Figure 1.

Effects of BH3-mimetic drugs. Overexpression of proteins of the Bcl-family in tumor cells cause capture of Bak and Bax in BH3-binding sites, which prevents initiation of the apoptosis cascade via intrinsic or extrinsic stimuli (A); BH3-mimetic drugs lead to the release of Bak and Bax, which oligomerize and insert as a complex in the outer mitochondrial membrane. This membrane permeabilisation is followed by cytochrome c release and other pro-apoptotic factors into the cytoplasm, initiating apoptosis and leading to cell death (B); BH3-mimetic drugs can enhance dead signals from immune cells (TRAIL, TNF-α) and can influence migration of tumor cells (C).