Publication:
Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells

Simple item page
dc.contributor.authorTemiz, Ebru
dc.contributor.authorKoyuncu, Ismail
dc.contributor.authorDurgun, Mustafa
dc.contributor.authorCaglayan, Murat
dc.contributor.authorGonel, Ataman
dc.contributor.authorGüler, Eray Metin
dc.contributor.authorKOÇYİĞİT, ABDÜRRAHİM
dc.contributor.authorSupuran, Claudiu T.
dc.contributor.institutionauthorKOÇYİĞİT, ABDÜRRAHİM
dc.date.accessioned2021-06-17T20:59:06Z
dc.date.available2021-06-17T20:59:06Z
dc.date.issued2021-06-01T00:00:00Z
dc.description.abstractCarbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.
dc.description.sponsorshipTürkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tübitak )
dc.identifier.doi10.3390/ijms22116098
dc.identifier.pubmed34198834
dc.identifier.scopus85107271533
dc.identifier.urihttp://hdl.handle.net/20.500.12645/28988
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCAIX
dc.subjectanti-cancer agent
dc.subjectcell death
dc.subjectcervical cancer
dc.subjectsulphonamide
dc.titleInhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells
dc.typeArticle
dspace.entity.typePublication
local.avesis.id4f1138f7-a923-4f42-a2ab-e0fca6eea8de
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
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells.pdf
Size:
4.4 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Yayınlar - Eserler