The Role of the Enzyme Acid Ceramidase in the Etiology of Cancer

Ceramide belongs to a class of bio-active organic compounds referred to as sphingolipids.

  

This class of compounds has been shown to play important roles in many cellular processes including cell growth and proliferation, growth arrest and most importantly, apoptosis – programmed cell death.  Furthermore, research studies have strongly implicated sphingolipid signaling dysfunction in tumor progression – metastasis.  In addition, sphingolipids seem to play a role in the effect of chemotherapy and radiation upon cancer progression in patients with metastatic disease.

The current data strongly suggests that the enzyme acid ceramidase (AC) is implicated in both tumor growth and resistance to various therapeutic modalities as suggested above.  AC is an enzyme that catalyzes the breakdown of ceramide to sphingosine and fatty acid (see diagram below).  

AC over expression has been found in association with certain metastatic cancers including prostate cancer.  A decrease in the intracellular levels of ceramide has been shown to result in a decrease in apoptosis that would ordinarily lead to cell death for proliferating tumor cells.

As a consequence of these data, Daniele Piomelli, the Louise Turner Arnold Chair in Neurosciences at UCI, and colleagues at the Italian Institute of Technology, have also established an association with over expression of AC and metastatic disease in melanoma patients.  This group has proceeded to successfully develop drugs that effectively inhibit AC in an attempt to restore an appropriate level of apoptosis and slow down tumor progression.

This approach is experimentally sound and has been shown to be efficacious in in-vitro experiments with cancerous cells in culture.  This