Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)

Oral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer and it is characterized by a high metastasis grade. The aim of this study was to evaluate for the first time the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and...

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Main Authors: Giovanna Casili, Sarah Adriana Scuderi, Marika Lanza, Alessia Filippone, Deborah Mannino, Raffaella Giuffrida, Cristina Colarossi, Marzia Mare, Anna Paola Capra, Federica De Gaetano, Marco Portelli, Angela Militi, Salvatore Cuzzocrea, Irene Paterniti, Emanuela Esposito
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/10/2796
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author Giovanna Casili
Sarah Adriana Scuderi
Marika Lanza
Alessia Filippone
Deborah Mannino
Raffaella Giuffrida
Cristina Colarossi
Marzia Mare
Anna Paola Capra
Federica De Gaetano
Marco Portelli
Angela Militi
Salvatore Cuzzocrea
Irene Paterniti
Emanuela Esposito
author_facet Giovanna Casili
Sarah Adriana Scuderi
Marika Lanza
Alessia Filippone
Deborah Mannino
Raffaella Giuffrida
Cristina Colarossi
Marzia Mare
Anna Paola Capra
Federica De Gaetano
Marco Portelli
Angela Militi
Salvatore Cuzzocrea
Irene Paterniti
Emanuela Esposito
author_sort Giovanna Casili
collection DOAJ
description Oral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer and it is characterized by a high metastasis grade. The aim of this study was to evaluate for the first time the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and its role in the invasiveness and metastasis processes in neighbor organs such as lymph node, lung, and spleen tissues. Our results demonstrated that BAY-117082 treatment, at doses of 2.5 mg/kg and 5 mg/kg, was able to significantly reduce the presence of microscopic tumor islands and nuclear pleomorphism in tongue tissues and modulate the NLRP3 inflammasome pathway activation in tongue tissues, as well as in metastatic organs such as lung and spleen. Additionally, BAY-117082 treatment modulated the epithelial–mesenchymal transition (EMT) process in tongue tissue as well as in metastatic organs such as lymph node, lung, and spleen, also reducing the expression of matrix metalloproteinases (MMPs), particularly MMP2 and MMP9, markers of cell invasion and migration. In conclusion, the obtained data demonstrated that BAY-117082 at doses of 2.5 mg/kg and 5 mg/kg were able to reduce the tongue tumor area as well as the degree of metastasis in lymph node, lung, and spleen tissues through the NLRP3 inflammasome pathway inhibition.
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spelling doaj.art-b4a45d9ba9a64b7ea195f86e1923e2162023-11-18T00:49:07ZengMDPI AGCancers2072-66942023-05-011510279610.3390/cancers15102796Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)Giovanna Casili0Sarah Adriana Scuderi1Marika Lanza2Alessia Filippone3Deborah Mannino4Raffaella Giuffrida5Cristina Colarossi6Marzia Mare7Anna Paola Capra8Federica De Gaetano9Marco Portelli10Angela Militi11Salvatore Cuzzocrea12Irene Paterniti13Emanuela Esposito14Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyIOM Ricerca, Via Penninazzo 11, 95029 Viagrande Catania, ItalyIOM Ricerca, Via Penninazzo 11, 95029 Viagrande Catania, ItalyIOM Ricerca, Via Penninazzo 11, 95029 Viagrande Catania, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Biomedical and Dental Science, Morphological and Functional Images, University of Messina, Via Consolare Valeria, 98125 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31, 98166 Messina, ItalyOral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer and it is characterized by a high metastasis grade. The aim of this study was to evaluate for the first time the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and its role in the invasiveness and metastasis processes in neighbor organs such as lymph node, lung, and spleen tissues. Our results demonstrated that BAY-117082 treatment, at doses of 2.5 mg/kg and 5 mg/kg, was able to significantly reduce the presence of microscopic tumor islands and nuclear pleomorphism in tongue tissues and modulate the NLRP3 inflammasome pathway activation in tongue tissues, as well as in metastatic organs such as lung and spleen. Additionally, BAY-117082 treatment modulated the epithelial–mesenchymal transition (EMT) process in tongue tissue as well as in metastatic organs such as lymph node, lung, and spleen, also reducing the expression of matrix metalloproteinases (MMPs), particularly MMP2 and MMP9, markers of cell invasion and migration. In conclusion, the obtained data demonstrated that BAY-117082 at doses of 2.5 mg/kg and 5 mg/kg were able to reduce the tongue tumor area as well as the degree of metastasis in lymph node, lung, and spleen tissues through the NLRP3 inflammasome pathway inhibition.https://www.mdpi.com/2072-6694/15/10/2796oral cancerNLRP3metastasislymph nodespleenlung
spellingShingle Giovanna Casili
Sarah Adriana Scuderi
Marika Lanza
Alessia Filippone
Deborah Mannino
Raffaella Giuffrida
Cristina Colarossi
Marzia Mare
Anna Paola Capra
Federica De Gaetano
Marco Portelli
Angela Militi
Salvatore Cuzzocrea
Irene Paterniti
Emanuela Esposito
Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)
Cancers
oral cancer
NLRP3
metastasis
lymph node
spleen
lung
title Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)
title_full Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)
title_fullStr Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)
title_full_unstemmed Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)
title_short Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)
title_sort therapeutic potential of bay 117082 a selective nlrp3 inflammasome inhibitor on metastatic evolution in human oral squamous cell carcinoma oscc
topic oral cancer
NLRP3
metastasis
lymph node
spleen
lung
url https://www.mdpi.com/2072-6694/15/10/2796
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