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
Ismail KoyuncuClaudiu T Supuran

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, caspase-8, 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 γ-H2AX and AO/EB dye, showed increased cleaved caspase-3, caspase-...Continue Reading

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Citations

Oct 27, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Ismail KoyuncuClaudiu T Supuran
Feb 28, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Ismail KoyuncuClaudiu T Supuran
Oct 27, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Dilek CanakciClaudiu T Supuran
Sep 21, 2019·Combinatorial Chemistry & High Throughput Screening·Mustafa CelikAtaman Gönel
Oct 28, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Jie ZhangQingyun Zeng
Aug 5, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Mikhail KrasavinClaudiu T Supuran
Jan 27, 2019·Expert Opinion on Drug Discovery·Emanuela Berrino, Claudiu T Supuran
Aug 14, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Giulia RotondiClaudiu T Supuran
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agnieszka GornowiczAnna Bielawska
Jul 3, 2021·International Journal of Molecular Sciences·Ebru TemizClaudiu T Supuran

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Methods Mentioned

BETA
flow cytometry
Assay
florescent microscopy
Fluorescence
protein assay
PCR
amino acid assay
ELISA

Software Mentioned

Cor
Li
Primer blast

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