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Modulation of tumor necrosis factor-mediated cell death by fullerenes

Нема приказа
Аутори
Harhaji, Ljubica M.
Isaković, Aleksandra J.
Vucicevic, Ljubica
Janjetović, Kristina D.
Misirkic, Maja
Marković, Zoran M.
Todorović-Marković, Biljana
Nikolić, Nadežda S.
Vranješ-Đurić, Sanja
Nikolić, Zoran M.
Trajković, Vladimir S.
Чланак у часопису
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Приказ свих података о документу
Апстракт
Purpose. The fullerene (C-60/C-70 mixture-C-60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC(60/70)) and polyhydroxylated C-60/70 [C-60/70(OH)(n)] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNT). 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/nC(60/70) augmented, while C-60/70(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/nC(60/70) or C-60/70(OH)(n). The antioxidant N-acetylcysteine and mitochondrial per...meability 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/nC(60/70) or C-60/70(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.

Кључне речи:
apoptosis / fullerene / necrosis / oxidative stress / tumor necrosis factor
Извор:
Pharmaceutical Research, 2008, 25, 6, 1365-1376

DOI: 10.1007/s11095-007-9486-y

ISSN: 0724-8741 (print)

PubMed: 17999162

WoS: 000255753900012

Scopus: 2-s2.0-43149126321
[ Google Scholar ]
URI
http://vinar.vin.bg.ac.rs/123456789/3445
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