鱼腥草中分离得到的咖啡酸和槲皮苷可抑制 DNA 拓扑异构酶 I 活性。

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

机构信息

School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.

出版信息

Nat Prod Res. 2011 Feb;25(3):222-31. doi: 10.1080/14786410903339044.

DOI:10.1080/14786410903339044

PMID:20544499

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.

摘要

鱼腥草甲醇提取物对哺乳动物 DNA 拓扑异构酶 I 具有抑制作用。两种拓扑异构酶 I 抑制化合物被分离并鉴定为咖啡酸和槲皮苷。咖啡酸和槲皮苷对拓扑异构酶 I 的抑制活性的 IC50 值分别约为 0.15 和 0.05 mM。45 µM 浓度的咖啡酸可引起人白血病 U937 细胞 50%的生长抑制，但对正常成纤维细胞 NIH3T3 细胞无作用。然而，槲皮苷却出人意料地刺激了 U937 和 NIH3T3 细胞的增殖。咖啡酸诱导的细胞死亡伴随着聚（ADP-核糖）聚合酶和 procaspase-3 的切割，表明这种抑制剂引发了细胞凋亡。使用流式细胞术分析也证实了咖啡酸的诱导凋亡作用。因为 DNA 拓扑异构酶 I 是肿瘤化疗的重要靶点，所以本研究表明，咖啡酸而不是槲皮苷可能通过抑制细胞拓扑异构酶 I 活性来抑制致癌疾病。