Mirabijalone-B的抗肿瘤效应及对DNA拓扑异构酶的影响

Antitumor activity of compound Mirabijalone B and its effect on DNA topoisomerases

目的研究化合物Mirabijalone-B(MB)的抗肿瘤活性及对DNA拓扑异构酶(TOPO)活性的影响。方法以5株人肿瘤细胞株为模型,采用改良MTT法检测化合物MB的体外抗肿瘤活性;以质粒pBR322超螺旋DNA为底物,采用凝胶电泳分别检测MB对TOPOⅠ、Ⅱ介导的pBR322DNA解旋反应的影响。结果化合物MB对5株人肿瘤细胞株K562、HL-60、A549、Bel-7402和SGC-7901生长增殖的半数抑制浓度(IC50)分别为8.73、1.26、4.44、1.93和3.55mg.L-1;MB在80和16mg·mL-1浓度时,分别完全抑制TOPOⅠ、Ⅱ介导的pBR322超螺旋DNA的解旋反应;但在无TO-PO存在的条件下,MB对pBR322超螺旋DNA的解旋反应无直接影响。结论化合物MB体外明显抑制人肿瘤细胞的生长增殖,对DNATOPO尤其是TOPOⅡ活性的抑制可能是其抗肿瘤作用的机制之一。

Aim To investigate the antitumor effect of mirabijalone B （MB） isolated from Mirabilis jalapa L and its effect on DNA topoisomerases. Methods The cytotoxicity of MB on the five human tumor cell lines was detected by modified MTT assay in vitro. The effects of MB on topoisomerase （topo）-mediated pBR322 DNA relaxation and on pBR322 DNA relaxation in absence of TOPO were measured by using agarose gel electrophoresis. Results Compound MB showed an obvious cytotoxicity, the IC50 for five hmnan tumor cell lines--K562, HL-60, A549, Bel-7402 and SGC-7901 were 8.73, 1.26, 4.44,1.94 and 3.55 mg · L^-1 , respectively. At the Concentrations of 80 and 16 mg· L^-1, MB completely inhibited the pBR322 DNA relaxation mediated by TOPO I and TOPO Ⅱ , respectively, but it had no direct effect on pBR322 DNA relaxation in absence Of TOPO. Conclusions Compound MB has antitumor activity against human tumor cell lines in vitro, and the inhibitory effect of MB on DNA TOPO activity, especially on TOPO Ⅱ may be the one of its mechanisms of action.