Pennogenyl saponins induce cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells
Pennogenyl saponins induce cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells
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DOI：
10.1016/j.jep.2014.12.065
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发表时间：
2015-03-13
影响因子：
5.4
通讯作者：
Du, Jun-Rong
中科院分区：
文献类型：
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作者：
Long, Fang-Yi;Chen, Ya-Shu;Du, Jun-Rong
民族药理学相关性：偏诺皂苷是Paraphylaxis的特征性成分，在体外培养的细胞或动物模型中被报道具有诱导细胞凋亡或抗转移的抗癌活性。本研究的目的是评估四种偏诺皂苷（PS1-PS4）对一组人类癌症和正常细胞系的抗癌特性，并探索甾体皂苷在癌细胞中选择性抗癌作用的潜在机制。材料和方法：采用MTT法检测偏诺皂苷对人癌细胞株的抗癌活性差异（HepG 2肝细胞癌细胞、UACC-257黑色素瘤细胞、MCF-7乳腺癌和PC-3前列腺癌细胞）和正常人细胞系（L-02肝细胞和HEK 293肾细胞）。采用流式细胞术、JC-1染色和western blot分析等方法，检测了抗肿瘤偏诺皂苷对HepG 2、MCF-7和PC-3细胞凋亡、细胞周期和信号通路中主要效应子表达和/或激活的影响。PSI和PS2可显著诱导HepG 2细胞凋亡和细胞周期G2/M期阻滞，这至少与激活线粒体caspase依赖和非依赖的凋亡级联反应，抑制细胞周期蛋白依赖性激酶1和PI 3 K/Akt信号通路，调节丝裂原活化蛋白激酶有关。PSI和PS2对乳腺癌、肝癌和前列腺癌细胞具有较强的选择性抗癌活性。此外，PSI和PS2的抗癌作用与诱导HepG 2细胞凋亡和通过多个靶点阻断细胞周期进程有关。这些发现表明PSI和PS2可以被认为是用于治疗某些癌症如肝癌的潜在药剂。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Pennogenyl saponins, the characterized components of Rhizoma Paridis, have been reported to have anticancer activity through induction of apoptosis or anti-metastasis in cultured cells or animal models. The aim of the study was to evaluate the anticancer properties of four pennogenyl saponins (PS1-PS4) on a panel of human cancer and normal cell lines, and explore the potential mechanisms underlying the selective anticancer effects of the steroidal saponins in cancer cells.Materials and methods: Differences in the anticancer activity of pennogenyl saponins were examined by MTT assay in human cancer cell lines (HepG2 hepatocellular carcinoma cells, UACC-257 melanoma cells, MCF-7 breast and PC-3 prostate cancer cells) and normal human cell lines (L-02 liver cells and HEK293 kidney cells). Flow cytometry analysis, JC-1 staining and western blot analysis were applied to detect the effects of anticancer pennogenyl saponins on apoptosis, cell cycle, and expression and/or activation of main effectors involved in the potential signaling pathways.Results: Among the tested four saponins, only PSI and PS2 selectively inhibited cell growth in HepG2, MCF-7 and PC-3 cells. Moreover, PSI and PS2 could significantly induce apoptosis and cell cycle G2/M arrest in HepG2 cells, which were at least associated with activation of mitochondrial caspase-dependent and -independent apoptotic cascades, inhibition of cyclin-dependent kinase 1 and PI3K/Akt signaling pathway, and modulation of mitogen-activated protein kinases.Conclusions: PSI and PS2 had potent and selective anticancer activity to breast, liver and prostate cancer cells. Furthermore, the anticancer effects of PSI and PS2 were associated with induction of apoptosis and blockage of cell cycle progression through multiple targets in HepG2 cells. These findings suggest that PSI and PS2 can be considered as potential agents for the treatment of some cancers such as hepatoma. (C) 2015 Elsevier Ireland Ltd. All rights reserved.