Aнтитуморски потенцијал изонимесулида и његових деривата карборана
Antitumor potential of isonimesulide and its carborane derivatives
2023
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Authors:
Komazec, TeodoraUseini, Liridona
Mijatović, Sanja
Hey-Hawkins, Evamarie
Maksimović-Ivanić, Danijela
Contributors
Arsenijević, NebojšaDocument Type:
Conference object (Published version)
,
© 2023 by the Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine, Kragujevac, Serbia
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Show full item recordAbstract:
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as nimesulide have shown
antitumor effects against different types of tumor cell lines. The potential cytotoxic effect
of isonimesulide, a member of the nimesulide family, and its carborane derivatives
was determined against HT29, HCT116, MCF-7, A375, and A549 human cell lines. The
viability of all tested cell lines was dose-dependently decreased as shown by 3-(4,5-dimethythiazol-
2-yl)-2,5-diphenyltetrazolium bromide and crystal violet assays. The selectivity
of these compounds toward a tumor phenotype was demonstrated on MRC-5
and peritoneal exudate cells under identical experimental conditions. Flow cytometric
analysis revealed a significant reduction in the division potential of MCF-7 cells treated
with isonimesulide and two selected carborane derivatives (4a and 4b). Subsequently,
isonimesulide carborane derivatives induced strong apoptosis which was not mediated by
caspase activation. On the other hand, isonimesulide initiated caspase-mediated apoptosis
and reduced proliferation at a significantly lower rate than its carborane derivatives. In
further investigations, intensive apoptosis manifested with the irregular shape of nuclei,
and chromatin condensation was confirmed by propidium iodide (PI) staining of treated
MCF-7 cells using fluorescent microscopy. Finally, the inhibited production of reactive
oxygen and nitrogen species (ROS/RNS) was observed only in the case of 4b. The new features
of isonimesulide and its carborane derivatives are reflected in their strong antitumor
potential, which opens numerous possibilities for further research.
Keywords:
cancer; isonimesulide; carborane derivatives; antitumor potentialFunding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Arsenijević N, editor. Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine; 2023. p. 85-7.