Modulation of Tumor Necrosis Factor-mediated Cell Death by Fullerenes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-06

AUTHORS

Ljubica Harhaji, Aleksandra Isakovic, Ljubica Vucicevic, Kristina Janjetovic, Maja Misirkic, Zoran Markovic, Biljana Todorovic-Markovic, Nadezda Nikolic, Sanja Vranjes-Djuric, Zoran Nikolic, Vladimir Trajkovic

ABSTRACT

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. More... »

PAGES

1365-1376

References to SciGraph publications

  • 1997-12. Apoptosis: A New Pharmacodynamic Endpoint in PHARMACEUTICAL RESEARCH
  • 1988-09. Resistance of tumor cells to tumor necrosis factor in JOURNAL OF CLINICAL IMMUNOLOGY
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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s11095-007-9486-y

    DOI

    http://dx.doi.org/10.1007/s11095-007-9486-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039391913

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17999162


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