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

Author(s):Show less -

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.

• Document type: Journal article
• Source: Molecular Neurobiology; v. N/A, p. 15-pg., 2021-06-03.

Abstract

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)

• FAPESP's process: 11/05957-6 - Effects of inhibition of carbonic anhydrases 9 and 12 by E7070 in vitro and in vivo: Implications on progression and therapeutics of glioblastomas
• Grantee: Silvia Aparecida Teixeira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/08899-5 - Effect of the silencing of CA12 and of the activation of NF-kB pathway TNFa in glioblastoma stem cell
• Grantee: Silvia Aparecida Teixeira
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 11/07448-1 - Effects of inhibition of carbonic anhydrases 9 and 12 by E7070: implications on progression and therapeutics of glioblastomas
• Grantee: Carlos Alberto Scrideli
• Support Opportunities: Regular Research Grants