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<scp>CSC</scp> ‐3436 sensitizes triple negative breast cancer cells to <scp>TRAIL</scp> ‐induced apoptosis through <scp>ROS</scp> ‐mediated p38/ <scp>CHOP</scp> /death receptor 5 signaling pathways
- Source :
- Environmental Toxicology. 36:2578-2588
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) shows little or no toxicity in most normal cells and preferentially induces apoptosis in a variety of malignant cells. However, patients develop resistance to TRAIL, therefore, sensitizing agents that can sensitize the tumor cells to TRAIL-mediated apoptosis are necessary. In this study, we investigated the effect of 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), an useful flavonoid, to overcome the TRAIL-resistant triple negative breast cancer (TNBC) cells. We found that CSC-3436 potentiated TRAIL-induced apoptosis in TRAIL-resistant TNBC cells and this correlated with the upregulation of death receptors (DR)-5 and down-regulation of decreased decoy receptor (DcR)-1 expression. When examined for its mechanism, we found that the decreased expression of anti-apoptotic proteins c-FLIPS/L, Bcl-Xl, Bcl-2, Survivin, and XIAP. CSC-3436 would increase the expression of Bax and promoted the cleavage of bid. In addition, the induction of DR5 by CSC-3436 was found to be dependent on the modulation of reactive oxygen species (ROS)/p38/C/EBP-homologous protein (CHOP) signaling pathways. Overall, our results indicated that CSC-3436 could potentiate the apoptotic effects of TRAIL through down-regulation of cell survival proteins and upregulation of DR5 via the ROS-mediated upregulation of CHOP protein.
Details
- ISSN :
- 15227278 and 15204081
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Environmental Toxicology
- Accession number :
- edsair.doi...........136039b49e53b2a9e6aca33b804770d6