ROS-dependent prostate apoptosis response-4 (Par-4) up-regulation and ceramide generation are the prime signaling events associated with curcumin-induced autophagic cell death in human malignant glioma

摘要: Malignant gliomas are extremely resistant to therapies that induce apoptosis, but less autophagy. Therefore, drugs targeting autophagy promising in the management of malignant gliomas. In this study, we investigated anti-glioma potential curcumin vitro, and further examined molecular mechanisms curcumin-induced cell death human glioma. Here, provide evidence is cytotoxic against glioma lines, mechanism caused by associated with features Curcumin suppresses growth cells via ROS-dependent prostate apoptosis response-4 (Par-4) induction ceramide generation. Extracellular supplementation antioxidants such as glutathione N-acetylcysteine abrogated Par-4 induction, generation, turn, prevented autophagic death. Moreover, tumor transfected gene sensitized Overall, study describes a novel signaling pathway which induces activation leading cells.