2008 Annual Report
1a.Objectives (from AD-416)
1) To synthesize N-coumaroyltyramine and its analogues and to identify their cellular effects and molecular mechanisms, particularly as related to cancer modulation,.
2)To assess anti-cancer and other health effects N-coumaroyltyramine and its analogues in an animal model.
1b.Approach (from AD-416)
1. Synthesis of phenylpropenic acid conjugates (N-coumaroyltyramine and its analogues). 2. Measurement of phenylpropenic acid conjugates in cell and biological samples. 3. Investigation of effects of phenylpropenic acid conjugates on cell cycle and growth of cancer cells. 4. Apoptosis study. 5. Hydrogen peroxide quenching study. 6. Investigation of effects of phenylpropenic acid conjugates on MAPK Kinases. 7. Investigation of effects of phenylpropenic acid conjugates on protein tyrosine kinase including EGFR. 8. Investigation of effects of phenylpropenic acid conjugates on xenograft tumor in nude mice.
Health benefits of fruits and vegetables are well documented; however, there is little information regarding the potential beneficial effects of phenolic conjugates found in plants on human health. Studies of phenolic conjugates have been hindered because these compounds are not commercially available, an important requirement to study specific effects of a compound. In this research progress has been made in the synthesis and/or purification by HPLC of several phenolic conjugates including caffedymine-type and safflomide-type phenylpropenoid acid amides and chlorogenic acid found in coffee and cocoa. The bioavailability and biological actions of these phenolic conjugates were investigated in order to validate their purported activities. Animal models and cell culture systems have been developed to test the effects of these phenolic conjugates on the cellular and molecular events critical to the initiation and/or progression of human chronic diseases such as cardiovascular disease, inflammation, and cancer. To date, the effects of these conjugates on mechanisms that lead to these diseases, such as changes in signal transduction pathways, cell-cell interaction, cell activation, cell proliferation, and cell death (apoptosis) using reverse transcription polymerase chain reaction (RT-PCR), flow cytometry, and several biochemical assays, have been evaluated. The objectives fit well with NP107 Human Nutrition Action Plan 2004-2008 Component 5. Health Promoting Properties of Plant and Animal Foods.
Specific polyphenols found in coffee, cocoa, and tea affect blood platelet-leukocyte interactions. N-caffeoyltyramine, N-caffeoyldopamine, and N-couamroyldopamine, three phenylpropenoic acid amides found in coffee, cocoa, and/or tea, were synthesized, purified, and studied to determine their effects on P-selectin expression and platelet-leukocyte interactions because these cell-cell interactions are important physiological processes involved the initiation of cardiovascular disease, inflammation, and cancers. N-caffeoyldopamine and N-caffeoyltyramine were the most potent phenolic conjugates found to inhibit P-selectin expression and platelet-leukocyte interactions in cell culture and animal models. In addition, N-caffeoyldopamine and N-caffeoyltyramine were found to inhibit cycloxygenase (COX) activity which is a major target for the control of cardiovascular and inflammatory diseases. This suggests that foods rich in these substances could be useful for the prevention of these disorders and have fewer adverse effects. The objectives fit well with NP107 Human Nutrition Action Plan 2004-2008 Component 5. Health Promoting Properties of Plant and Animal Foods.
5.Significant Activities that Support Special Target Populations
|Number of the New MTAs (providing only)||1|
|Number of Invention Disclosures Submitted||1|
|Number of Web Sites Managed||1|
Park, J.B. 2008. Serotomide and safflomide modulate forskolin-stimulated cAMP formation via 5-HT1 receptor. Phytomedicine. http://dx.doi.org/10.1016/j.phymed.2008.04.009.