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Selective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells

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dc.contributor.authorKoyuncu, Ismail
dc.contributor.authorGonel, Ataman
dc.contributor.authorKOÇYİĞİT, ABDÜRRAHİM
dc.contributor.authorTemiz, Ebru
dc.contributor.authorDurgun, Mustafa
dc.contributor.authorSupuran, Claudiu T.
dc.contributor.institutionauthorKOÇYİĞİT, ABDÜRRAHİM
dc.date.accessioned2019-10-05T13:14:14Z
dc.date.available2019-10-05T13:14:14Z
dc.date.issued2018-12-01
dc.description.abstractSelective inhibition with sulphonamides of carbonic anhydrase (CA) IX reduces cell proliferation and induces apoptosis in human cancer cells. The effect on CA IX expression of seven previously synthesised sulphonamide inhibitors, with high affinity for CA IX, as well as their effect on the proliferation/apoptosis of cancer/normal cell lines was investigated. Two normal and three human cancer cell lines were used. Treatment resulted in dose- and time-dependent inhibition of the growth of various cancer cell lines. One compound showed remarkably high toxicity towards CA IX-positive HeLa cells. The mechanisms of apoptosis induction were determined with Annexin-V and AO/EB staining, cleaved caspases (caspase-3, caspase8, caspase-9) and cleaved PARP activation, reactive oxygen species production (ROS), mitochondrial membrane potential (MMP), intracellular pH (pHi), extracellular pH (pHe), lactate level and cell cycle analysis. The autophagy induction mechanisms were also investigated. The modulation of apoptotic and autophagic genes (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin and LC3) was measured using real time PCR. The positive staining using c-H2AX and AO/EB dye, showed increased cleaved caspase-3, caspase-8, caspase-9, increased ROS production, MMP and enhanced mRNA expression of apoptotic genes, suggesting that anticancer effects are also exerted through its apoptosis-inducing properties. Our results show that such sulphonamides might have the potential as new leads for detailed investigations against CA IX-positive cervical cancers.en
dc.description.sponsorshipTürkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tübitak )
dc.identifier
dc.identifier.citationKoyuncu I., Gonel A., KOÇYİĞİT A., Temiz E., Durgun M., Supuran C. T. , -Selective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells-, Journal of enzyme inhibition and medicinal chemistry, cilt.33, ss.1137-1149, 2018
dc.identifier.doi10.1080/14756366.2018.1481403
dc.identifier.pubmed30001631
dc.identifier.scopus85050193069
dc.identifier.urihttps://hdl.handle.net/20.500.12645/1685
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052416/
dc.identifier.wosWOS:000438640300001
dc.language.isoen
dc.rightsinfo:eu-repo/semantics/openAccessen
dc.subjectCarbonic anhydrase IX
dc.subjectsulphonamide
dc.subjectapoptosis
dc.subjectreactive oxygen species
dc.subjectanticancer agent
dc.titleSelective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells
dc.typeArticle
dspace.entity.typePublication
local.article.journalnameBEZMIALEM SCIENCE
local.avesis.id28224f82-b558-4efe-ba4a-e2f370c1233d
local.avesis.response1555
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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