"What is Apoptosis?"
TUMOR TIDBITS, A BIWEEKLY EMAIL NEWSLETTER FROM GULF COAST VETERINARY ONCOLOGY
Number 79; November 22, 2002.

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THIS WEEK'S TUMOR TIDBIT:  What is Apoptosis?

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Apoptosis is a mechanism of controlled cell death critically important in many biological  
processes.  The scientific community has long acknowledged the distinct morphological 
pattern  exhibited by certain dying cells.  Apoptosis is a specific controlled mechanism 
of cell death  distinct from uncontrolled necrotic death.  The concept that death is 
essential for life is  intriguing.  In the last decade there has been an explosion of 
interest with apoptosis becoming  one of the most widely used words in medicine and 
biology today, with ever increasing levels of  funding being made available for research 
into the subject.  

Apoptosis was used in medical terminology over 2000 years ago.  A common mistake is the  
mispronunciation of the word “apoptosis”; the correct pronunciation is with the second  p   
silent (a-po-toe-sis).  In Greek, apoptosis means “dropping off” of petals or leaves from  
plants or trees.  The phrase had a medical meaning to the Greeks over two thousand of 
years  ago.  Hippocrates of Cos (460-370 BC) used the term to mean, “the falling off of 
the bones” and  Galen extended it’s meaning to “the dropping of the scabs”.  

To maintain homeostasis in the human body, an estimated 10 billion cells are made each day 
just  to balance those dying by apoptosis.  The balance between cell proliferation and 
apoptosis  regulates cell number.  It follows then that apoptosis’s role in normal 
physiology is as  significant as that of its counterpart, mitosis. It plays a 
complementary, but opposite, role  to mitosis in the regulation of cell populations. 

Contrary to necrosis (an uncontrolled, passive process results from extreme changes in the 
cell  microenvironment, such as exposure to toxic agents), apoptosis is controlled and  
energy-dependent.  Necrosis usually affects large fields of cells whereas apoptosis can 
affect  individual or clusters of cells.  Apoptosis is involved in a wide range of 
physiological and  pathological processes. Some examples of these processes are fetal 
development, inflammation  and involution of tissues, regulation of the immune system, and 
the ageing process. 

Apoptosis can be recognized by light and electron microscopy by its characteristic  
morphological features of cell shrinkage, chromatin condensation, cytoplasmic membrane  
blebbing, and phagocytosis of apoptotic bodies by neighboring cells.  There are many  
biochemical features of apoptosis.  Protein cleavage by caspases (the central executioners 
of  the apoptotic pathway) accounts for the distinctive cytoplasmic and structural changes 
seen in  apoptotic cells.  DNA breakdown by endonucleases is triggered by caspase 
activity.   Multiple  death promoting molecules, amplifying cascade effects and positive 
feedback loops all ensure  that the process, once initiated, is quick, fatal and 
irreversible.  As a fail-safe mechanism  the cell produces buffers (dampeners) to ensure 
that small, insignificant disturbances do not  lead to unnecessary death. 

Failure of apoptosis can lead to disease.  Apoptosis requires tight regulation. Lack of 
such  control, leading to either too much or too little apoptosis can have pathological 
consequences  such as autoimmune disease from the persistence of autoreactive T/B-cells; 
neurodegeneration,  as seen in Alzheimer’s and Parkinson’s disease, are consequences of 
excessive, premature  apoptosis of neurons in the brain; ischemia, with mild to moderate 
hypoxia resulting in a  non-functional region of tissue, which if it is sufficiently large 
may lead to organ failure;  and cancer caused by cells not dying, rather than a greater 
rate of proliferation. 
 
How can the power of apoptosis be used to our advantage?  The role of  apoptosis in each 
of  these diverse areas implicates immense potential for the manipulation of apoptosis to 
treat  disease. Research is already underway to harness apoptosis as a therapeutic tool in 
modern  medicine.  Possibilities include control of malignant disease, delay of premature 
senescence in  neurodegenerative disease, regulation of inflammatory disease, treatment of 
autoimmune  disorders, and minimizing the area of infarct in ischemic disease.
 

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We hope this info helps and don't hesitate to call us Gulf Coast Veterinary Oncology!

Kevin A. Hahn, DVM, Phd, Diplomate ACVIM (Oncology), drhahn@gcvs.com
Janet K. Carreras, VMD, Diplomate ACVIM (Oncology), drcarreras@gcvs.com
Glen K. King, DVM, MS, Diplomate ACVR (Radiology & Radiation Therapy), drking@gcvs.com

Gulf Coast Veterinary Diagnostic Imaging & Oncology
1111 West Loop South, Suite 150, Houston, TX 77027
P: 713.693.1166  F: 713.693.1167  W: www.gcvs.com