Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness
Carbonic anhydrase IX (CA-IX) plays a pivotal role in regulation of pH in tumor milieu catalyzing carbonic acid formation by hydrating CO2. An acidification of tumor microenvironment contributes to tumor progression via multiple processes, including reduced cell-cell adhesion, increased migration an...
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ftunivsiena:oai:usiena-air.unisi.it:11365/1107102 2024-04-14T08:10:18+00:00 Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness Ciccone, Valerio Filippelli, Arianna Angeli, Andrea Supuran, Claudiu T. Morbidelli, Lucia Ciccone, Valerio Filippelli, Arianna Angeli, Andrea Supuran, Claudiu T. Morbidelli, Lucia 2020 ELETTRONICO http://hdl.handle.net/11365/1107102 https://doi.org/10.3390/ijms21082983 https://www.mdpi.com/1422-0067/21/8/2983 eng eng info:eu-repo/semantics/altIdentifier/pmid/32340282 info:eu-repo/semantics/altIdentifier/wos/WOS:000535565300325 volume:21 issue:8 numberofpages:17 journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES http://hdl.handle.net/11365/1107102 doi:10.3390/ijms21082983 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85083858889 https://www.mdpi.com/1422-0067/21/8/2983 info:eu-repo/semantics/openAccess Carbonic anhydrase IX cancer cell apoptosi epithelial-mesenchymal transition invasiveness info:eu-repo/semantics/article 2020 ftunivsiena https://doi.org/10.3390/ijms21082983 2024-03-21T16:12:31Z Carbonic anhydrase IX (CA-IX) plays a pivotal role in regulation of pH in tumor milieu catalyzing carbonic acid formation by hydrating CO2. An acidification of tumor microenvironment contributes to tumor progression via multiple processes, including reduced cell-cell adhesion, increased migration and matrix invasion. We aimed to assess whether the pharmacological inhibition of CA-IX could impair tumor cell proliferation and invasion. Tumor epithelial cells from breast (MDA-MB-231) and lung (A549) cancer were used to evaluate the cytotoxic eect of sulfonamide CA-IX inhibitors. Two CA-IX enzyme blockers were tested, SLC-0111 (at present in phase Ib clinical trial) and AA-06-05. In these cells, the drugs inhibited cell proliferation, migration and invasion through shifting of the mesenchymal phenotype toward an epithelial one and by impairing matrix metalloprotease-2 (MMP-2) activity. The antitumor activity was elicited via apoptosis pathway activation. An upregulation of p53 was observed, which in turn regulated the activation of caspase-3. Inhibition of proteolytic activity was accompanied by upregulation of the endogenous tissue inhibitor TIMP-2. Collectively, these data confirm the potential use of CA-IX inhibitors, and in particular SLC-0111 and AA-06-05, as agents to be further developed, alone or in combination with other conventional anticancer drugs. Article in Journal/Newspaper Carbonic acid Università degli Studi di Siena: USiena air International Journal of Molecular Sciences 21 8 2983 |
institution |
Open Polar |
collection |
Università degli Studi di Siena: USiena air |
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ftunivsiena |
language |
English |
topic |
Carbonic anhydrase IX cancer cell apoptosi epithelial-mesenchymal transition invasiveness |
spellingShingle |
Carbonic anhydrase IX cancer cell apoptosi epithelial-mesenchymal transition invasiveness Ciccone, Valerio Filippelli, Arianna Angeli, Andrea Supuran, Claudiu T. Morbidelli, Lucia Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness |
topic_facet |
Carbonic anhydrase IX cancer cell apoptosi epithelial-mesenchymal transition invasiveness |
description |
Carbonic anhydrase IX (CA-IX) plays a pivotal role in regulation of pH in tumor milieu catalyzing carbonic acid formation by hydrating CO2. An acidification of tumor microenvironment contributes to tumor progression via multiple processes, including reduced cell-cell adhesion, increased migration and matrix invasion. We aimed to assess whether the pharmacological inhibition of CA-IX could impair tumor cell proliferation and invasion. Tumor epithelial cells from breast (MDA-MB-231) and lung (A549) cancer were used to evaluate the cytotoxic eect of sulfonamide CA-IX inhibitors. Two CA-IX enzyme blockers were tested, SLC-0111 (at present in phase Ib clinical trial) and AA-06-05. In these cells, the drugs inhibited cell proliferation, migration and invasion through shifting of the mesenchymal phenotype toward an epithelial one and by impairing matrix metalloprotease-2 (MMP-2) activity. The antitumor activity was elicited via apoptosis pathway activation. An upregulation of p53 was observed, which in turn regulated the activation of caspase-3. Inhibition of proteolytic activity was accompanied by upregulation of the endogenous tissue inhibitor TIMP-2. Collectively, these data confirm the potential use of CA-IX inhibitors, and in particular SLC-0111 and AA-06-05, as agents to be further developed, alone or in combination with other conventional anticancer drugs. |
author2 |
Ciccone, Valerio Filippelli, Arianna Angeli, Andrea Supuran, Claudiu T. Morbidelli, Lucia |
format |
Article in Journal/Newspaper |
author |
Ciccone, Valerio Filippelli, Arianna Angeli, Andrea Supuran, Claudiu T. Morbidelli, Lucia |
author_facet |
Ciccone, Valerio Filippelli, Arianna Angeli, Andrea Supuran, Claudiu T. Morbidelli, Lucia |
author_sort |
Ciccone, Valerio |
title |
Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness |
title_short |
Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness |
title_full |
Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness |
title_fullStr |
Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness |
title_full_unstemmed |
Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness |
title_sort |
pharmacological inhibition of ca-ix impairs tumor cell proliferation, migration and invasiveness |
publishDate |
2020 |
url |
http://hdl.handle.net/11365/1107102 https://doi.org/10.3390/ijms21082983 https://www.mdpi.com/1422-0067/21/8/2983 |
genre |
Carbonic acid |
genre_facet |
Carbonic acid |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/32340282 info:eu-repo/semantics/altIdentifier/wos/WOS:000535565300325 volume:21 issue:8 numberofpages:17 journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES http://hdl.handle.net/11365/1107102 doi:10.3390/ijms21082983 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85083858889 https://www.mdpi.com/1422-0067/21/8/2983 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.3390/ijms21082983 |
container_title |
International Journal of Molecular Sciences |
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21 |
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8 |
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2983 |
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