Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 15, 2003
Publication Date: November 1, 2003
Citation: Park, J.B., Schoene, N.W. 2003. A phenylpropenoic acid derivative, n-caffeolytyramine, is a potent phytochemical to induce apoptosis of human transformed myeolocytic u937 and hl-60 and lymphocytic jurkat cells. Journal of Natural Products. Interpretive Summary: Phytochemicals have been an excellent resource for drug discoveries because they have potent effects on various diseases such as heart and neural diseases, diabetes, and cancers. Particularly, research has been performed to explore their potent effects on cancers, but the anti-proliferation effects of many phytochemicals remain to be investigated. This report describes synthesis, chemical characterization and the anti-proliferation effects of N-coumaroyltyramine analogues, because N-coumaroyltyramine shares a considerable structural resemblance to experimental cancer drugs. Among the analogues studied, N-caffeoyltyramine was the most potent compound exhibiting growth inhibition of human tumor cells, and the cell growth inhibition followed an increase in apoptotic enzymes and a decrease in protein tyrosine kinase activity, which may lead to programmed cell death. The outcomes of current and future studies will provide researchers in nutrition, molecular biology, and medicinal fields novel information regarding its suitability as a dietary factor for reducing risks of chronic diseases such as cancer.
Technical Abstract: Phytochemicals consist of many diverse compounds which may have beneficial effects on chronic diseases such as diabetes, heart disease, and cancers. Previously, a phenylpropenoic acid derivative, N-coumaroyltyramine, was reported to arrest human transformed cells at S-phase of the cell cycle by inhibiting protein tyrosine kinases. Due to the potency of N-coumaroyltyramine, its analogues (N-cinnamoyltyramine, N-caffeoyltyramine, N-feruloyltyramine, and N-sinapoyltyramine) were investigated to determine their anti-proliferation effect on human transformed cells and to identify the structural moieties accountable for the activity. Due to the scarcity of N-coumaroyltyramine analogues, in this study they were chemically synthesized and purified by HPLC. New peaks in HPLC chromatograms were further purified and confirmed by LC-MS as N-coumaroyltyramine analogues with the appropriate mass/charge (m/z) units. The decreasing order of anti-proliferation activity was N-caffeoyltyramine > N-coumaroyltyramine > N-feruloyltyramine > N-sinapoyltyramine > N-cinnamoyltyramine. N-caffeoyltyramine was the most potent, inhibiting growth of several human transformed cell lines (HL-60, U937, Jurkat cells) by approximately 90% at a concentration of 10 micrometers. It also induced cell growth arrest at S-phase of the cell cycle. The cell growth inhibition followed an increase in caspase-3 activity and a decrease in protein tyrosine kinase activity which may have led to programmed cell death. These novel data indicate that N-caffeoyltyramine has potent anti-proliferation activity and the compound may induce apoptosis of human tumor cells by inducing caspase-3 activity.