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

<p>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.</p>