Apoptosis, also called programmed cell death (PCD) is one of the most important cell processes. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death that is of importance for normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. Apoptotic cell death is triggered by extrinsic, receptor-mediated, or intrinsic, mitochondria-mediated, signalling pathways that induce death-associated proteolytic and/or nucleolytic activities. The six important targets which directly related to apoptosis are caspase which is the biomarker of apoptosis , TNF-alpha which is a important cytokine involved in cancer, p53 which is a famous tumor suppressor protein, bcl-2 family proteins which is apoptosis regulator proteins and Survivin which is a member of the inhibitor of apoptosis (IAP) family. Researchers pay more attention to bcl-2 inhibitors which are ABT-263 (Navitoclax), ABT-737, Obatoclax Mesylate (GX15-070) and Lenalidomide. ABT-737 is a Bcl-2 antagonist that targets Bcl-2/Bcl-xL which may inhibit cell death. It’s a selective inhibitor of bcl-2 which does not target mcl-1 so that it can induce apoptosis of cancer cell line. ABT-737 is different from ABT-263 which lead to apoptosis by disrupting Bcl-2/Bcl-xL interactions with pro-apoptosis protein such as Bim.

Apoptosis and Disease

Apoptosis, in general, confers advantages during an organism's life cycle. Between 50 billion and 70 billion cells die each day due to apoptosis in the average human adult. In a year, this amounts to the proliferation and subsequent destruction of a mass of cells equal to an individual's body weight. Inappropriate apoptosis is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its profound therapeutic potential, and research continues to focus on the elucidation of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis.