Rgdechi-Hcit: Alpha V Beta 3 Selective Pro-Apoptotic Peptide As Potential Carrier For Drug Delivery Into Melanoma Metastatic Cells(454 views) Capasso D, De Paola I, Liguoro A, Del Gatto A, Di Gaetano S, Guarnieri D, Saviano M, Zaccaro L
Keywords: Antineoplastic Agent, Caveolin, Clathrin, Drug Carrier, Polypeptide, Rgdechi Hcit Peptide, Unclassified Drug, Vitronectin Receptor, Adenocarcinoma Cell Line, Antineoplastic Activity, Antiproliferative Activity, Article, Binding Affinity, Binding Site, Cell Adhesion, Cell Assay, Cell Proliferation, Confocal Microscopy, Controlled Study, Drug Cytotoxicity, Drug Delivery System, Drug Effect, Drug Mechanism, Endocytosis, Flow Cytometry, Human, Human Cell, Melanoma Cell Line, Molecular Interaction, Protein Expression, Wm266 Cell Line,
Affiliations: *** IBB - CNR ***
Department of Pharmacy, University of Naples Federico IINaples, Italy
Institute of Biostructures and Bioimaging -CNRNaples, Italy
Diagnostic and Molecular Pharmaceutics -ScarlNaples, Italy
Center for Advanced Biomaterials for Health Care at CRIB, Italian Institute of TechnologyNaples, Italy
Institute of Crystallography-CNRBari, Italy
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Aguzzi, M. S., D'Arcangelo, D., Giampietri, C., Capogrossi, M. C., Facchiano, A., RAM, an RGDS analog, exerts potent anti-melanoma effects in vitro and in vivo (2011) PloS One, 6, p. e25352
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Reardon, D. A., Neyns, B., Weller, M., Tonn, J. C., Nabors, L. B., Cilengitide: An RGD pentapeptide alphanubeta3 and alphanubeta5 integrin inhibitor in development for glioblastoma and other malignancies (2011) Future Oncology, 7, pp. 339-354
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Haass, N. K., Smalley, K. S., Li, L., Herlyn, M., Adhesion, migration and communication in melanocytes and melanoma (2005) Pigment Cell Research/ Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society, 18, pp. 150-159
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McGary, E. C., Lev, D. C., Bar-Eli, M., Cellular adhesion pathways and metastatic potential of human melanoma (2002) Cancer Biology & Therapy, 1, pp. 459-465
Jilaveanu, L. B., Aziz, S. A., Kluger, H. M., Chemotherapy and biologic therapies for melanoma: Do they work? (2009) Clinics in Dermatology, 27, pp. 614-625
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Alam, M. R., Dixit, V., Kang, H., Li, Z. B., Chen, X., Intracellular delivery of an anionic antisense oligonucleotide via receptor-mediated endocytosis (2008) Nucleic Acids Research, 36, pp. 2764-2776
Plow, E. F., Cierniewski, C. S., Xiao, Z., Haas, T. A., Byzova, T. V., AlphaIIbbeta3 and its antagonism at the new millennium (2001) Thrombosis and Haemostasis, 86, pp. 34-40
White, D. E., Muller, W. J., Multifaceted roles of integrins in breast cancer metastasis (2007) Journal of Mammary Gland Biology and Neoplasia, 12, pp. 135-142
Ellerby, H. M., Arap, W., Ellerby, L. M., Kain, R., Andrusiak, R., Anticancer activity of targeted pro-apoptotic peptides (1999) Nature Medicine, 5, pp. 1032-1038
Andersen, M. H., Svane, I. M., Becker, J. C., Straten, P. T., The universal character of the tumor-associated antigen survivin (2007) Clinical Cancer Research An Official Journal of the American Association for Cancer Research, 13, pp. 5991-5994
Adderley, S. R., Fitzgerald, D. J., Glycoprotein IIb/IIIa antagonists induce apoptosis in rat cardiomyocytes by caspase-3 activation (2000) The Journal of Biological Chemistry, 275, pp. 5760-5766
Mizejewski, G. J., Role of integrins in cancer: Survey of expression patterns (1999) Proceedings of the Society for Experimental Biology and Medicine Society for Experimental Biology and Medicine, 222, pp. 124-138
Aguzzi, M. S., Fortugno, P., Giampietri, C., Ragone, G., Capogrossi, M. C., Intracellular targets of RGDS peptide in melanoma cells (2010) Molecular Cancer, 9, p. 84
Frisch, S. M., Ruoslahti, E., Integrins and anoikis (1997) Current Opinion in Cell Biology, 9, pp. 701-706
Rgdechi-Hcit: Alpha V Beta 3 Selective Pro-Apoptotic Peptide As Potential Carrier For Drug Delivery Into Melanoma Metastatic Cells
alpha v beta 3 integrin is an important tumor marker widely expressed on the surface of cancer cells. Recently, we reported some biological features of RGDechi-hCit, an alpha v beta 3 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 alpha v beta 3 integrin. For the first time we demonstrated the pro-apoptotic effect and the ability of RGDechi-hCit to enter into cell overexpressing alpha v beta 3 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
Rgdechi-Hcit: Alpha V Beta 3 Selective Pro-Apoptotic Peptide As Potential Carrier For Drug Delivery Into Melanoma Metastatic Cells
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