Modulation of tumor necrosis factor-mediated cell death by fullerenes
2008
Authors:
Harhaji-Trajković, LjubicaIsaković, Aleksandra
Vučićević, Ljubica
Janjetović, Kristina
Misirkić Marjanović, Maja
Marković, Zoran
Todorović-Marković, Biljana
Nikolić, Nadežda
Vranješ-Đurić, Sanja
Nikolić, Zoran
Trajković, Vladimir
Document Type:
Article (Published version)
,
© 2007 Springer Science + Business Media, LLC
Metadata
Show full item recordAbstract:
Purpose. The fullerene (C60/C70 mixture—C60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC60/70) and polyhydroxylated C60/70 [C60/70(OH)n] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF).
Materials and Methods. TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal
violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes.
Results. THF/nC60/70 augmented, while C60/70(OH)n reduced the cytotoxicity of TNF. The numbers of
cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing
enzymes of caspase family, were respectively increased or reduced by THF/nC60/70 or C60/70(OH)n. The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each
partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and
mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC60/70 or C60/70(OH)n potentiated
or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization.
Conclusion. The ability of different fullerene preparations to modulate TNF-induced oxidative stress
and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention
of TNF-dependent tissue damage
Keywords:
apoptosis; fullerene; necrosis; oxidative stress; tumor necrosis factorSource:
Pharmaceutical Research, 2008, 25, 6, 1365-1376Funding / projects:
- Citotoksični, citoprotektivni i imunomodulatorni efekti nanočestica (RS-MESTD-MPN2006-2010-145073)
DOI: 10.1007/s11095-007-9486-y
ISSN: 0724-8741
PubMed: 17999162