The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1007/s12035-021-02437-3 http://hdl.handle.net/11449/207952 |
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. |
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The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor GrowthCarbonic anhydraseCell metabolismHypoxic microenvironmentPDX modelPH regulationGlioblastomas (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.Department of Paediatrics Ribeirão Preto Medical School University of São PauloDepartment of Neurosurgery Brigham and Women’s Hospital and Harvard Medical SchoolMolecular Oncology Research Center Barretos Cancer Hospital Pio XII Foundation, Rua Antenor Duarte Villela, 1331Department of Neuroscience and Physiology SUNY Upstate Medical UniversityDepartment of Human Genetics McGill UniversityDepartment of Genetics Ribeirão Preto Medical School University of São PauloDepartment of Pathology School of Medicine UNESP – Univ. Estadual PaulistaBarretos School of Health Sciences Dr. Paulo Prata – FACISBDepartment of Pathology and Forensic Medicine Ribeirão Preto Medical School University of São PauloDepartment of Surgery and Anatomy Ribeirão Preto Medical School University of São PauloDepartment of Radiation Oncology The Ohio State UniversityDepartment of Pathology School of Medicine UNESP – Univ. Estadual PaulistaUniversidade de São Paulo (USP)Brigham and Women’s Hospital and Harvard Medical SchoolPio XII FoundationSUNY Upstate Medical UniversityMcGill UniversityUniversidade Estadual Paulista (Unesp)Dr. Paulo Prata – FACISBThe Ohio State UniversityTeixeira, Silvia A.Viapiano, Mariano S.Andrade, Augusto F.Nandhu, Mohan S.Pezuk, Julia A.Bidinotto, Lucas T. [UNESP]Suazo, Veridiana K.Neder, LucianoCarlotti, Carlos G.Becker, Aline P.Tone, Luiz GonzagaScrideli, Carlos A.2021-06-25T11:03:47Z2021-06-25T11:03:47Z2021-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1007/s12035-021-02437-3Molecular Neurobiology.1559-11820893-7648http://hdl.handle.net/11449/20795210.1007/s12035-021-02437-32-s2.0-85107391610Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMolecular Neurobiologyinfo:eu-repo/semantics/openAccess2021-10-23T17:52:07Zoai:repositorio.unesp.br:11449/207952Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T17:52:07Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
title |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
spellingShingle |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth Teixeira, Silvia A. Carbonic anhydrase Cell metabolism Hypoxic microenvironment PDX model PH regulation |
title_short |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
title_full |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
title_fullStr |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
title_full_unstemmed |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
title_sort |
The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
author |
Teixeira, Silvia A. |
author_facet |
Teixeira, Silvia A. Viapiano, Mariano S. Andrade, Augusto F. Nandhu, Mohan S. Pezuk, Julia A. Bidinotto, Lucas T. [UNESP] Suazo, Veridiana K. Neder, Luciano Carlotti, Carlos G. Becker, Aline P. Tone, Luiz Gonzaga Scrideli, Carlos A. |
author_role |
author |
author2 |
Viapiano, Mariano S. Andrade, Augusto F. Nandhu, Mohan S. Pezuk, Julia A. Bidinotto, Lucas T. [UNESP] Suazo, Veridiana K. Neder, Luciano Carlotti, Carlos G. Becker, Aline P. Tone, Luiz Gonzaga Scrideli, Carlos A. |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Brigham and Women’s Hospital and Harvard Medical School Pio XII Foundation SUNY Upstate Medical University McGill University Universidade Estadual Paulista (Unesp) Dr. Paulo Prata – FACISB The Ohio State University |
dc.contributor.author.fl_str_mv |
Teixeira, Silvia A. Viapiano, Mariano S. Andrade, Augusto F. Nandhu, Mohan S. Pezuk, Julia A. Bidinotto, Lucas T. [UNESP] Suazo, Veridiana K. Neder, Luciano Carlotti, Carlos G. Becker, Aline P. Tone, Luiz Gonzaga Scrideli, Carlos A. |
dc.subject.por.fl_str_mv |
Carbonic anhydrase Cell metabolism Hypoxic microenvironment PDX model PH regulation |
topic |
Carbonic anhydrase Cell metabolism Hypoxic microenvironment PDX model PH regulation |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T11:03:47Z 2021-06-25T11:03:47Z 2021-01-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1007/s12035-021-02437-3 Molecular Neurobiology. 1559-1182 0893-7648 http://hdl.handle.net/11449/207952 10.1007/s12035-021-02437-3 2-s2.0-85107391610 |
url |
http://dx.doi.org/10.1007/s12035-021-02437-3 http://hdl.handle.net/11449/207952 |
identifier_str_mv |
Molecular Neurobiology. 1559-1182 0893-7648 10.1007/s12035-021-02437-3 2-s2.0-85107391610 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecular Neurobiology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799964921315721216 |