title: Caffeic acid and quercitrin purified from Houttuynia cordata inhibit DNA topoisomerase I activity.
abstract: A methanol extract of Houttuynia cordata showed an inhibitory effect on mammalian DNA topoisomerase I. Two topoisomerase I inhibitory compounds were purified and identified as caffeic acid and quercitrin. Caffeic acid and quercitrin inhibited the activity of topoisomerase I with IC(50) values of about 0.15 and 0.05 mM, respectively. A concentration of 45 µM caffeic acid caused 50% growth inhibition in human leukaemia U937 cells, but not on those of normal fibroblast NIH3T3 cells. However, quercitrin mysteriously stimulated proliferation of U937 and NIH3T3 cells. Caffeic acid-induced cell death was characterised with the cleavage of poly (ADP-ribose) polymerase and procaspase-3, indicating that this inhibitor triggered apoptosis. The apoptotic induction by caffeic acid was also confirmed using flow cytometry analysis. Because DNA topoisomerase I is an important target for tumour chemotherapy, the present study suggests that caffeic acid, but not quercitrin, may function by suppressing oncogenic disease through the inhibition of cellular topoisomerase I activity.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Seok-Young
authors.initials: SY
authors.lastname: Jang
authors.forename: Jeen-Soo
authors.initials: JS
authors.lastname: Bae
authors.forename: Yun Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Kyeong Yeol
authors.initials: KY
authors.lastname: Oh
authors.forename: Ki-Hun
authors.initials: KH
authors.lastname: Park
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D052859:Houttuynia; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D002109:Caffeic Acids; D004365:Drugs, Chinese Herbal; C442781:Houttuynia cordata extract; C012526:quercitrin; D011794:Quercetin; D004264:DNA Topoisomerases, Type I; C040048:caffeic acid