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Figure 8 | BMC Cancer

Figure 8

From: A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

Figure 8

Working model of Smac-mimetic IAP-antagonist sensitizing TRAIL-induced apoptosis by suppressing NF-κB. TRAIL triggers apoptosis via both the death-receptor (DR4/DR5) and mitochondrial pathways, by activating initiator caspase-8 and -9, and effector caspase-3. Furthermore, both Bid and PARP are cleaved by caspases, which are typical predictors of TRAIL-mediated apoptosis. A Smac-mimetic effectively blocks IAP (XIAP/cIAP-1) function and facilitates caspase activation. Simultaneously, the Smac-mimetic suppresses TRAIL-induced classical NF-κB activation by preventing IκBα degradation and RelA nuclear translocation. Blockade of NF-κB - XIAP signaling by small molecule Smac-mimetic abolishes counteraction of pro-survival factors on TRAIL-mediated apoptosis.

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