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The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth

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Teixeira, Silvia A. ; Viapiano, Mariano S. ; Andrade, Augusto F. ; Nandhu, Mohan S. ; Pezuk, Julia A. ; Bidinotto, Lucas T. ; Suazo, Veridiana K. ; Neder, Luciano ; Carlotti, Carlos G. ; Becker, Aline P. ; Tone, Luiz Gonzaga ; Scrideli, Carlos A.
Número total de Autores: 12
Tipo de documento: Artigo Científico
Fonte: Molecular Neurobiology; v. N/A, p. 15-pg., 2021-06-03.
Resumo

Glioblastomas (GBMs), the most common and lethal primary brain tumor, show inherent infiltrative nature and high molecular heterogeneity that make complete surgical resection unfeasible and unresponsive to conventional adjuvant therapy. Due to their fast growth rate even under hypoxic and acidic conditions, GBM cells can conserve the intracellular pH at physiological range by overexpressing membrane-bound carbonic anhydrases (CAs). The synthetic sulfonamide E7070 is a potent inhibitor of CAs that harbors putative anticancer properties; however, this drug has still not been tested in GBMs. The present study aimed to evaluate the effects of E7070 on CA9 and CA12 enzymes in GBM cells as well as in the tumor cell growth, migration, invasion, and resistance to radiotherapy and chemotherapy. We found that E7070 treatment significantly reduced tumor cell growth and increased radio- and chemotherapy efficacy against GBM cells under hypoxia. Our data suggests that E7070 has therapeutic potential as a radio-chemo-sensitizing in drug-resistant GBMs, representing an attractive strategy to improve the adjuvant therapy. We showed that CA9 and CA12 represent potentially valuable therapeutic targets that should be further investigated as useful diagnostic and prognostic biomarkers for GBM tailored therapy. (AU)

Processo FAPESP: 11/05957-6 - Efeitos da inibição de anidrases carbônicas 9 e 12 pelo E7070 in vivo e in vitro: Implicações na progressão e na terapêutica dos glioblastomas
Beneficiário:Silvia Aparecida Teixeira
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 14/08899-5 - Efeito do silenciamento da CA12 e da ativação da do NF-kB, via TNFa, em células tronco de glioblastoma
Beneficiário:Silvia Aparecida Teixeira
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
Processo FAPESP: 11/07448-1 - Efeitos da inibição de anidrases carbônicas 9 e 12 pelo E7070: implicações na progressão e na terapêutica dos glioblastomas
Beneficiário:Carlos Alberto Scrideli
Modalidade de apoio: Auxílio à Pesquisa - Regular