Sodium butyrate sensitizes human glioma cells to TRAIL-mediated apoptosis through inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP

摘要: In TNF-related apoptosis-inducing ligand (TRAIL)-resistant glioma cells, co-treatment with nontoxic doses of sodium butyrate and TRAIL resulted in a marked increase TRAIL-induced apoptosis. This combined treatment was also cytotoxic to cells overexpressing Bcl-2 or Bcl-xL, but not normal human astrocytes, thus offering an attractive strategy for safely treating resistant gliomas. Cotreatment facilitated completion proteolytic processing procaspase-3 that partially blocked by alone. We found significantly decreased the protein levels survivin X-linked inhibitor apoptosis (XIAP), two major caspase inhibitors. Overexpression XIAP attenuated butyrate-stimulated apoptosis, suggesting its involvement conferring resistance cells. Furthermore, kinase activities Cdc2 Cdk2 were following treatment, accompanying downregulation cyclin A B, as well upregulation p21. Forced expression plus A, butyrate/TRAIL-induced overriding butyrate-mediated XIAP. Therefore, Cdc2-mediated may contribute recovery sensitivity