Beneficial effect of KYP-2047, a propyl-oligopeptidase inhibitor, on oral squamous cell carcinoma

// Sarah Adriana Scuderi 1 , * , Giovanna Casili 1 , * , Alessia Filippone 1 , Marika Lanza 1 , Rossella Basilotta 1 , Raffaella Giuffrida 2 , Stefania Munaò 3 , Lorenzo Colarossi 3 , Anna Paola Capra 4 , Emanuela Esposito 1 and Irene Paterniti 1 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’ Alcontres, Messina 31-98166, ME, Italy 2 IOM Ricerca Srl, Viagrande 95029, CT, Italy 3 Istituto Oncologico del Mediterraneo, Viagrande 95029, CT, Italy 4 Department of Clinical and Experimental Medicine, University of Messina, Viale Ferdinando Stagno D’ Alcontres, Messina 31-98166, ME, Italy * These authors contributed equally to this work Correspondence to: Emanuela Esposito, email: eesposito@unime.it Keywords: oral squamous cell carcinoma (OSCC); tongue squamous cell carcinoma (TSCC); prolyl-oligopeptidase (POP); angiogenesis; apoptosis Received: September 02, 2021     Accepted: November 05, 2021     Published: December 07, 2021 Copyright: © 2021 Scuderi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Oral squamous cell-carcinoma (OSCC) is a common cancer which arises from the alveolar ridge, buccal mucosa, and tongue. Among OSCC, the incidence of tongue squamous cell-carcinoma (TSCC) is growing all over the world. Oral carcinogenesis has been linked to genetic mutations, chromosomal aberrations and viral factors. Apoptosis and angiogenesis play a key role in the development of oral cancer. Therefore, it is very important discover new therapeutic strategies to counteract oral cancer progression. This study aimed to investigate the effect of KYP-2047 in an in vitro model of TSCC and in vivo CAL27-xenograft model. Our results demonstrated that KYP-2047 was able to reduce TSCCs cell viability at the concentrations of 50 μM and 100 μM. Additionally, KYP-2047 was able to increase Bax, Bad and caspase-3 expression, whereas Bcl-2 and p53 expression were reduced. Moreover, KYP-2047 significantly reduced vascular-endothelial-growth-factor (VEGF) and endothelial-nitric-oxide-synthase (eNOS) expression. In the vivo xenograft model, KYP-2047 at doses of 1 and 5 mg/kg significantly reduced tumor burden and tumor weight, decreasing also angiogenesis markers VEGF and eNOS. Moreover, KYP-2047 increased Bax and reduced Bcl2 expressions. Thus, KYP-2047 could represent a potential therapeutic treatment to counteract tongue oral-cancer growth, thanks its abilities to modulate angiogenesis and apoptosis pathways.