Boelcke, W. P., Teixeira, I. F., Aquino, I. G., Mazzaro, A. R., Cuadra-Zelaya, F. J. M., de Souza, A. P., Salo, T., Della Coletta, R., Graner, E., & Bastos, D. C. (2022). Pharmacological fatty acid synthase inhibitors differently affect the malignant phenotype of oral cancer cells. Archives of Oral Biology, 135, 105343. https://doi.org/10.1016/j.archoralbio.2021.105343
Pharmacological fatty acid synthase inhibitors differently affect the malignant phenotype of oral cancer cells
|Author:||Boelcke, Willian Peter1,2; Teixeira, Isadora Ferrari2; Aquino, Iara Gonçalves2;|
1Department of Biociences, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil
2Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil
3Department of Pathology, University of El Salvador, San Salvador, El Salvador
4Cancer and Translational Medicine Research Unit, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
5Institute of Oral and Maxillofacial Disease, University of Helsinki, and HUSLAB, Department of Pathology, Helsinki University Hospital, Helsinki, Finland
|Online Access:||PDF Full Text (PDF, 0.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022121972526
|Publish Date:|| 2022-12-28
Objectives: Fatty acid synthase levels are associated with aggressiveness, prognosis, and risk of metastasis in oral squamous cell carcinomas. This enzyme contains seven catalytic domains and its inhibition by synthetic or natural drugs has antineoplastic properties such as C75, which is a synthetic inhibitor of the β- ketoacyl synthase domain, the antibiotic triclosan, ligand of the enoyl reductase domain, and the antiobesity drug orlistat, which inhibits the thioesterase domain. Here, we sought to investigate and compare the in vitro effects of C75, triclosan, and orlistat on malignant phenotypes of the cell line SCC-9: proliferation, cell cycle, apoptosis, adhesion, migration, and invasion.
Design: Half-maximal inhibitory concentration (IC50) was determined using cell viability assays. Cell death and cell cycle progression were analyzed by Annexin V-PE/7-ADD-PerCP labeling and propidium iodide staining, respectively. Cell migration and invasion were assayed by transwells assays and cell adhesion using collagen and fibronectin.
Results: C75 showed the lowest IC50 and higher inhibition of lipid droplets at low concentrations and reduced cell motility. Triclosan showed the intermediate IC50 value, excellent reduction of lipid bodies at the IC50 when compared with C75 and orlistat. Also, triclosan reduced cell cycle progression, adhesion, migration, and invasion of SCC-9 and induced the highest levels of apoptosis. Orlistat promoted cell cycle arrest, but showed the lowest induction of apoptosis and did not affected invasion and adhesion of SCC-9.
Conclusions: Altogether, despite the particular effects of the analyzed fatty acid synthase inhibitors, triclosan showed to better interfere in tumorigenic phenotypes of SCC-9 cells.
Archives of oral biology
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo - Brazil (FAPESP, 2014/20832-3, 2016/07129-7 and 2016/24906-7) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES - 8882.306833/2018–0 and 8887.352647/2019–0).
© 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/