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绞股蓝总皂苷导致人舌鳞癌细胞 SAS 中 DNA 损伤,并抑制 DNA 修复基因的表达。

Gypenosides causes DNA damage and inhibits expression of DNA repair genes of human oral cancer SAS cells.

机构信息

School of Chinese Medicine, China Medical University, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan, R.O.C.

出版信息

In Vivo. 2010 May-Jun;24(3):287-91.

Abstract

Gypenosides (Gyp) are the major components of Gynostemma pentaphyllum Makino, a Chinese medical plant. Recently, Gyp has been shown to induce cell cycle arrest and apoptosis in many human cancer cell lines. However, there is no available information to address the effects of Gyp on DNA damage and DNA repair-associated gene expression in human oral cancer cells. Therefore, we investigated whether Gyp induced DNA damage and DNA repair gene expression in human oral cancer SAS cells. The results from flow cytometric assay indicated that Gyp-induced cytotoxic effects led to a decrease in the percentage of viable SAS cells. The results from comet assay revealed that the incubation of SAS cells with Gyp led to a longer DNA migration smear (comet tail) when compared with control and this effect was dose-dependent. The results from real-time PCR analysis indicated that treatment of SAS cells with 180 mug/ml of Gyp for 24 h led to a decrease in 14-3-3sigma, DNA-dependent serine/threonine protein kinase (DNAPK), p53, ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and breast cancer gene 1 (BRCA1) mRNA expression. These observations may explain the cell death caused by Gyp in SAS cells. Taken together, Gyp induced DNA damage and inhibited DNA repair-associated gene expressions in human oral cancer SAS cells in vitro.

摘要

绞股蓝皂苷(Gyp)是葫芦科绞股蓝属植物绞股蓝的主要成分。最近研究表明,绞股蓝苷能诱导多种人癌细胞系的细胞周期停滞和凋亡。然而,目前还没有关于绞股蓝苷对人口腔癌细胞 DNA 损伤和与 DNA 修复相关基因表达的影响的信息。因此,我们研究了绞股蓝苷是否能诱导人口腔癌细胞 SAS 中的 DNA 损伤和 DNA 修复基因的表达。流式细胞术检测结果表明,绞股蓝苷诱导的细胞毒性作用导致活 SAS 细胞的百分比降低。彗星试验结果显示,与对照组相比,SAS 细胞与绞股蓝苷孵育后,DNA 迁移的彗尾(彗星尾巴)更长,这种效应呈剂量依赖性。实时 PCR 分析结果表明,用 180μg/ml 的绞股蓝苷处理 SAS 细胞 24 小时,导致 14-3-3σ、DNA 依赖性丝氨酸/苏氨酸蛋白激酶(DNAPK)、p53、共济失调毛细血管扩张突变(ATM)、共济失调毛细血管扩张症和 Rad3 相关(ATR)和乳腺癌基因 1(BRCA1)mRNA 表达减少。这些观察结果可能解释了绞股蓝苷在 SAS 细胞中引起的细胞死亡。综上所述,绞股蓝苷在体外诱导人口腔癌细胞 SAS 中的 DNA 损伤,并抑制与 DNA 修复相关的基因表达。

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