College of Pharmacy, Dalian Medical University, 9 Western Lvshun South Road, Dalian, 116044, China.
Cytotechnology. 2014 Jan;66(1):37-50. doi: 10.1007/s10616-013-9534-x. Epub 2013 Feb 9.
Zuojinwan (ZJW), a famous Chinese medicinal formula, contains two medicinal herbs Coptis chinese Frach and Evodia rutaecarpa (Juss.) Benth in the ratio of 6: 1. The inhibitory effects of ZJW on eight kinds of human cancer cell lines including SMMC-7721, BEL-7402, BEL-7404, HepG2, A549, NCI-H446, NCI-H460 and HCT- 116 cells were evaluated, and the possible mechanism was investigated. The growths of the eight kinds of cancer cells were inhibited by ZJW assessed through MTT assay. Flow cytometry assay revealed a sub-G1 peak with reduced DNA content was formed. The cell cycle was arrested in the G0/G1 phase in ZJW-treated SMMC-7721 and HepG2 cells, and in the S phase for NCI-H460 cells. Significant DNA damage was produced by ZJW assessed with single-cell gel electrophoresis assay. Morphological changes were also observed. Caspase-3 and -9 activities were increased following ZJW treatment. Western blot analysis showed that Bax and Bak protein levels were increased after ZJW treatment, while Bcl-2 and Bcl-xl protein levels were decreased. Our results suggest that ZJW has significant anti-cancer activities due to induction of mitochondria- dependent apoptosis pathway. Therefore, ZJW has the potential to be a novel chemotherapy drug to treat hepatoma, lung cancer and colon cancer by suppressing tumor growth.
左金丸(ZJW)是一种著名的中药方剂,由黄连和吴茱萸以 6:1 的比例组成。本研究评估了 ZJW 对 SMMC-7721、BEL-7402、BEL-7404、HepG2、A549、NCI-H446、NCI-H460 和 HCT-116 等 8 种人类癌细胞系的抑制作用,并探讨了其可能的作用机制。通过 MTT 法评估 ZJW 对 8 种癌细胞生长的抑制作用。流式细胞术检测显示形成了具有减少 DNA 含量的亚 G1 峰。ZJW 处理的 SMMC-7721 和 HepG2 细胞的细胞周期被阻滞在 G0/G1 期,NCI-H460 细胞被阻滞在 S 期。单细胞凝胶电泳试验评估了 ZJW 产生的明显的 DNA 损伤。还观察到形态学变化。Caspase-3 和 -9 活性在 ZJW 处理后增加。Western blot 分析表明,ZJW 处理后 Bax 和 Bak 蛋白水平增加,而 Bcl-2 和 Bcl-xl 蛋白水平降低。我们的研究结果表明,ZJW 通过诱导线粒体依赖性凋亡途径具有显著的抗癌活性。因此,ZJW 具有通过抑制肿瘤生长来治疗肝癌、肺癌和结肠癌的新型化疗药物的潜力。