Caffeic acid and quercitrin purified from Houttuynia cordata inhibit DNA topoisomerase I activity

• Published in: Natural product research Vol. 25; no. 3; pp. 222 - 231
• Main Authors: Jang†, Seok-Young, Bae†, Jeen-Soo, Lee, Yun Ho, Oh, Kyeong Yeol, Park, Ki-Hun, Bae, Young-Seuk
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.02.2011
• Subjects: Animals; anti-tumour drug; apoptosis; caffeic acid; Caffeic Acids - chemistry; Caffeic Acids - isolation & purification; Caffeic Acids - pharmacology; Cell Line, Tumor; chemotherapy; DNA topoisomerase; DNA topoisomerase I inhibitor; DNA Topoisomerases, Type I - metabolism; Drugs, Chinese Herbal - chemistry; Enzyme Activation - drug effects; fibroblasts; flow cytometry; growth retardation; Houttuynia cordata; human leukaemia cells; Humans; inhibitory concentration 50; leukemia; methanol; Mice; NIH 3T3 Cells; Quercetin - analogs & derivatives; Quercetin - chemistry; Quercetin - isolation & purification; Quercetin - pharmacology; quercitrin
• ISSN: 1478-6427; 1478-6419; 1478-6427
• DOI: 10.1080/14786410903339044

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 IC₅₀ 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.