A Novel Small Peptide Inhibitor of NFB, RH10, Blocks Oxidative Stress-Dependent Phenotypes in Cancer.

Authors:
Michele Ciccarelli
Michele Ciccarelli
University of Salerno
Fisciano | Italy
Antonella Fiordelisi
Antonella Fiordelisi
Federico II University
Marina Sala
Marina Sala
University of Naples Federico II
Italy
Roberto Pacelli
Roberto Pacelli
Institute of Biostructures and Bioimaging
Italy
Pietro Campiglia
Pietro Campiglia
University of Salerno

Oxid Med Cell Longev 2018 4;2018:5801807. Epub 2018 Nov 4.

Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy.

Background: The RH domain of GRK5 is an effective modulator of cancer growth through the inhibition of NFB 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 NFB signaling and its dependent phenotypes were evaluated by Western blot, TUNEL assay, proliferation assay, and angiogenesis . 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 IB, to increase IB levels, to induce apoptosis, to inhibit KAT4-cell proliferation, NFB activation, ROS production, and angiogenesis . , 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.

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Source
http://dx.doi.org/10.1155/2018/5801807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247396PMC
January 2019
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