PDF(Pubmed)
Abstract：
Human DNA topoisomerase I (Topo I) is an essential enzyme in regulating DNA supercoiling during transcription and replication, and it is an important therapeutic target for anti-tumor agents. Bidens pilosa L. is a medicinal herb that is used as a folk medicine for cancers in China. A new flavonoid (1) and a new polyacetylene (20), along with eighteen flavonoids (2-19) and nine polyacetylenes (21-29), were isolated and identified from the methanol extract of the whole plant of B. pilosa, and some of the compounds (4, 5, 6 and 7) exhibited potent cytotoxicity against a panel of five human cancer cell lines. The DNA relaxation assay revealed that some flavonoids and polyacetylenes exerted inhibitory activities on human DNA Topo I, among them compounds 1, 2, 5, 6, 7, 8, 15, 19, 20, 22, and 24 were the most active ones, with IC50 values of 393.5, 328.98, 145.57, 239.27, 224.38, 189.84, 89.91, 47.5, 301.32, 178.03, and 218.27 μM, respectively. The structure-activity analysis of flavonoids was performed according to the results from the Topo I inhibition assay. The DNA content analysis revealed that 5, 6, and 7 potently arrested cell cycle at the G1/S and G2/M phases in human colon cancer cell DLD-1 depending on the concentration of the inhibitors. The levels of protein expression related to the G1/S and G2/M cell cycle checkpoints were in accordance with the results from the DNA content analysis. These findings suggest that flavonoids are one of the key active ingredients accounting for the anti-tumor effect of B. pilosa.
摘要：
人类DNA拓扑异构酶I（TopoI）是转录和复制过程中调节DNA超螺旋的必需酶，是抗肿瘤药物的重要治疗靶点。BidenspilosaL.是一种草药，在中国被用作治疗癌症的民间药物。一种新的类黄酮（1）和一种新的聚乙炔（20），连同18个类黄酮（2-19）和9个聚乙炔（21-29），从毛囊完整植物的甲醇提取物中分离和鉴定，和一些化合物(4、5、6和7)对一组五种人类癌细胞系表现出有效的细胞毒性。DNA弛豫分析表明，某些类黄酮和聚乙炔对人DNATopoI具有抑制活性，其中化合物1、2、5、6、7、8、15、19、20、22和24活性最强，IC50值为393.5、328.98、145.57、239.27、224.38、189.84、89.91、47.5、301.32、178.03和218.27μM，分别。根据TopoI抑制测定的结果进行类黄酮的结构-活性分析。DNA含量分析表明，根据抑制剂的浓度，5、6和7在人结肠癌细胞DLD-1中有效地将细胞周期阻滞在G1/S和G2/M期。与G1/S和G2/M细胞周期检查点相关的蛋白质表达水平与DNA含量分析的结果一致。这些发现表明黄酮类化合物是导致毛囊芽孢杆菌抗肿瘤作用的关键活性成分之一。
