An Overview of Apoptosis
Apoptosis, or “programmed cell death,” is a series of biochemical events resulting in characteristic cell changes (e.g., blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay) and eventual death. It is a highly controlled, regulated process that ensures the normal development and biological function of adult tissues.
Apoptosis: What Role Does It Play?
While the idea of dying cells may not sound like a good thing, it can actually be beneficial, even essential to the organism. There is an appointed time for old and damaged cells to die, self-destruct, and be eliminated from the body. Otherwise, there would be no place for new cells, and life wouldn’t have developed the way we knew it.
Without apoptosis, things like the shedding of old skin cells, the replacement of the lining of the digestive tract, and the renewal of red blood cells wouldn’t be possible. There wouldn’t even be a way to get rid of damaged and abnormal cells that can be harmful to the organism.
Apoptosis is crucial for maintaining a healthy immune system. As B-cells and T-cells are produced, they are tested to see if they will attack the host’s “self” components, and those that do are immediately eliminated through apoptosis. This ideally prevents self-reactive cells from being released into the body, which may lead to the development of autoimmune conditions, neurodegenerative disorders, and cancer.
Apoptosis is also responsible for clearing away all the excess pathogen-specific immune cells that were produced in response to an infection. After the pathogen is destroyed, there is no more need for the immune cells, so they are removed to maintain homeostasis in the immune system.
Apoptosis and Cancer
Apoptosis plays a crucial role in preventing the development of cancer. Under normal conditions, cells with damaged DNA, virus-infected cells, and precancerous cells would undergo programmed cell death to control intracellular infections and protect the surrounding healthy cells.
If anything goes seriously wrong in a cell and the damage is far beyond repair, the intrinsic (or mitochondrial) pathway is triggered, sending the cell into a self-destruct mode. This ensures that the damaged cells will not pass on their abnormalities to the succeeding generation of new cells, thereby successfully stopping cancer in its track.
Unfortunately, there are times when this crucial safeguard is bypassed. There are times when cells with badly damaged DNA fail to activate the internal apoptosis cues.
Will cancer cells start to proliferate when this happens? It depends. There is still a chance that the ever-vigilant immune cells will detect the presence of these precancerous cells and trigger the external signaling pathway to do its job before any further damage is done. If this fails, the precancerous cells will start to develop into full-blown cancer cells.
Worse, the failure to initiate apoptosis may also increase the risk of the cancer cells metastasizing or moving to another part of the body, causing cancer to spread even further.
Why do some precancerous cells escape apoptosis?
This usually happens when the p53 tumor suppressor, the protein responsible for detecting DNA damage and activating DNA repair proteins, is somehow inactivated. Protein p53, also known as the “guardian of the genome,” (we’d like to watch that movie) plays a significant role in conferring genomic stability, preventing genome mutation, and triggering apoptosis when the DNA damage is deemed beyond repair.
Cancer cells also evade apoptosis when the anti-apoptotic Bcl-2 family members and inhibitors of apoptosis proteins (IAPs) are upregulated. When this happens, Bcl-2 binds BAX and BAK proteins, preventing pore formation and inhibiting the action of pro-apoptotic BH3 proteins. By avoiding cell death and allowing the proliferation of damaged cells, the tumor is provided with the ideal environment for continued growth.
Does apoptosis play a role in cancer treatment?
Yes, apoptosis has a crucial role in cancer treatment. Through the use of radiation and chemotherapy drugs, the BH3 proteins gain additional strength to overcome the effects of anti-apoptotic Bcl-2 proteins. Chemotherapy drugs can force the cancer cells to undergo apoptosis, unless the cancer cells underwent a mutation that upregulated the specialized enzymes (i.e., caspase inhibitors) which cause cell death.
