Anticancer properties of the fatty acid synthase inhibitor TVB-3166 on oral squamous cell carcinoma cell lines

Iara Gonçalves de Aquino; Débora Campanella Bastos; Florence Juana Maria Cuadra-Zelaya; Isadora Ferrari Teixeira; Tuula Salo; Ricardo Della Coletta; Edgard Graner

doi:10.1016/j.archoralbio.2020.104707

Anticancer properties of the fatty acid synthase inhibitor TVB-3166 on oral squamous cell carcinoma cell lines

Arch Oral Biol. 2020 May:113:104707. doi: 10.1016/j.archoralbio.2020.104707. Epub 2020 Mar 10.

Authors

Iara Gonçalves de Aquino¹, Débora Campanella Bastos², Florence Juana Maria Cuadra-Zelaya¹, Isadora Ferrari Teixeira¹, Tuula Salo³, Ricardo Della Coletta¹, Edgard Graner⁴

Affiliations

¹ Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, Sao Paulo, Brazil.
² Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, Sao Paulo, Brazil; Department of Morphology, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, Sao Paulo, Brazil.
³ Cancer and Translational Medicine Research Unit, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Institute of Oral and Maxillofacial Disease, University of Helsinki, and HUSLAB, Department of Pathology, Helsinki University Hospital, Helsinki, Finland.
⁴ Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, Sao Paulo, Brazil. Electronic address: graner@unicamp.br.

PMID: 32197133
DOI: 10.1016/j.archoralbio.2020.104707

Abstract

Objective: Fatty acid synthase (FASN) is overexpressed in several human cancers, including oral squamous cell carcinoma (OSCC). TVB-3166 is a recently described FASN inhibitor with antitumor effects and potential clinical relevance. The objective of this study was to evaluate the effects of TVB-3166 on OSCC cell lines.

Materials and methods: The OSCC cell line SCC-9 modified to express ZsGreen (ZsG) (SCC-9 ZsG) and its in vivo selected metastatic derivative LN-1A were used to evaluate anticancer properties of TVB-3166. Cell viability was determined using MTT assays and proliferation determined by cell counting in a Neubauer chamber. Cell death and cell cycle progression were analyzed by Annexin V-PE/7-ADD-PerCP labeling and PI staining, respectively. Cell migration was assayed by scratch assays and cell adhesion using myogel. Production of FASN, p-AKT, CPT1-α, and epithelial-mesenchymal transition (EMT) markers were examined by Western blotting.

Results: TVB-3166 significantly reduced cell viability and proliferation, promoted cell cycle arrest and apoptosis, and increased adhesion to myogel in both OSCC cell lines. Finally, the drug reduced SCC-9 ZsG migration.

Conclusion: Our results demonstrated that TVB-3166 has anticancer effects on both SCC-9 ZsG and its metastatic version LN-1A, which are worthy of investigation in preclinical models for OSCC.

Keywords: Cell lines; Fatty acid synthase; Oral squamous cell carcinoma; TVB-3166.

MeSH terms

Apoptosis
Azetidines / pharmacology*
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / pathology*
Cell Line, Tumor
Cell Movement
Cell Proliferation
Fatty Acid Synthases / antagonists & inhibitors*
Humans
Mouth Neoplasms / drug therapy
Mouth Neoplasms / pathology*
Nitriles / pharmacology*
Pyrazoles / pharmacology*

Substances

4-(1-(5-(3,4-dimethyl-1H-pyrazol-5-yl)-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrile
Azetidines
Nitriles
Pyrazoles
Fatty Acid Synthases