The Effects Of Caffeic Acid Phenethyl Ester On Antioxidation, Pro-oxidation And Relative Mechanism Of Anti-angiogenesis

After the recent explosion of research in the cell physiology and pharmacology of free radical, further investigation in this field has attraced more and more attention. It is now commonly recognized that reactive oxygen species (ROS) plays important roles in the regulation of life processes. In particular, lipid peroxidation, DNA and protein damage mediated by oxidative stress are associated with a variety of chronic health problems, such as carcinogenesis, ageing and neurodegenerative disorders. Some plant-derived antioxidants have been reported to be beneficial in protecting against these diseases, and as chemopreventive agents have received much attention among the public and the medical community. In the present thesis, caffeic acid phenethyl ester (CAPE), a natural polyphenol derived from propolis and its relative antioxidants, i.e. caffeic acid (CA), ferulic acid (FA) and ethyl ferulate (EF), were used to test their various antioxidative potentials, Cu(II)-dependent pro-oxidative activities, anti-tumor angiogenesis activities and potential mechanisms.1) The various antioxidant effects of CAPE and its relative polyphenolic antioxidants extracted from propolis against lipid peroxidation, oxidative DNA and protein damage were studied. And it was shown that CAPE, which has ortho-dihydroxyl functionality and high level of lipophilicity, shows highest effects among the tested compounds.2) In the presence of Cu (II), CAPE and its relative polyphenolic antioxidants caused breakage of supercoiled plasmid pBR 322 DNA and calf thymus DNA. Caffeic acid and ester which have ortho-dihydroxyl functionality show highest effects among the tested compounds. As a cancer chemopreventive drug, such prooxidant effects contributed to elicit potential genotoxicity may be its important mechanism of anticancer and apoptosis-inducing properties.3) Angiogenesis is a complex physiological and pathological process that includes endothelial cell activation, extracellular matrix degradation, endothelial cell migration, proliferation and new vessels formation. The process is tightly regulated by various factors. Reactive oxygen species (ROS) are believed to play important roles in the regulation of angiogenesis. The inhibition effects of CAPE and its relative polyphenolic antioxidants on angiogenesis activities induced by H₂O₂ were studies in vivo and vitro. Otherwise, their cytotoxicities on three tumor cell lines (PC-3, MCF-7 and EJ cells) was futher studied in the present work. It was found that polyphenolic esters, which bears ortho-diphenoxyl group, exhibited the most potent anti-angiogenesis activity, and the 4-hydroxyl-3-methoxylphenyl group seems to play critical roles.