Omega-3 Fatty Acids: Docosahexaenoic Acid (DHA)
EPA eicocipentanoiko Acid
It is our aim to understand how the omega-3 fatty acid docosahexaenoic acid (DHA) affects both cancer cells and immune cells (lymphocytes) that eliminate cancer, so that we can devise rational cancer therapies involving DHA.
It has long been recognized that diets rich in fish are beneficial for human health.
Omega-3 fatty acids, abundant in cold water fish, provide much of that health benefit, as they have been shown to be essential for normal Neurological Development And Vision, as well as being beneficial in diverse diseases such as
- and certain cancers.
It is still unknown, however, how omega-3 fatty acids exert their benefit, and these mechanisms of action are likely to be diverse.
We study how the omega-3 fatty acid DHA affects membranes because membranes are fundamental to all cells, and when lymphocytes attack cancer cells, much of the immunologic attack occurs at the plasma membranes of the cells.
Fatty acids comprise the hydrophobic interior of membranes, and the presence of DHA among these fatty acids INCREASES membrane permeability, fusion, and affects proteins residing in the membrane.
Membrane proteins play various roles in lymphocyte attack on cancer.
On the cancer cell, proteins called class I major histocompatibility complex (MHC I) molecules alert lymphocytes that the cancer cell is abnormal, that is, bears tumor antigens.
On the lymphocyte, antigen receptors detect MHC I/tumor antigen complexes and lead to lymphocyte activation; accessory membrane proteins help with the activation process, and a variety of other membrane proteins participate in the lymphocyte response that eventually leads to cancer cell destruction.
What is happening at the cell membranes that produces DHA’s beneficial effect in reducing growth of certain cancers?
We believe that membranes are not homogeneous cell coats but rather are complex structures divided into many different patches called domains.
Different domains have different lipid and protein compositions, and thus support different membrane activities.
Our basic hypothesis is that DHA induces distinct domains in cell membranes, and that membrane proteins segregate selectively into the various domains. As a result, membrane protein activities are changed, and the cellular activities carried out by these proteins are affected.
In the case of immunity to cancer, proteins involved in lymphocyte recognition and destruction of cancer cells, and the growth potential of the cancer cells themselves, are affected by DHA-induced domain formation.
The current projects in the lab fall into three categories.
1. Isolation of putative, DHA-induced membrane domains, and characterization of their lipid and protein (particularly MHC I) content.
2. Exploration of the effect of different lipid environments on membrane protein (MHC I, Thy-1) conformation, lateral movement, and clustering.
3. Investigation of DHA’s effect on lymphocyte activation and function, and cancer cell proliferation and viability. DHA may be used as a nutrient (as a model for dietary enrichment with DHA) or a drug (as a model for drug delivery in liposomes composed of DHA).