Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition
Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2777 |
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| author | Rossella Basilotta Marika Lanza Alessia Filippone Giovanna Casili Deborah Mannino Federica De Gaetano Giulia Chisari Lorenzo Colarossi Gianmarco Motta Michela Campolo Salvatore Cuzzocrea Irene Paterniti Emanuela Esposito |
| author_facet | Rossella Basilotta Marika Lanza Alessia Filippone Giovanna Casili Deborah Mannino Federica De Gaetano Giulia Chisari Lorenzo Colarossi Gianmarco Motta Michela Campolo Salvatore Cuzzocrea Irene Paterniti Emanuela Esposito |
| author_sort | Rossella Basilotta |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this reason, it is necessary to investigate new therapeutic strategies to counteract the progression of OSCC. In this study, we aimed to evaluate the role of dimethyl fumarate (DMF) in modulation of OSCC progression, both in vitro and in an in vivo orthotopic xenograft model. In vitro results revealed that DMF was able to reduce the expression of anti-apoptotic factors as BCL-2 and increased the expression of pro-apoptotic factors as Bax, Caspase-3 and BID. DMF appears to be involved in the modulation of oxidative stress mediators, such as MnSOD and HO-1. Furthermore, DMF showed to reduce the migratory ability of tumor cells and to modulate the expression of markers of epithelial-mesenchymal transition (EMT), as N-cadherin and E-cadherin. The in vivo study confirmed the data obtained in vitro significantly decreasing tumor mass and also reducing oxidative stress and apoptosis. Therefore, based on these results, the use of DMF could be considered a promising strategy to counteract oral cancer progression. |
| first_indexed | 2024-03-11T09:40:08Z |
| format | Article |
| id | doaj.art-aa0c09cc009a49b292f0219ad1084e4b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:40:08Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aa0c09cc009a49b292f0219ad1084e4b2023-11-16T17:02:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243277710.3390/ijms24032777Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal TransitionRossella Basilotta0Marika Lanza1Alessia Filippone2Giovanna Casili3Deborah Mannino4Federica De Gaetano5Giulia Chisari6Lorenzo Colarossi7Gianmarco Motta8Michela Campolo9Salvatore Cuzzocrea10Irene Paterniti11Emanuela Esposito12Department 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, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, 98166 Messina, ItalyIstituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Viagrande, ItalyIstituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Viagrande, ItalyIstituto Oncologico del Mediterraneo, Via Penninazzo 7, 95029 Viagrande, 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 common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this reason, it is necessary to investigate new therapeutic strategies to counteract the progression of OSCC. In this study, we aimed to evaluate the role of dimethyl fumarate (DMF) in modulation of OSCC progression, both in vitro and in an in vivo orthotopic xenograft model. In vitro results revealed that DMF was able to reduce the expression of anti-apoptotic factors as BCL-2 and increased the expression of pro-apoptotic factors as Bax, Caspase-3 and BID. DMF appears to be involved in the modulation of oxidative stress mediators, such as MnSOD and HO-1. Furthermore, DMF showed to reduce the migratory ability of tumor cells and to modulate the expression of markers of epithelial-mesenchymal transition (EMT), as N-cadherin and E-cadherin. The in vivo study confirmed the data obtained in vitro significantly decreasing tumor mass and also reducing oxidative stress and apoptosis. Therefore, based on these results, the use of DMF could be considered a promising strategy to counteract oral cancer progression.https://www.mdpi.com/1422-0067/24/3/2777OSCCDMFoncologyoxidative stressapoptosisEMT |
| spellingShingle | Rossella Basilotta Marika Lanza Alessia Filippone Giovanna Casili Deborah Mannino Federica De Gaetano Giulia Chisari Lorenzo Colarossi Gianmarco Motta Michela Campolo Salvatore Cuzzocrea Irene Paterniti Emanuela Esposito Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition International Journal of Molecular Sciences OSCC DMF oncology oxidative stress apoptosis EMT |
| title | Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition |
| title_full | Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition |
| title_fullStr | Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition |
| title_full_unstemmed | Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition |
| title_short | Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition |
| title_sort | therapeutic potential of dimethyl fumarate in counteract oral squamous cell carcinoma progression by modulating apoptosis oxidative stress and epithelial mesenchymal transition |
| topic | OSCC DMF oncology oxidative stress apoptosis EMT |
| url | https://www.mdpi.com/1422-0067/24/3/2777 |
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