GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells

dc.creatorAraújo, Taís Bacelar Sacramento de
dc.creatorRocha, Leonardo de Oliveira Siquara da
dc.creatorVidal, Manuela Torres Andion
dc.creatorCoelho, Paulo Lucas Cerqueira
dc.creatorReis, Mitermayer Galvão dos
dc.creatorSouza, Bruno Solano de Freitas
dc.creatorSoares, Milena Botelho Pereira
dc.creatorPereira, Thiago Almeida
dc.creatorColetta, Ricardo Della
dc.creatorBezerra, Daniel Pereira
dc.creatorDias, Rosane Borges
dc.creatorRocha, Clarissa Araújo Gurgel
dc.date2020-09-10T17:19:50Z
dc.date2020-09-10T17:19:50Z
dc.date2020
dc.date.accessioned2023-09-26T22:23:00Z
dc.date.available2023-09-26T22:23:00Z
dc.identifierARAÚJO, Taís Bacelar Sacramento de et al. GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells. International Journal of Molecular Sciences, 2020.
dc.identifier1661-6596
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/43301
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8878537
dc.descriptionBrazilian research funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-309380/2015-4) and Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB-APP0006/2016).
dc.descriptionDue to its importance in the pathogenesis of oral squamous cell carcinoma (OSCC), the Hedgehog (HH) pathway is considered a potential therapeutic target. We investigated the e ects of GANT61, a GLI inhibitor, on HH gene expression, as well as on metastatic OSCC cell proliferation and death. Following culture in DMEM medium, cytotoxicity of GANT61 against di erent tumor and non-tumor cell types was assessed by alamarBlue assays. Cytotoxicity analysis revealed that the metastatic HSC3 cell line was the most sensitive (IC50: 36 M) to the tested compound. The compound’s e ects on the expression of HH pathways components were analyzed by qPCR and Western blot; cell viability was analyzed by trypan blue assay and flow cytometry were used to investigate cell cycle phase, morphology, and death patterns in HSC3 cells. A significant reduction in mRNA levels of the GLI1 transcription factor was found after 12 h of treatment withGANT61. Protein expression levels of other HH pathway components (PTCH1, SHH, and Gli1) and HSC3 cell viability also decreased after 24 h of treatment. Cell cycle analysis and death pattern evaluations revealed significantly increased nuclear fragmentation in sub-G1 phase, as well as cell death due to apoptosis. In conclusion, the significantly reduced GLI1 gene expression seen in response to the GLI inhibitor indicates diminished downstream activation in HH pathway components. GANT61 significantly reduced cell viability in the metastatic cell line of OSCC and promoted a significant increase in nuclear fragmentation and cell death by apoptosis.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.rightsopen access
dc.subjectNeoplasias orais
dc.subjectHedgehog
dc.subjectInibidores
dc.subjectCâncer
dc.subjectOral neoplasms
dc.subjectHedgehog signaling pathway
dc.subjectHedgehog signaling inhibitors
dc.subjectTargeted cancer therapy
dc.titleGANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells
dc.typeArticle


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