Fu Xiao-yan, Zhang Shuai, Wang Kun, Yang Ming-feng, Fan Cun-dong, Sun Bao-liang
Department of Chemistry, Jinan University, Guangzhou, 510632, China.
School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China.
Cell Mol Neurobiol. 2015 Oct;35(7):953-9. doi: 10.1007/s10571-015-0190-x. Epub 2015 Apr 10.
Caudatin, one of the species of C-21 steroidal glycosides mainly isolated from the root of Cynanchum bungei Decne, exhibits potent anticancer activities. However, the mechanism remains poorly defined. In the present study, the growth inhibitory effect and mechanism of caudatin on human glioma cells were evaluated in vitro. The results revealed that caudatin time- and dose-dependently inhibited U251 and U87 cells growth. Flow cytometry analysis indicated that caudatin-induced growth inhibition against U251 and U87 cells was mainly achieved by the induction of G0/G1 and S-phase cell cycle arrest through triggering DNA damage, as convinced by the up-regulation of p53, p21, and histone phosphorylation, as well as the down-regulation of cyclin D1. Moreover, caudatin treatment also triggered the activation of ERK and inactivation of AKT pathway. LY294002 (an AKT inhibitor) addition enhanced caudation-induced AKT inhibition, indicating that caudatin inhibited U251 cells growth in an AKT-dependent manner. Taken together, these results indicate that caudatin may act as a novel cytostatic reagent against human glioma cells through the induction of DNA damage-mediated cell cycle arrest with the involvement of modulating MAPK and AKT pathways.
白薇醇是从白薇根中主要分离得到的C-21甾体苷类之一，具有强大的抗癌活性。然而，其作用机制仍不清楚。在本研究中，在体外评估了白薇醇对人胶质瘤细胞的生长抑制作用及其机制。结果显示，白薇醇对U251和U87细胞的生长抑制具有时间和剂量依赖性。流式细胞术分析表明，白薇醇诱导的对U251和U87细胞的生长抑制主要是通过触发DNA损伤诱导G0/G1期和S期细胞周期阻滞来实现的，这一点可通过p53、p21上调和组蛋白磷酸化以及细胞周期蛋白D1下调来证实。此外，白薇醇处理还触发了ERK的激活和AKT通路的失活。添加LY294002（一种AKT抑制剂）增强了白薇醇诱导的AKT抑制，表明白薇醇以AKT依赖的方式抑制U251细胞生长。综上所述，这些结果表明白薇醇可能通过诱导DNA损伤介导的细胞周期阻滞并涉及调节MAPK和AKT通路，作为一种新型的抗人胶质瘤细胞的细胞生长抑制剂。
