A Novel Small Peptide Inhibitor of NFκB, RH10, Blocks Oxidative Stress-Dependent Phenotypes in Cancer. (4th November 2018)

• Record Type: Journal Article
• Authors: Gambardella, Jessica; Ciccarelli, Michele; Del Giudice, Carmine; Fiordelisi, Antonella; De Rosa, Matteo; Sala, Marina; Pacelli, Roberto; Campiglia, Pietro; Trimarco, Bruno; Iaccarino, Guido; Sorriento, Daniela
• Other Names: Sartiani Laura Guest Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2018(2018)
• Publication Date: 2018-11-04
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2018/5801807
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Background . The RH domain of GRK5 is an effective modulator of cancer growth through the inhibition of NF κ B activity. The aim of this study was to identify the minimum effective sequence of RH that is still able to inhibit tumor growth and could be used as a peptide-based drug for therapy. Methods . Starting from the RH sequence, small peptides were cloned and tested in KAT-4 cells. The effects on NF κ B signaling and its dependent phenotypes were evaluated by Western blot, TUNEL assay, proliferation assay, and angiogenesis in vitro . In vivo experiments were performed in KAT-4 xenografts in Balb/c nude mice. Results . A minimum RH ten amino acids long sequence (RH10) was able to interact with I κ B, to increase I κ B levels, to induce apoptosis, to inhibit KAT4-cell proliferation, NF κ B activation, ROS production, and angiogenesis in vitro . In vivo, the peptide inhibited tumor growth in a dose-dependent manner. We also tested its effects in combination with chemotherapeutic drugs and radiotherapy. RH10 ameliorated the antitumor responses to cisplatin, doxorubicin, and ionizing radiation. Conclusion . Our data propose RH10 as a potential peptide-based drug to use for cancer treatment both alone or in combination with anticancer therapies.