename: Viviana
authors.initials: V
authors.lastname: Falcon
authors.forename: Boris
authors.initials: B
authors.lastname: Acevedo
authors.forename: Raimundo
authors.initials: R
authors.lastname: Ubieta
authors.forename: Gerardo E
authors.initials: GE
authors.lastname: Guillen
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Reyes
mesh_terms: D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000473:pathology*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D019151:Peptide Library; D010455:Peptides; D000409:Alanine