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Indisulam Reduces Viability and Regulates Apoptotic Gene Expression in Pediatric High-Grade Glioma Cells.
Monção, Caio C D; Scrideli, Carlos A; Andrade, Augusto F; Viapiano, Mariano S; Carlotti, Carlos G; Moreno, Daniel Antunes; Baroni, Mirella; Tone, Luiz G; Teixeira, Silvia A.
Afiliación
  • Monção CCD; Department of Paediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil.
  • Scrideli CA; Department of Paediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil.
  • Andrade AF; Department of Paediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil.
  • Viapiano MS; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
  • Carlotti CG; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Moreno DA; Departments of Neurosurgery and Neuroscience & Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
  • Baroni M; Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil.
  • Tone LG; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, São Paulo, Brazil.
  • Teixeira SA; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, São Paulo, Brazil.
Biomedicines ; 11(1)2022 Dec 27.
Article en En | MEDLINE | ID: mdl-36672576
Pediatric high-grade glioma (pHGG) is one of the most aggressive brain tumors. Treatment includes surgery, radiotherapy, chemotherapy, or combination therapy in children older than 3−5 years of age. These devastating tumors are influenced by the hypoxic microenvironment that coordinatively increases the expression of carbonic anhydrases (CA9 and CA12) that are involved in pH regulation, metabolism, cell invasion, and resistance to therapy. The synthetic sulphonamide Indisulam is a potent inhibitor of CAs. The aim of this study was to evaluate the effects of Indisulam on CA9 and CA12 enzymes in pHGG cell lines. Our results indicated that, under hypoxia, the gene and protein expression of CA9 and CA12 are increased in pHGG cells. The functional effects of Indisulam on cell proliferation, clonogenic capacity, and apoptosis were measured in vitro. CA9 and CA12 gene and protein expression were analyzed by RT-PCR and western blot. The treatment with Indisulam significantly reduced cell proliferation (dose-time-dependent) and clonogenic capacity (p < 0.05) and potentiated the effect of apoptosis (p < 0.01). Indisulam promoted an imbalance in the anti-apoptotic BCL2 and pro-apoptotic BAX protein expression. Our results demonstrate that Indisulam contributes to apoptosis via imbalance of apoptotic proteins (BAX/BCL2) and suggests a potential to overcome chemotherapy resistance caused by the regulation these proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomedicines Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomedicines Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza