title: RGDechi-hCit: αvβ3 selective pro-apoptotic peptide as potential carrier for drug delivery into melanoma metastatic cells.
abstract: αvβ3 integrin is an important tumor marker widely expressed on the surface of cancer cells. Recently, we reported some biological features of RGDechi-hCit, an αvβ3 selective peptide antagonist. In the present work, we mainly investigated the pro-apoptotic activity of the molecule and its ability to penetrate the membrane of WM266 cells, human malignant melanoma cells expressing high levels of αvβ3 integrin. For the first time we demonstrated the pro-apoptotic effect and the ability of RGDechi-hCit to enter into cell overexpressing αvβ3 integrin mainly by clathrin- and caveolin-mediated endocytosis. Furthermore, we deepened and confirmed the selectivity, anti-adhesion, and anti-proliferative features of the peptide. Altogether these experiments give insight into the biological behavior of RGDechi-hCit and have important implications for the employment of the peptide as a new selective carrier to deliver drugs into the cell and as a therapeutic and diagnostic tool for metastatic melanoma. Moreover, since the peptide shows a pro-apoptotic effect, a great perspective could be the development of a new class of selective systems containing RGDechi-hCit and pro-apoptotic molecules or other therapeutic agents to attain a synergic action.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Capasso
authors.affiliation: Institute of Biostructures and Bioimaging -CNR, Naples, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: de Paola
authors.affiliation: Diagnostic and Molecular Pharmaceutics -Scarl, Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Liguoro
authors.affiliation: Institute of Biostructures and Bioimaging -CNR, Naples, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Del Gatto
authors.affiliation: Institute of Biostructures and Bioimaging -CNR, Naples, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Di Gaetano
authors.affiliation: Center for Advanced Biomaterials for Health Care @ CRIB- Italian Institute of Technology, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Guarnieri
authors.affiliation: Institute of Crystallography -CNR, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.affiliation: Institute of Biostructures and Bioimaging -CNR, Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zaccaro
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis; D022461:Caveolins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002966:Clathrin / Q000378:metabolism; D004337:Drug Carriers / Q000494:pharmacology / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D022461:Caveolins; D002966:Clathrin; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D010455:Peptides; C581099:RGDechi-hCit peptide