Synergistic antiglioma action of hyperthermia and nitric oxide
2008
Authors:
Janjetović, KristinaMisirkić Marjanović, Maja
Vučićević, Ljubica
Harhaji-Trajković, Ljubica
Trajković, Vladimir
Document Type:
Article (Published version)
,
© 2008 Elsevier B.V.
Metadata
Show full item recordAbstract:
To explore combined antiglioma effect of nitric oxide (NO) and hyperthermia, the rat C6 and human U251 glioma cells were exposed to NO-releasing agents sodium nitroprusside(SNP), S-nitrosoglutathione or PAPA-NONOate, followed by hyperthermia (1 h, 43 degrees C). While each treatment alone showed only moderate efficiency, a synergistic cytotoxicity of NO donors and hyperthermia was clearly demonstrated by crystal violet and MTT cytotoxicity assays. The flow cytometric analysis with the appropriate reporter fluorochromes confirmed that hyperthermia and SNP cooperated in inducing oxidative stress, mitochondrial depolarization, caspase activation and DNA fragmentation, leading to both necrotic and caspase-dependent apoptotic cell death. The acridine orange staining of intracellular acidic compartments revealed that SNP completely blocked hyperthermia-induced autophagy, while the inhibition of autophagy by 3-methyl adenine mimicked SNP-triggered oxidative stress, caspase activation and cell death in hyperthermia-exposed cells. Therefore, the synergistic cytotoxicity of SNP and hyperthermia could result from NO-mediated suppression of protective autophagic response in glioma cells.
Keywords:
Hyperthermia; Nitric oxide; Glioma; Oxidative stress; Mitochondrial depolarization apoptosis; Necrosis; AutophagySource:
European Journal of Pharmacology, 2008, 583, 1, 1-10Funding / projects:
- Citotoksični, citoprotektivni i imunomodulatorni efekti nanočestica (RS-MESTD-MPN2006-2010-145073)
DOI: 10.1016/j.ejphar.2007.12.028
ISSN: 0014-2999
PubMed: 18262519