Ginsenoside Rd from Panax notoginseng is cytotoxic towards HeLa cancer cells and induces apoptosis

Ginsenoside Rd from Panax notoginseng is cytotoxic towards HeLa cancer cells and induces apoptosis
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DOI:
10.1002/cbdv.200690022
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发表时间:
2006-01-01
影响因子:
2.9
通讯作者:
Ye, YP
Ye, YP
中科院分区:
化学3区
文献类型:
--
作者:
Yang, ZG;Sun, HX;Ye, YP

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从三七中分离得到的皂苷化合物三七皂苷Rd(1)用于治疗心血管疾病、炎症、各种身体疼痛、创伤以及由损伤引起的内外出血。在这项研究中,我们报告说,我抑制人宫颈癌(HeLa)细胞的细胞生长的浓度和时间依赖性的方式,与IC 50值为150.5 +/- 0.8 μ g/ml孵育48小时后。琼脂糖凝胶电泳显示,药物处理的细胞表现出凋亡的特征,包括典型的形态学特征和DNA梯状条带的形成。流式细胞仪分析表明,HeLa细胞暴露于1的细胞周期分布的特征是G(0)/G(1)期细胞减少和S期细胞增加,分别以剂量依赖性的方式。210 μ g/ml的1处理HeLa细胞48 h,凋亡率为35.8%。此外,发现1分别增加Bax蛋白的表达和降低Bcl-2蛋白的表达,并降低HeLa细胞的线粒体跨膜电位。半胱天冬酶-3抑制剂DEVD-CHO(2 μ M)增加了用1.综上所述,我们的研究表明,Bcl-Rd(1)通过下调Bcl-2的表达,上调Bax的表达,降低线粒体跨膜电位,激活caspase-3通路,显著抑制HeLa细胞增殖,并诱导细胞凋亡。因此,我可以作为开发新的抗宫颈癌的化学治疗或化学预防药物的先导。
The saponin ginsenoside Rd (1), isolated from Panax notoginseng, is used for the treatment of cardiovascular diseases, inflammation, different body pains, trauma, and internal and external bleeding due to injury. In this study, we report that I inhibits the cell growth of human cervical cancer (HeLa) cells in a concentration- and time-dependent manner, with an IC50 value of 150.5 +/- 0.8 mu g/ml after 48 h of incubation. The drug-treated cells displayed features of apoptosis, including typical morphological characteristics and formation of DNA ladders, as evident from agarose-gel electrophoresis. Flow-cytometric analysis showed that the cell-cycle distribution of HeLa cells exposed to 1 is characterized by a decrease of the G(0)/G(1)-phase and an increase of the S-phase cells, respectively, in a dose-dependent manner. The apoptotic rate of HeLa cells treated for 48 h with 210 mu g/ml of 1 was 35.8%. Further, 1 was found to increase the expression of Bax and to decrease the expression of Bcl-2 proteins, respectively, and to lower the mitochondrial transmembrane potential of HeLa cells. The caspase-3 inhibitor DEVD-CHO (at 2 mu M) increased the viability of HeLa cells treated with 1. Taken together, our study suggests that ginsenoside Rd (1) significantly inhibits HeLa cell proliferation, and induces cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering the mitochondrial transmembrane potential, and activating the caspase-3 pathways Thus, I could serve as a lead to develop novel chemotherapeutic or chemopreventive agents against human cervical cancer.