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. Author manuscript; available in PMC: 2014 Oct 1.
Published in final edited form as: J Cell Physiol. 2013 Oct;228(10):1996–2005. doi: 10.1002/jcp.24362

Figure 6. Molecular mechanisms by which Sorafenib, HDAC inhibitors, TRAIL and obatoclax kill hepatoma cells.

Figure 6

TRAIL activates the death receptors DR4 and DR5. Obatoclax (GX) inhibits the protective BCL-2 family proteins BCL-XL and MCL-1. Sorafenib + HDAC inhibitor treatment has multiple targets; reduced expression of anti-apoptotic protein expression (FLIP, BCL-XL, MCL-1) and activation of BAX, BAD, BIM and NOXA. Thus [sorafenib + HDAC inhibitor] treatment facilitates TRAIL lethality by decreasing the levels of FLIP, BCL-XL, MCL-1 and activation of toxic BH3 domain proteins, whereas obatoclax can only facilitate the actions of [sorafenib + HDAC inhibitor] treatment on protective BCL-2 family proteins.