Programmed cell death, or apoptosis, is essential for maintaining homeostasis. As a mechanism to get rid of damaged, mutated, or unwanted cells, apoptosis is a crucial part of every cell cycle. However, once the regulatory function becomes impaired, it can lead to uncontrollable cell division and the subsequent formation of a tumor [National Human Genome].
When internal or external stimuli trigger the apoptotic pathway, a death signal is initiated. The message is then relayed to various organelles, such as the mitochondria, where it prepares for cell death by permeabilizing its membrane, known as mitochondrial outer membrane permeabilization (MOMP). By making the membrane more porous, mitochondrial intermembrane proteins are released into the cytosol, finalizing the death of the cell [Llambi and Green].
Unfortunately, cancerous cells acquire mutations that enable them to circumvent death by interfering with the apoptotic signal cascade. The presence of B-cell CLL/lymphoma 2 (Bcl-2) family proteins is a unique feature of tumorous cells, in which the cells never die [Brunelle and Letai]. The Bcl-2 protein family is categorized as either pro- or anti-apoptotic, and therefore is the key to maintaining the survival, or death, of a cell.
Cancer cells often overexpress anti-apoptotic proteins such as BCL-2, MCL-1, and BCL-XL. These pro-survival proteins prevent cell death by inhibiting pro-apoptotic proteins, which are essential in carrying out MOMP [Shamas-Din et al.]. When pro-apoptotic proteins are blocked, the death sentence of the cell is interrupted, which disrupts the cell’s regulating mechanisms.
BH3-only proteins, a specific class of the pro-apoptotic Bcl-2 family, are distinguished for sharing only the BH3 (Bcl-2 homol...
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