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We investigated the effect of casticin on apoptosis induced by tumor necrosisfactor (TNF)-related apoptosis-inducing ligand (TRAIL). We found that casticinpotentiated TRAIL-induced apoptosis in human colon cancer cells. Casticin downregulatedcell survival proteins including Bcl-xL, Bcl-2, survivin, XIAP and cFLIP, andinduced death receptor 5 (DR5), but had no effect on DR4 and decoy receptors (DcR1or DcR2). Deletion of DR5 by siRNA significantly reduced the apoptosis inducedby TRAIL and casticin. In addition, casticin induced reactive oxygen species (ROS)generation in a dose-dependent manner. Collectively, the present study showedthat casticin potentiates TRAIL-induced apoptosis through downregulation of cellsurvival proteins and induction of DR5 mediated by ROS.

Casticin, a flavonoid, potentiates TRAIL-induced apoptosis through modulation of anti-apoptotic proteins and death receptor 5 in colon cancer cells