Irene Paterniti

University of Messina, Messina, Italy

Title: KYP-2047, an Inhibitor of Prolyl-Oligopeptidase, Reduces Glioblastoma Proliferation through Angiogenesis and Apoptosis Modulation

---

Biography

Dr Irene Paterniti primary research interest is addressed to investigate the mechanisms of neurodegeneration and neuroinflammation common to many neurological disorders including Alzheimer and Parkinson’s disease, Motor Neuron diseases and Brain Injury. Dr Irene Paterniti is graduated in Biology at the University of Messina in 2008. She has completed her PhD in “Experimental Medicine” at Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina in 2011. Moreover, she worked as visiting Scientist at Centre for Neuroscience and Trauma Blizard Institute of Cell and Molecular Science” Barts and The London School of Medicine and Dentistry, London-UK. Her studies aim to investigate and discover new molecular target for the development of new therapeutic strategies for neurodegenerative diseases treatment.

Abstract

Glioblastoma (GB) is the most aggressive tumor of the central nervous system (CNS). GB is characterized by excessive proliferation, metastasis, invasiveness and necrosis. Currently, the standard treatment for GB includes surgical removal of tumor, followed by chemotherapy and radiotherapy. However, the survival rate for patients with GB still remains low; therefore, the discovery of new molecular target represents an important goal for cancer research. Angiogenesis and apoptosis play a key role in the development of GB. Thus, the modulation of angiogenesis and apoptosis processes could be a possible strategy to reduce or arrest GB progression. The aim of this study was to investigate the potential effect of KYP-2047, an inhibitor of the prolyl-oligopeptidase (POP or PREP), known to modulate angiogenesis process, in an in vivo U87-xenograft model and in an in vitro model on human GB cells. Our results showed that KYP-2047 at doses of 2.5 mg/kg and 5 mg/kg was able to reduce subcutaneous tumor mass, tumor burden as well as tumor weight in the xenograft-model. Moreover, KYP-2047 significantly reduced vascular endothelial-growth-factor (VEGF), angiopoietin1 (Ang1), angiopoietin2 (Ang2) and endothelial-nitric-oxide synthase (eNOS) expression, counteracting angiogenesis process. Furthermore, in vitro study revealed that KYP-2047 at different concentrations significantly reduced U87, U138 and A172 GB cells viability. Additionally, KYP-2047 at the concentrations of 50 µM and 100 µM was able to increase the pro-apoptotic protein Bax, p53 and caspase-3 expression whereas Bcl-2 expression was significantly reduced. Thus, based on these results, KYP-2047 could represent a potential therapeutic treatment to counteract or reduce GB progression, thanks its abilities to modulate angiogenesis and apoptosis pathway through POP inhibition.