DATS sensitizes glioma cells to TRAIL-mediated apoptosis by up-regulation of death receptor 5 via ROS

- Apoptotic cell death is induced by combination of DATS with TRAIL.
- DATS increased DR5 via p53 protein in glioma cells.
- Upregulation of DR5 receptors through actions on the ROS- induced-p53 by DATS.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a promising anticancer reagent for antitumor therapy. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL, due to repeat treat to cancer cells, highlighting the need for strategies to overcome TRAIL resistance. Here we present that in combination with diallyl trisulfide (DATS), exposure to TRAIL induced apoptosis in TRAIL-resistant glioma cells. Surprisingly, we found that subtoxic concentrations of DATS significantly potentiated TRAIL-induced cytotoxicity and apoptosis in glioma cells. DATS dramatically upregulated DR5 receptor expression but had no effects on DR4 receptor. In addition, DATS enhances TRAIL-induced apoptosis through the downregulation of anti-apoptotic protein (Mcl-1) and the upregulation of DR5 receptors through actions on the ROS- induced-p53.