Catechin conjugated with fatty acid inhibits DNA polymerase and angiogenesis.
Catechins in green tea have anticancer and antiangiogenesis activities, with epigallocatechin-3-gallate (EGCG) being the most potent antiangiogenic tea catechin. This study examined whether chemical modification of catechin enhanced anticancer and antiangiogenic effects. Catechin, conjugated with fatty acid (acyl-catechin), strongly inhibited DNA polymerase, HL-60 cancer cell growth, and angiogenesis. Catechin conjugated with stearic acid [(2R,3S)-3',4',5,7-tetrahydroxyflavan-3-yl octadecanoate; catechin-C18] was the strongest inhibitor in DNA polymerase alpha and beta and angiogenesis assays. Catechin-C18 also suppressed human endothelial cell (HUVEC) tube formation on the reconstituted basement membrane, suggesting that it affected not only DNA polymerases but also signal transduction pathways in HUVECs. These data indicate that acyl-catechins target both DNA polymerases and angiogenesis as anticancer agents. These results suggest that acylation of catechin is an effective chemical modification to improve the anticancer activity of catechin.
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.ac.jp
Saito
Akiko
A
Tanaka
Akira
A
Nakajima
Noriyuki
N
Akagi
Reiko
R
Mori
Masaharu
M
Mizushina
Yoshiyuki
Y
D000215:Acylation; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors*; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005419:Flavonoids / Q000138:chemical synthesis / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013228:Stearates / Q000138:chemical synthesis / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
C509175:(2R,3S)-3',4',5,7-tetrahydroxyflavan-3-yl octadecanoate; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005419:Flavonoids; D011994:Recombinant Proteins; D013228:Stearates; D002392:Catechin; D004256:DNA Polymerase I; D019951:DNA Polymerase beta