Abstract
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.
MeSH terms
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Acylation
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Aorta, Thoracic / drug effects
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Capillaries / drug effects
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Catechin / analogs & derivatives*
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Catechin / chemical synthesis*
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Catechin / pharmacology
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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DNA Polymerase I / antagonists & inhibitors*
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DNA Polymerase beta / antagonists & inhibitors*
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Drug Screening Assays, Antitumor
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Endothelial Cells / cytology
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Endothelial Cells / drug effects
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Flavonoids / chemical synthesis
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Flavonoids / pharmacology*
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HL-60 Cells
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Humans
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In Vitro Techniques
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Male
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Neovascularization, Physiologic / drug effects
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Rats
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Rats, Wistar
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Recombinant Proteins / antagonists & inhibitors
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Stearates / chemical synthesis
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Stearates / pharmacology*
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Umbilical Veins / cytology
Substances
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(2R,3S)-3',4',5,7-tetrahydroxyflavan-3-yl octadecanoate
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Flavonoids
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Recombinant Proteins
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Stearates
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Catechin
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DNA Polymerase I
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DNA Polymerase beta