Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
Eur J Pharmacol. 2010 Feb 10;627(1-3):33-41. doi: 10.1016/j.ejphar.2009.10.035. Epub 2009 Oct 24.
Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), a natural anthraquinone derivative isolated from Rheum palmatum L, has been reported to exhibit anti-cancer effect on several human cancers such as liver cancers and lung cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. Our preliminary study showed that emodin had highly cytotoxic effect on human chronic myeloid leukemia K562 cell lines. This study was performed to investigate the anti-tumor effect of emodin in human K562 cell line in vitro and in vivo. The MTT data showed the inhibition on growth of K562 cells following emodin treatment. Flow cytometry showed that the cell cycle of K562 cells was arrested in G(0)/G(1) phase. Through Western blot analysis, we found that the apoptosis-related protein Bcl-2 was decreased in a dose-dependent manner and the Bax was increased after emodin treatment. Moreover, activations of caspase-3, -8 and -9 were demonstrated in vitro and in vivo. The increased Bax concurrent with the decreased of Bcl-2 indicated that emodin treatment might result in apoptosis of K562 cells. The cell apoptosis was also directly demonstrated by Annexin V-FITC, and DNA fragmentation assay. Additionally, the tumoricidal effect of emodin was measured using a xenograft nude mice model. We found that, after inoculated with the K562 cells, the nude mice treated with emodin showed a significant decrease of tumor volume and tumor weight in comparison to the control. Emodin could cause the regression of tumor. Both in vitro and in vivo studies suggest that emodin can be developed as a promising anti-chronic myeloid leukemia drug.
大黄素(1,3,8-三羟基-6-甲基蒽醌)是从大黄中分离得到的天然蒽醌衍生物,已被报道对多种人类癌症具有抗癌作用,如肝癌和肺癌。然而,大黄素介导的肿瘤消退的分子机制尚未完全确定。我们的初步研究表明,大黄素对人慢性髓系白血病 K562 细胞系具有高度细胞毒性作用。本研究旨在探讨大黄素在体外和体内对人 K562 细胞系的抗肿瘤作用。MTT 数据显示大黄素处理后对 K562 细胞生长的抑制作用。流式细胞术显示 K562 细胞的细胞周期被阻滞在 G0/G1 期。通过 Western blot 分析,我们发现凋亡相关蛋白 Bcl-2 呈剂量依赖性降低,Bax 增加。此外,在体外和体内均证明了 caspase-3、-8 和 -9 的激活。Bax 的增加伴随着 Bcl-2 的减少表明大黄素处理可能导致 K562 细胞凋亡。细胞凋亡也通过 Annexin V-FITC 和 DNA 片段化检测直接证实。此外,还使用异种移植裸鼠模型测量了大黄素的杀瘤作用。我们发现,接种 K562 细胞后,与对照组相比,用大黄素治疗的裸鼠肿瘤体积和重量明显减少。大黄素可引起肿瘤消退。体内外研究均表明,大黄素可开发为一种有前途的抗慢性髓系白血病药物。