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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.

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