Journal Article

NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression

Lanza, Marika, Puliafito, Ivana, Esposito, Emanuela, Paterniti, Irene, Raciti, Gabriele, Casili, Giovanna, Scuderi, Sarah Adriana, Basilotta, Rossella, Filippone, Alessia, Colarossi, Lorenzo

2021

Overview

Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.

• Publisher: MDPI AG,MDPI
• Subject: Adapter proteins / Animals / Apoptosis / Carcinoma, Squamous Cell - drug therapy / Carcinoma, Squamous Cell - pathology / Cell Proliferation - drug effects / Cytokines / Disease Progression / Humans / Immune system / Inflammasomes - antagonists & inhibitors / Inflammasomes - metabolism / Male / Metastasis / Mice / Mice, Inbred BALB C / Mice, Nude / Mouth Neoplasms - drug therapy / Mouth Neoplasms - pathology / Nitriles - pharmacology / Nitriles - therapeutic use / NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors / NLR Family, Pyrin Domain-Containing 3 Protein - metabolism / Oral cancer / Pathogenesis / Squamous cell carcinoma / Sulfones - pharmacology / Sulfones - therapeutic use / Tumor Cells, Cultured / Xenograft Model Antitumor Assays