Abstract 234: Inhibition of the NOTCH transcription factor complex by a novel hybrid protein leads to effective tumor therapy.

The Notch pathway has been implicated in the generation and propagation of cancer stem cells and is thus an attractive target for therapy. We have generated a hybrid protein (Antp-DNMAML) consisting of the truncated version of Mastermind‐like (MAML) that behaves in a dominant negative (DN) fashion inhibiting Notch, and the cell penetrating peptide Antennapedia (Antp). Results indicate that the Antp-DNMAML translocates into the nucleus, suppresses Notch activation, reverts the transformed phenotype, inhibits the anchorage‐dependent growth and induces self contact inhibition and apoptosis in tumorigenic human breast cancer cells. More significantly, there is direct evidence that inhibiting Notch signaling at the transcriptional level with the Antp-DNMAML protein, suppresses the expression of downstream Notch targets and inhibits tumor growth in nude mice, without organ or systemic toxicity. In summary, intracellular delivery of dominant-negative transcription complex proteins using the Antp platform is a new and specific approach for cancer therapy . Citation Format: Agamemnon A. Epenetos, Christina Kousparou, Spyros Stylianou, Mahendra Deonarain, Aleksandra Filipovic. Inhibition of the NOTCH transcription factor complex by a novel hybrid protein leads to effective tumor therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 234. doi:10.1158/1538-7445.AM2013-234