Assessment of the antiproliferative and apoptotic roles of sulfonamide carbonic anhydrase IX inhibitors in HeLa cancer cell line.
Antigens, Neoplasm
/ genetics
Antineoplastic Combined Chemotherapy Protocols
/ chemistry
Apoptosis
/ drug effects
Carbonic Anhydrase IX
/ antagonists & inhibitors
Carbonic Anhydrase Inhibitors
/ chemistry
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
DNA Damage
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Hydrogen-Ion Concentration
Membrane Potential, Mitochondrial
/ drug effects
Molecular Structure
Reactive Oxygen Species
/ analysis
Structure-Activity Relationship
Carbonic anhydrase IX
HeLa cell
anticancer agent
apoptosis
sulfonamide
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
27
10
2018
pubmed:
27
10
2018
medline:
10
11
2018
Statut:
ppublish
Résumé
Carbonic anhydrase IX (CA IX) has recently been validated as an antitumor/antimetastatic drug target. In this study, we examined the underlying molecular mechanisms and the anticancer activity of sulfonamide CA IX inhibitors against cervical cancer cell lines. The effects of several sulfonamides on HeLa, MDA-MB-231, HT-29 cancer cell lines, and normal cell lines (HEK-293, PNT-1A) viability were determined. The compounds showed high cytotoxic and apoptotic activities, mainly against HeLa cells overexpressing CA IX. We were also examined for intracellular reactive oxygen species (ROS) production; intra-/extracellular pH changes, for inhibition of cell proliferation, cellular mitochondrial membrane potential change and for the detection of caspase 3, 8, 9, and CA IX protein levels. Of the investigated sulfonamides, one compound was found to possess high cytotoxic and anti-proliferative effects in HeLa cells. The cytotoxic effect occurred via apoptosis, being accompanied by a return of pHe/pHi towards normal values as for other CA IX inhibitors investigated earlier.
Identifiants
pubmed: 30362386
doi: 10.1080/14756366.2018.1524380
pmc: PMC6211230
doi:
Substances chimiques
Antigens, Neoplasm
0
Carbonic Anhydrase Inhibitors
0
Reactive Oxygen Species
0
CA9 protein, human
EC 4.2.1.1
Carbonic Anhydrase IX
EC 4.2.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-86Références
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