title: Antitumor effect of RGD-4C-GG-D(KLAKLAK)2 peptide in mouse B16(F10) melanoma model.
abstract: Vasculature targeting agents have been tested as cancer therapeutics for the past few years. Such therapy could be accomplished using, for example, bifunctional (two-domain) peptides. RGD-4C-GG-D(KLAKLAK)2, a peptide designed by Ellerby and coworkers (1999) (full sequence: ACDCRGDCFCGGKLAKLAKKLAKLAK), binds selectively to alphaVbeta3 integrin receptors expressed in tumor neovasculature and, after internalization, effectively induces apoptosis of endothelial cells. The aim of this study was to examine if RGD-4C-GG-D(KLAKLAK)2 would efficiently target cells, among them B16(F10), that overexpress alphaVbeta3 receptors, and whether it would be suitable for therapeutic treatment of primary B16(F10) murine melanoma tumors. Thus, the peptide would target two distinct tumor compartments: that formed by endothelium of blood vessels and that made up of neoplastic cells. The therapeutic peptide was recognized and did induce apoptosis in B16(F10) cell line. Tumor growth inhibition was observed following direct intratumoral administration. However, cessation of peptide administration led to rapid tumor growth and death of the animals.
authors.affiliation: Department of Molecular Biology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Smolarczyk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cichoń
authors.forename: Klaudyna
authors.initials: K
authors.lastname: Graja
authors.forename: Joanna
authors.initials: J
authors.lastname: Hucz
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sochanik
authors.forename: Stanisław
authors.initials: S
authors.lastname: Szala
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D009842:Oligopeptides / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid