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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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122-Selective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells..pdf (2.358Mb)
Date
2018-12-01
Author
Koyuncu, Ismail
Supuran, Claudiu T.
Durgun, Mustafa
Temiz, Ebru
Gonel, Ataman
KOÇYİĞİT, ABDÜRRAHİM
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Type
Article
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Abstract
Selective 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.
Subject
Carbonic anhydrase IX
sulphonamide
apoptosis
reactive oxygen species
anticancer agent
URI
https://hdl.handle.net/20.500.12645/1685
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052416/
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BEZMIALEM VAKIF UNIVERSITY

About us |Policies | Library | Contact us | Send Feedback | Sitemap | Admin

Bezmialem Vakıf Üniversitesi, Adnan Menderes Bulvarı Vatan Caddesi 34093 Fatih, İstanbul / TURKEY
Copyright © Bezmialem Vakıf Üniversitesi

Creative Commons Lisansı
Bezmialem Institutional Repository, Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

OpenAccess@BVU

Support by  UNIREPOS