GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/43301 |
Resumo: | Brazilian 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). |
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Araújo, Taís Bacelar Sacramento deRocha, Leonardo de Oliveira Siquara daVidal, Manuela Torres AndionCoelho, Paulo Lucas CerqueiraReis, Mitermayer Galvão dosSouza, Bruno Solano de FreitasSoares, Milena Botelho PereiraPereira, Thiago AlmeidaColetta, Ricardo DellaBezerra, Daniel PereiraDias, Rosane BorgesRocha, Clarissa Araújo Gurgel2020-09-10T17:19:50Z2020-09-10T17:19:50Z2020ARAÚJO, 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, 2020.1661-6596https://www.arca.fiocruz.br/handle/icict/43301Brazilian 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).Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Propedeutics. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Propedeutics. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Propedeutics. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pathology. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Sao Rafael Hospital. D’Or Institute for Research and Education. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.Stanford University School of Medicine. Institute for Stem Cell Biology and Regenerative Medicine. Stanford, CA, USA.University of Campinas. School of Dentistry. Department of Oral Diagnosis. Piracicaba, SP, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Propedeutics. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Dentistry. Department of Propedeutics. Salvador, BA, Brazil / Federal University of Bahia. School of Medicine. Department of Pathology. Salvador, BA, Brazil.Due 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.engMDPINeoplasias oraisHedgehogInibidoresCâncerOral neoplasmsHedgehog signaling pathwayHedgehog signaling inhibitorsTargeted cancer therapyGANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/43301/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAraujo, T.B.S, GANT61.pdfAraujo, T.B.S, GANT61.pdfapplication/pdf3897303https://www.arca.fiocruz.br/bitstream/icict/43301/2/Araujo%2c%20T.B.S%2c%20GANT61.pdf2dc038b1b1bf1a4526bb17c067cde192MD52TEXTAraujo, T.B.S, GANT61.pdf.txtAraujo, T.B.S, GANT61.pdf.txtExtracted texttext/plain77625https://www.arca.fiocruz.br/bitstream/icict/43301/3/Araujo%2c%20T.B.S%2c%20GANT61.pdf.txt466a41ef33f89bd2ddc6e50c7dff5c71MD53icict/433012023-03-15 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| dc.title.pt_BR.fl_str_mv |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells |
| title |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells |
| spellingShingle |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells Araújo, Taís Bacelar Sacramento de Neoplasias orais Hedgehog Inibidores Câncer Oral neoplasms Hedgehog signaling pathway Hedgehog signaling inhibitors Targeted cancer therapy |
| title_short |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells |
| title_full |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells |
| title_fullStr |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells |
| title_full_unstemmed |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells |
| title_sort |
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells |
| author |
Araújo, Taís Bacelar Sacramento de |
| author_facet |
Araújo, Taís Bacelar Sacramento de Rocha, Leonardo de Oliveira Siquara da Vidal, Manuela Torres Andion Coelho, Paulo Lucas Cerqueira Reis, Mitermayer Galvão dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira Pereira, Thiago Almeida Coletta, Ricardo Della Bezerra, Daniel Pereira Dias, Rosane Borges Rocha, Clarissa Araújo Gurgel |
| author_role |
author |
| author2 |
Rocha, Leonardo de Oliveira Siquara da Vidal, Manuela Torres Andion Coelho, Paulo Lucas Cerqueira Reis, Mitermayer Galvão dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira Pereira, Thiago Almeida Coletta, Ricardo Della Bezerra, Daniel Pereira Dias, Rosane Borges Rocha, Clarissa Araújo Gurgel |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Araújo, Taís Bacelar Sacramento de Rocha, Leonardo de Oliveira Siquara da Vidal, Manuela Torres Andion Coelho, Paulo Lucas Cerqueira Reis, Mitermayer Galvão dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira Pereira, Thiago Almeida Coletta, Ricardo Della Bezerra, Daniel Pereira Dias, Rosane Borges Rocha, Clarissa Araújo Gurgel |
| dc.subject.other.pt_BR.fl_str_mv |
Neoplasias orais Hedgehog Inibidores Câncer |
| topic |
Neoplasias orais Hedgehog Inibidores Câncer Oral neoplasms Hedgehog signaling pathway Hedgehog signaling inhibitors Targeted cancer therapy |
| dc.subject.en.pt_BR.fl_str_mv |
Oral neoplasms Hedgehog signaling pathway Hedgehog signaling inhibitors Targeted cancer therapy |
| description |
Brazilian 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). |
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2020 |
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2020-09-10T17:19:50Z |
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2020-09-10T17:19:50Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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ARAÚJO, 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. |
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https://www.arca.fiocruz.br/handle/icict/43301 |
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1661-6596 |
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ARAÚJO, 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. 1661-6596 |
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MDPI |
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MDPI |
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