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.
A chloroform extract of the edible mushroom Pleurotus eryngii showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as ubiquinone-9. Ubiquinone-9 was shown to inhibit the activity of topoisomerase I with IC(50) of about 50 microM. Concentration of 110 microM ubiquinone-9 caused 50% growth inhibition of human leukaemia U937 cells, but not that of normal fibroblast NIH3T3 and 3Y1 cells. Ubiquinone-9-induced cell death was characterised with the cleavage of poly (ADP-ribose) polymerase and pro-caspase 3. Furthermore, ubiquinone-9 induced the fragmentation of DNA into an apoptotic DNA ladder, indicating that the inhibitor triggered apoptosis. The induction of apoptosis by ubiquinone-9 was also confirmed using flow cytometry analysis. Taken together, these results suggest that ubiquinone-9 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.
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