Kaempferol induces apoptosis in glioblastoma cells through oxidative stress
| Autor: | Sourish Ghosh, Anindita Agarwal, Vivek Sharma, Ellora Sen, Manoj Kumar Mishra, Christy Joseph |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Small interfering RNA Apoptosis medicine.disease_cause Superoxide dismutase chemistry.chemical_compound Superoxide Dismutase-1 Thioredoxins Glioma Cell Line Tumor medicine Humans Kaempferols RNA Small Interfering Chemokine CCL2 chemistry.chemical_classification Membrane Potential Mitochondrial Reactive oxygen species biology Interleukin-6 Superoxide Dismutase Interleukin-8 medicine.disease Oxidants Molecular biology Mitochondria Oxidative Stress Oncology chemistry Proto-Oncogene Proteins c-bcl-2 Doxorubicin Caspases biology.protein Cancer research Thioredoxin Poly(ADP-ribose) Polymerases Kaempferol Glioblastoma Reactive Oxygen Species Oxidative stress |
| Zdroj: | Molecular cancer therapeutics. 6(9) |
| ISSN: | 1535-7163 |
| Popis: | Despite recent advances in understanding molecular mechanisms involved in glioblastoma progression, the prognosis of the most malignant brain tumor continues to be dismal. Because the flavonoid kaempferol is known to suppress growth of a number of human malignancies, we investigated the effect of kaempferol on human glioblastoma cells. Kaempferol induced apoptosis in glioma cells by elevating intracellular oxidative stress. Heightened oxidative stress was characterized by an increased generation of reactive oxygen species (ROS) accompanied by a decrease in oxidant-scavenging agents such as superoxide dismutase (SOD-1) and thioredoxin (TRX-1). Knockdown of SOD-1 and TRX-1 expression by small interfering RNA (siRNA) increased ROS generation and sensitivity of glioma cells to kaempferol-induced apoptosis. Signs of apoptosis included decreased expression of Bcl-2 and altered mitochondrial membrane potential with elevated active caspase-3 and cleaved poly(ADP-ribose) polymerase expression. Plasma membrane potential and membrane fluidity were altered in kaempferol-treated cells. Kaempferol suppressed the expression of proinflammatory cytokine interleukin-6 and chemokines interleukin-8, monocyte chemoattractant protein-1, and regulated on activation, normal T-cell expressed and secreted. Kaempferol inhibited glioma cell migration in a ROS-dependent manner. Importantly, kaempferol potentiated the toxic effect of chemotherapeutic agent doxorubicin by amplifying ROS toxicity and decreasing the efflux of doxorubicin. Because the toxic effect of both kaempferol and doxorubicin was amplified when used in combination, this study raises the possibility of combinatorial therapy whose basis constitutes enhancing redox perturbation as a strategy to kill glioma cells. [Mol Cancer Ther 2007;6(9):2544–53] |
| Databáze: | OpenAIRE |
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