Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death

Oncotarget. 2021 Aug 3;12(16):1615-1626. doi: 10.18632/oncotarget.28031.


Cancer is a global public health concern that is characterized by the uncontrolled growth of tumor cells. It is regarded as the subsequent cause of death after cardiovascular disease. The most common types of cancer include breast, colorectal, lung, and prostate. The risk factors attributed to the development of common types of cancer are tobacco smoking, excessive alcohol consumption, dietary factors, ultraviolet radiation (UV), and lack of physical activities. Two major cellular apoptotic pathways targeted in cancer therapies are intrinsic and extrinsic. These two pathways are regulated by different types of proteins, the multidomain pro-apoptotic proteins (Bak, Bax, and Bok), BH3-only pro-apoptotic proteins (Bid, Bim, Bad, Noxa, and Puma), and the anti-apoptotic proteins (Mcl-1, Bfl-1, Bcl-XL, Bcl-2, Bcl-w, and Bcl-B). Other significant molecules/factors that are known to execute cellular apoptotic pathways include bioactive compounds, and reactive oxygen species (ROS). Proteolytic caspases are known to play a vital role in the initiation of apoptotic activities in cancerous cells. Based on their functions, they are categorized into initiators and executioners. Nanotechnology has produced novel outcomes in modern medicine. The green synthesis of nanoparticles has demonstrated prospective improvements in cancer therapies in combination with the existing therapies including photodynamic therapy. This review aims at highlighting the association between pro-apoptotic and anti-apoptotic proteins, and their significance in cancer therapy.

Keywords: Bcl-2 family proteins; apoptosis; cancer; caspases; p53.