The proposed mechanism of enhanced apoptosis by a combination of casticin and TRAIL in gastric cancer cells.

Casticin initially promotes ROS generation and triggers ER stress, then induces DR5 upregulation through the activation of CHOP which then enhances TRAIL-induced activation of DR5-induced and mitochondria-mediated apoptosis pathways. Simultaneously, casticin facilitates TRAIL-induced apoptotic cell death by inhibition of anti-apoptosis protein (cFLIP, Bcl-2, survivin and XIAP) expression and activation of pro-apoptosis proteins.