Abstract | BACKGROUND:
Glioblastoma multiforme (GBM) is the most aggressive of the primary brain tumors, with a grim prognosis despite intensive treatment. In the past decades, progress in research has not significantly increased overall survival rate. METHODS: RESULTS: Cas III-ia significantly inhibited cell proliferation, inducing autophagy and apoptosis, which correlated with the formation of autophagic vacuoles, overexpression of LC3, Beclin 1, Atg 7, Bax and Bid proteins. A decrease was detected in the mitochondrial membrane potential and in the activity of caspase 3 and 8, together with the generation of intracellular reactive oxygen species (ROS) and increased activity of c-jun NH(2)-terminal kinase (JNK). The presence of 3-methyladenine (as selective autophagy inhibitor) increased the antineoplastic effect of Cas III-ia, while Z-VAD-FMK only showed partial protection from the antineoplastic effect induced by Cas III-ia, and ROS antioxidants ( N-acetylcysteine) decreased apoptosis, autophagy and JNK activity. Moreover, the JNK -specific inhibitor SP600125 prevented Cas III-ia-induced cell death. CONCLUSIONS: Our data suggest that Cas III-ia induces cell death by autophagy and apoptosis, in part due to the activation of ROS -dependent JNK signaling. These findings support further studies of Cas III-ia as candidate for treatment of human malignant glioma.
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Authors | Cristina Trejo-Solís, Dolores Jimenez-Farfan, Sara Rodriguez-Enriquez, Francisca Fernandez-Valverde, Arturo Cruz-Salgado, Lena Ruiz-Azuara, Julio Sotelo |
Journal | BMC cancer
(BMC Cancer)
Vol. 12
Pg. 156
(Apr 27 2012)
ISSN: 1471-2407 [Electronic] England |
PMID | 22540380
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- (4,4-dimethyl-2,2-bipyridine)(acetylacetonate)copper(II)
- Antineoplastic Agents
- Organometallic Compounds
- Reactive Oxygen Species
- Copper
- Catalase
- Superoxide Dismutase
- JNK Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Autophagy
(drug effects)
- Catalase
(metabolism)
- Cell Line, Tumor
- Copper
- Enzyme Activation
(drug effects)
- Glioma
(metabolism)
- Humans
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- Organometallic Compounds
(pharmacology)
- Rats
- Reactive Oxygen Species
(metabolism)
- Superoxide Dismutase
(metabolism)
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