Downregulation of X-linked inhibitor of apoptosis protein by '7-Benzylidenenaltrexone maleate' sensitizes pancreatic cancer cells to TRAIL-induced apoptosis.

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential biological anticancer agent. However, a wide range of human primary cancers, including pancreatic cancer, display resistance to apoptosis induction by TRAIL. Therefore, this resistance needs to be overcome to allow TRAIL to be successfully used in cancer therapy. In this study, we performed a compound screen to isolate TRAIL sensitizers and found that one of the identified compounds, 7-benzylidenenaltrexone maleate (BNTX), sensitized pancreatic cancer cells to TRAIL-induced apoptotic cell death. The combination of BNTX with TRAIL promoted the release of cytochrome c from mitochondria into cytosol with caspase activation and a resulting increase in annexin V-stained cells. From a mechanistic perspective, w

SUBMITTER: Kim SY 

PROVIDER: S-EPMC5617406 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature