Epicatechin conjugated with fatty acid is a potent inhibitor of DNA polymerase and angiogenesis.
Anti-cancer and anti-angiogenesis effects of green tea catechins have been demonstrated. It has been found that chemical modification of tea catechins improves their biological activities. We examined the chemical modification of epicatechin enhanced anti-cancer and anti-angiogenic effects. Epicatechin conjugated with fatty acid (acyl-catechin) strongly inhibited DNA polymerase activity, HL-60 cancer cell growth and angiogenesis. Epicatechin conjugated with palmitic acid ((2R,3R)-3',4',5,7-tetrahydroxyflavan-3-yl hexadecanoate, epicatechin-C16) was the strongest inhibitor in DNA polymerase alpha, beta, lambda and angiogenesis assays. Epicatechin-C16 also suppressed human endothelial cell (HUVEC) tube formation on reconstituted basement membrane, suggesting that it affected not only DNA polymerase activity but also the signal transduction pathways needed for the tube formation in HUVECs. These results suggest that acylation of epicatechin is an effective chemical modification to improve the anti-cancer activity of epicatechin.
Matsubara
Kiminori
K
Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama 719-1197, Japan. kmatsuba@fhw.oka-pu.jp
Saito
Akiko
A
Tanaka
Akira
A
Nakajima
Noriyuki
N
Akagi
Reiko
R
Mori
Masaharu
M
Mizushina
Yoshiyuki
Y
D000215:Acylation; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019384:Nucleic Acid Synthesis Inhibitors; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D019308:Palmitic Acid; D002392:Catechin