Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line
Carbonic anhydrase IX (CA IX) has recently been validated as an antitumor/antimetastatic drug target. In this study, we examined the underlying molecular mechanisms and the anticancer activity of sulfonamide CA IX inhibitors against cervical cancer cell lines. The effects of several sulfonamides on...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1524380 |
| _version_ | 1818533379114532864 |
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| author | Ismail Koyuncu Ataman Gonel Mustafa Durgun Abdurrahim Kocyigit Ozgur Yuksekdag Claudiu T. Supuran |
| author_facet | Ismail Koyuncu Ataman Gonel Mustafa Durgun Abdurrahim Kocyigit Ozgur Yuksekdag Claudiu T. Supuran |
| author_sort | Ismail Koyuncu |
| collection | DOAJ |
| description | Carbonic anhydrase IX (CA IX) has recently been validated as an antitumor/antimetastatic drug target. In this study, we examined the underlying molecular mechanisms and the anticancer activity of sulfonamide CA IX inhibitors against cervical cancer cell lines. The effects of several sulfonamides on HeLa, MDA-MB-231, HT-29 cancer cell lines, and normal cell lines (HEK-293, PNT-1A) viability were determined. The compounds showed high cytotoxic and apoptotic activities, mainly against HeLa cells overexpressing CA IX. We were also examined for intracellular reactive oxygen species (ROS) production; intra-/extracellular pH changes, for inhibition of cell proliferation, cellular mitochondrial membrane potential change and for the detection of caspase 3, 8, 9, and CA IX protein levels. Of the investigated sulfonamides, one compound was found to possess high cytotoxic and anti-proliferative effects in HeLa cells. The cytotoxic effect occurred via apoptosis, being accompanied by a return of pHe/pHi towards normal values as for other CA IX inhibitors investigated earlier. |
| first_indexed | 2024-12-11T17:57:54Z |
| format | Article |
| id | doaj.art-352e4bbed237412bbb7b18e3f4d9dcf8 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-11T17:57:54Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-352e4bbed237412bbb7b18e3f4d9dcf82022-12-22T00:55:59ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-01341758610.1080/14756366.2018.15243801524380Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell lineIsmail Koyuncu0Ataman Gonel1Mustafa Durgun2Abdurrahim Kocyigit3Ozgur Yuksekdag4Claudiu T. Supuran5Harran UniversityHarran UniversityHarran UniversityBezmialem Vakif UniversityHarran UniversityUniversità degli Studi di FirenzeCarbonic anhydrase IX (CA IX) has recently been validated as an antitumor/antimetastatic drug target. In this study, we examined the underlying molecular mechanisms and the anticancer activity of sulfonamide CA IX inhibitors against cervical cancer cell lines. The effects of several sulfonamides on HeLa, MDA-MB-231, HT-29 cancer cell lines, and normal cell lines (HEK-293, PNT-1A) viability were determined. The compounds showed high cytotoxic and apoptotic activities, mainly against HeLa cells overexpressing CA IX. We were also examined for intracellular reactive oxygen species (ROS) production; intra-/extracellular pH changes, for inhibition of cell proliferation, cellular mitochondrial membrane potential change and for the detection of caspase 3, 8, 9, and CA IX protein levels. Of the investigated sulfonamides, one compound was found to possess high cytotoxic and anti-proliferative effects in HeLa cells. The cytotoxic effect occurred via apoptosis, being accompanied by a return of pHe/pHi towards normal values as for other CA IX inhibitors investigated earlier.http://dx.doi.org/10.1080/14756366.2018.1524380carbonic anhydrase ixsulfonamideapoptosishela cellanticancer agent |
| spellingShingle | Ismail Koyuncu Ataman Gonel Mustafa Durgun Abdurrahim Kocyigit Ozgur Yuksekdag Claudiu T. Supuran Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line Journal of Enzyme Inhibition and Medicinal Chemistry carbonic anhydrase ix sulfonamide apoptosis hela cell anticancer agent |
| title | Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line |
| title_full | Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line |
| title_fullStr | Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line |
| title_full_unstemmed | Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line |
| title_short | Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line |
| title_sort | assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase ix inhibitors in hela cancer cell line |
| topic | carbonic anhydrase ix sulfonamide apoptosis hela cell anticancer agent |
| url | http://dx.doi.org/10.1080/14756366.2018.1524380 |
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