Inhibition of DNA Topoisomerase Ι by Flavonoids and Polyacetylenes Isolated from L.

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. L. is a medicinal herb that is used as a folk medicine for cancers in China. A new flavonoid () and a new polyacetylene (), along with eighteen flavonoids (-) and nine polyacetylenes (-), were isolated and identified from the methanol extract of the whole plant of , and some of the compounds (, , and ) 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 , , , , , , , , , , and were the most active ones, with IC 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 , , and potently arrested cell cycle at the G/S and G/M phases in human colon cancer cell DLD-1 depending on the concentration of the inhibitors. The levels of protein expression related to the G/S and G/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 .