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 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.

Keywords:

• Houttuynia cordata
• DNA topoisomerase I inhibitor
• caffeic acid
• quercitrin
• human leukaemia cells
• anti-tumour drug

Acknowledgement

This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean Government (MOST) (No. 200-01-030).

Notes

^†Authors have contributed equally to this work.

Additional information

Notes on contributors

Jeen-Soo Bae†

†Authors have contributed equally to this work.