Kaempferol induces apoptosis in glioblastoma cells through oxidative stress

摘要: Despite recent advances in understanding molecular mechanisms involved glioblastoma progression, the prognosis of most malignant brain tumor continues to be dismal. Because flavonoid kaempferol is known suppress growth a number human malignancies, we investigated effect on cells. Kaempferol induced apoptosis glioma cells by elevating intracellular oxidative stress. Heightened stress was characterized an increased generation reactive oxygen species (ROS) accompanied decrease oxidant-scavenging agents such as superoxide dismutase (SOD-1) and thioredoxin (TRX-1). Knockdown SOD-1 TRX-1 expression small interfering RNA (siRNA) ROS sensitivity kaempferol-induced apoptosis. Signs included decreased Bcl-2 altered mitochondrial membrane potential with elevated active caspase-3 cleaved poly(ADP-ribose) polymerase expression. Plasma fluidity were kaempferol-treated suppressed proinflammatory cytokine interleukin-6 chemokines interleukin-8, monocyte chemoattractant protein-1, regulated activation, normal T-cell expressed secreted. inhibited cell migration ROS-dependent manner. Importantly, potentiated toxic chemotherapeutic agent doxorubicin amplifying toxicity decreasing efflux doxorubicin. both amplified when used combination, this study raises possibility combinatorial therapy whose basis constitutes enhancing redox perturbation strategy kill [Mol Cancer Ther 2007;6(9):2544–53]