The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth
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 con...
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| Veröffentlicht in: | Molecular neurobiology 2021-09, Vol.58 (9), p.4520-4534 |
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| creator | 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. |
| 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. |
| doi_str_mv | 10.1007/s12035-021-02437-3 |
| format | Article |
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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. 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The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-5c3e00e620afe85325bdb2c7b96867685bfe4e354b287f84100e90d8861e49b3</citedby><cites>FETCH-LOGICAL-c375t-5c3e00e620afe85325bdb2c7b96867685bfe4e354b287f84100e90d8861e49b3</cites><orcidid>0000-0002-2462-8535</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-021-02437-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-021-02437-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34085182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teixeira, Silvia A.</creatorcontrib><creatorcontrib>Viapiano, Mariano S.</creatorcontrib><creatorcontrib>Andrade, Augusto F.</creatorcontrib><creatorcontrib>Nandhu, Mohan S.</creatorcontrib><creatorcontrib>Pezuk, Julia A.</creatorcontrib><creatorcontrib>Bidinotto, Lucas T.</creatorcontrib><creatorcontrib>Suazo, Veridiana K.</creatorcontrib><creatorcontrib>Neder, Luciano</creatorcontrib><creatorcontrib>Carlotti, Carlos G.</creatorcontrib><creatorcontrib>Becker, Aline P.</creatorcontrib><creatorcontrib>Tone, Luiz Gonzaga</creatorcontrib><creatorcontrib>Scrideli, Carlos A.</creatorcontrib><title>The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><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.</description><subject>Apoptosis - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain tumors</subject><subject>Carbonic Anhydrase Inhibitors - pharmacology</subject><subject>Carbonic Anhydrase Inhibitors - therapeutic use</subject><subject>Carbonic anhydrases</subject><subject>Cell Biology</subject><subject>Cell Cycle - drug effects</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotherapy</subject><subject>Drug resistance</subject><subject>Glioblastoma</subject><subject>Glioblastoma - drug therapy</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma cells</subject><subject>Growth rate</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Radiation therapy</subject><subject>Sulfonamides</subject><subject>Sulfonamides - pharmacology</subject><subject>Therapeutic targets</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUFr3DAQhUVpaTZJ_0APRdBLL25HkmXJx2DSTSAQSPYuJHtcK9jWVrJptr--ajZtoYccBsHoe2-GeYS8Z_CZAagviXEQsgDOcpVCFeIV2TAp64IxzV-TDehaFKoq9Qk5TekBgHMG6i05ESVomZkNedwNSBsbXZh9Sy_m4dBFm5Bez4N3fgmRXipQQO9xTn7xPzHR7eiDG21awmRpg-OY6BLone18KKidO9oMOIVlwGj3h6fGHXZrm5W7dcqG2xh-LMM5edPbMeG75_eM7L5e7pqr4uZ2e91c3BStUHIpZCsQACsOtkctBZeuc7xVrq50pSotXY8lClk6rlWvy3wYrKHTumJY1k6ckU9H230M31dMi5l8avPSdsawJsOlyAeCsoaMfvwPfQhrnPNymVJa8lozlSl-pNoYUorYm330k40Hw8D8jsUcYzE5FvMUixFZ9OHZenUTdn8lf3LIgDgCKX_N3zD-m_2C7S-Hh5a2</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Teixeira, Silvia A.</creator><creator>Viapiano, Mariano S.</creator><creator>Andrade, Augusto F.</creator><creator>Nandhu, Mohan S.</creator><creator>Pezuk, Julia A.</creator><creator>Bidinotto, Lucas T.</creator><creator>Suazo, Veridiana K.</creator><creator>Neder, Luciano</creator><creator>Carlotti, Carlos G.</creator><creator>Becker, Aline P.</creator><creator>Tone, Luiz Gonzaga</creator><creator>Scrideli, Carlos A.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2462-8535</orcidid></search><sort><creationdate>20210901</creationdate><title>The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-5c3e00e620afe85325bdb2c7b96867685bfe4e354b287f84100e90d8861e49b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Apoptosis - 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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. 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| subjects | Apoptosis - drug effects Biomedical and Life Sciences Biomedicine Brain cancer Brain Neoplasms - drug therapy Brain Neoplasms - pathology Brain tumors Carbonic Anhydrase Inhibitors - pharmacology Carbonic Anhydrase Inhibitors - therapeutic use Carbonic anhydrases Cell Biology Cell Cycle - drug effects Cell growth Cell Line, Tumor Cell migration Cell Movement - drug effects Cell Proliferation - drug effects Chemotherapy Drug resistance Glioblastoma Glioblastoma - drug therapy Glioblastoma - pathology Glioblastoma cells Growth rate Humans Hypoxia Neurobiology Neurology Neurosciences Radiation therapy Sulfonamides Sulfonamides - pharmacology Therapeutic targets |
| title | The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth |
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