Bio-mimetic strategies to re-activate apoptotic cell death for cancer treatments

Apoptosis is a crucial process to maintain the correct balance between healthy cells and committed-to-death cells in every tissue. The internal (or mitochondrial) and external (or death receptor) pathways are responsible for driving a series of molecular events that lead to apoptosis by releasing pro-apoptotic proteins, such as B-cell lymphoma-2 (BCL-2) homology 3 (BH3)-only proteins and second mitochondria-derived activator of caspases/diablo inhibitor of apoptosis protein-binding mitochondrial protein (SMAC/DIABLO), that in turn activate the caspase family of proteases. By counterbalancing the apoptogenic machinery, anti-apoptotic BCL-2 family members turn off pro-apoptotic signalling, favouring cell survival, a circumstance that is particularly pronounced in tumour cells in which apoptosis is deranged. Therefore, targeting the defective apoptotic process has become a viable therapeutic option for the treatment of several cancers and much effort is being made in the research and development of effective compounds. This review discussed and updated the most promising therapeutic strategies that target deranged apoptosis process in cancer by mimicking the pro-apoptotic effects of BH3-only and SMAC/DIABLO proteins.