Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial-Mesenchymal Transition

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2777
• Main Authors: Basilotta, Rossella, Lanza, Marika, Filippone, Alessia, Casili, Giovanna, Mannino, Deborah, De Gaetano, Federica, Chisari, Giulia, Colarossi, Lorenzo, Motta, Gianmarco, Campolo, Michela, Cuzzocrea, Salvatore, Paterniti, Irene, Esposito, Emanuela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Antioxidants; Apoptosis; Bcl-2 protein; Buccal mucosa; Cancer therapies; Carcinoma, Squamous Cell - pathology; Caspase-3; Cell adhesion & migration; Cell Line, Tumor; Cell Proliferation; Chemotherapy; Dimethyl Fumarate - pharmacology; Dimethyl Fumarate - therapeutic use; DMF; E-cadherin; EMT; Epithelial-Mesenchymal Transition; Head and Neck Neoplasms; Humans; In vivo methods and tests; Lymphoma; Medical prognosis; Mesenchyme; Mouth Neoplasms - pathology; N-Cadherin; oncology; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; OSCC; Oxidative Stress; Proteins; Radiation therapy; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Tumor cells; Tumors; Xenografts; Xenotransplantation; OSCC; apoptosis; DMF; EMT; oncology; oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032777

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.