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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Teixeira, Silvia A. [1, 2, 3, 4] ; Viapiano, Mariano S. [1, 3, 5] ; Andrade, Augusto F. [6] ; Nandhu, Mohan S. [1, 3, 5] ; Pezuk, Julia A. [7] ; Bidinotto, Lucas T. [8, 4, 9] ; Suazo, Veridiana K. [2] ; Neder, Luciano [10, 4] ; Carlotti, Carlos G. [11] ; Becker, Aline P. [12] ; Tone, Luiz Gonzaga [7, 2] ; Scrideli, Carlos A. [2]
Total Authors: 12
Affiliation:
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[1] Harvard Med Sch, Boston, MA 02115 - USA
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Paediat, Ribeirao Preto, SP - Brazil
[3] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 - USA
[4] Pio XII Fdn, Barretos Canc Hosp, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil
[5] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 - USA
[6] McGill Univ, Dept Human Genet, Montreal, PQ - Canada
[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil
[8] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Barretos, SP - Brazil
[9] UNESP Univ Estadual Paulista, Sch Med, Dept Pathol, Botucatu, SP - Brazil
[10] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Forens Med, Ribeirao Preto, SP - Brazil
[11] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Ribeirao Preto, SP - Brazil
[12] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 - USA
Total Affiliations: 12
Document type: Journal article
Source: Molecular Neurobiology; JUN 2021.
Web of Science Citations: 0
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: 11/07448-1 - Effects of inhibition of carbonic anhydrases 9 and 12 by E7070: implications on progression and therapeutics of glioblastomas
Grantee:Carlos Alberto Scrideli
Support type: Regular Research Grants
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 type: Scholarships abroad - Research Internship - Post-doctor
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 type: Scholarships in Brazil - Post-Doctorate