NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression
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, che...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/20/11108 |
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| author | Sarah Adriana Scuderi Giovanna Casili Rossella Basilotta Marika Lanza Alessia Filippone Gabriele Raciti Ivana Puliafito Lorenzo Colarossi Emanuela Esposito Irene Paterniti |
| author_facet | Sarah Adriana Scuderi Giovanna Casili Rossella Basilotta Marika Lanza Alessia Filippone Gabriele Raciti Ivana Puliafito Lorenzo Colarossi Emanuela Esposito Irene Paterniti |
| author_sort | Sarah Adriana Scuderi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:30:45Z |
| format | Article |
| id | doaj.art-61473c1b58e24377b729733d5c5aa0db |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:30:45Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-61473c1b58e24377b729733d5c5aa0db2023-11-22T18:34:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201110810.3390/ijms222011108NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma ProgressionSarah Adriana Scuderi0Giovanna Casili1Rossella Basilotta2Marika Lanza3Alessia Filippone4Gabriele Raciti5Ivana Puliafito6Lorenzo Colarossi7Emanuela Esposito8Irene Paterniti9Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 6 Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 6 Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 6 Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 6 Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 6 Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyIOM Ricerca Srl, Via Penninazzo 11, 95029 Catania, ItalyIstituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Catania, ItalyIstituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Catania, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 6 Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 6 Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, ItalyOral 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.https://www.mdpi.com/1422-0067/22/20/11108oral canceroral squamous cell carcinoma (OSCC)NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3)apoptosis |
| spellingShingle | Sarah Adriana Scuderi Giovanna Casili Rossella Basilotta Marika Lanza Alessia Filippone Gabriele Raciti Ivana Puliafito Lorenzo Colarossi Emanuela Esposito Irene Paterniti NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression International Journal of Molecular Sciences oral cancer oral squamous cell carcinoma (OSCC) NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) apoptosis |
| title | NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression |
| title_full | NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression |
| title_fullStr | NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression |
| title_full_unstemmed | NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression |
| title_short | NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression |
| title_sort | nlrp3 inflammasome inhibitor bay 117082 reduces oral squamous cell carcinoma progression |
| topic | oral cancer oral squamous cell carcinoma (OSCC) NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) apoptosis |
| url | https://www.mdpi.com/1422-0067/22/20/11108 |
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