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Intracellular pH-mediated induction of apoptosis in HeLa cells by a sulfonamide carbonic anhydrase inhibitor

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dc.contributor.authorKoyuncu, Ismail
dc.contributor.authorTemiz, Ebru
dc.contributor.authorDurgun, Mustafa
dc.contributor.authorKOÇYİĞİT, ABDÜRRAHİM
dc.contributor.authorYuksekdag, Ozgur
dc.contributor.authorSupuran, Claudiu T.
dc.contributor.institutionauthorKOÇYİĞİT, ABDÜRRAHİM
dc.date.accessioned2022-01-13T21:00:30Z
dc.date.available2022-01-13T21:00:30Z
dc.date.issued2022-03-15T00:00:00Z
dc.description.abstract© 2021Carbonic anhydrase IX (CAIX) is a hypoxia-associated transmembrane protein that is critical in the survival of cells. Because CAIX has a key role in pH regulation, its therapeutic effects have been heavily studied by different research laboratories. This study aims to investigate how a synthetic CAIX inhibitor triggers apoptosis in a cancer cell line, HeLa. In this regard, we investigated the effects of the compound I, synthesized as a CAIX inhibitor, on the survival of cancer cells. The compound I inhibited the proliferation of the CAIX+ HeLa cells, kept the cells in G0/G1 phase (74.7%) and altered the cells morphologies (AO/EtBr staining) and the nuclear structure (γ-H2AX staining). CAIX inhibition triggered apoptosis in HeLa cells with a rate of 47.4%. According to the expression of mediator genes (CASP-3, -8, -9, BAX, BCL-2, BECLIN, LC3), the both death pathways were activated in HeLa cells with the inhibition of CAIX with the compound I. The compound I was also determined to affect the genes and proteins that have a critical role in the regulation of apoptotic pathways (pro casp-3, cleaved casp-3, -8, -9, cleaved PARP and CAIX). Furthermore, CAIX inhibition caused changes in pH balance, disruption in organelle integrity of mitochondria, and increase intracellular reactive oxygen level of HeLa cells. Taken together, our findings suggest that CAIX inhibition has a potential in cancer treatment, and the compound I, a CAIX inhibitor, could be a promising therapeutic strategy in the treatment of aggressive tumours.
dc.identifier.citationKoyuncu I., Temiz E., Durgun M., KOÇYİĞİT A., Yuksekdag O., Supuran C. T. , -Intracellular pH-mediated induction of apoptosis in HeLa cells by a sulfonamide carbonic anhydrase inhibitor-, International Journal of Biological Macromolecules, cilt.201, ss.37-46, 2022
dc.identifier.doi10.1016/j.ijbiomac.2021.12.190
dc.identifier.pubmed34999037
dc.identifier.scopus85122281424
dc.identifier.urihttp://hdl.handle.net/20.500.12645/30186
dc.titleIntracellular pH-mediated induction of apoptosis in HeLa cells by a sulfonamide carbonic anhydrase inhibitor
dc.typeArticle
dspace.entity.typePublication
local.avesis.idebd05f22-6292-4563-8a23-675b95e6cb57
local.publication.goal03 - Sağlık ve Kaliteli Yaşam
local.publication.isinternational1
relation.isAuthorOfPublication75babbd2-f46b-4121-aa00-54d883a6f907
relation.isAuthorOfPublication.latestForDiscovery75babbd2-f46b-4121-aa00-54d883a6f907
relation.isGoalOfPublication9c198c48-b603-4e2f-8366-04edcfc1224c
relation.isGoalOfPublication.latestForDiscovery9c198c48-b603-4e2f-8366-04edcfc1224c
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