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GANT61 REDUCES HEDGEHOG MOLECULE (GLI1) EXPRESSION AND PROMOTES APOPTOSIS IN METASTATIC ORAL SQUAMOUS CELL CARCINOMA CELLS
Hedgehog signaling pathway
Hedgehog signaling inhibitors
Targeted cancer therapy
Autor
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
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
Afiliación
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.
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.
Resumen en ingles
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.
Palabras clave en ingles
Oral neoplasmsHedgehog signaling pathway
Hedgehog signaling inhibitors
Targeted cancer therapy
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