The effects and mechanism of peiminine-induced apoptosis in human hepatocellular carcinoma HepG2 cells
The effects and mechanism of peiminine-induced apoptosis in human hepatocellular carcinoma HepG2 cells
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DOI：
10.1371/journal.pone.0201864
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发表时间：
2019-01-07
期刊：
影响因子：
3.7
通讯作者：
Zhao, Jiarong
中科院分区：
文献类型：
--
作者：
Chao, Xu;Wang, Guoquan;Zhao, Jiarong
Peiminine 是从 Bolbostemma paniculatum (Maxim) Franquet（葫芦科）中分离出来的化合物，具有抗肿瘤活性。但其抗肿瘤活性的精确分子机制仍然难以捉摸。本研究旨在探讨贝胺碱诱导人肝癌细胞凋亡及其分子机制。采用MTT法评估贝胺碱对Hela、HepG2、SW480和MCF-7细胞系的抗癌作用。核染色和流式细胞术检测贝胺碱诱导的细胞凋亡。通过线粒体膜电位评估和蛋白质印迹分析来研究贝胺碱诱导细胞凋亡的机制。结果显示，贝胺碱以时间和剂量依赖性方式降低HepG2细胞的活力，24小时时的IC50为4.58μg/mL。 Peiminine 显着增加 HepG2 细胞中凋亡细胞的百分比和线粒体膜电位，呈剂量依赖性。 Western blotting结果显示，贝胺碱处理后的HepG2细胞中Bcl-2、procaspase-3、procaspase-8、procaspase-9和PARP的表达减少，而Box、caspase-3、caspase-8、caspase-9和cleaved PARP(1)的表达增加。结果表明，贝胺碱可通过外源性和内源性凋亡途径诱导人肝癌HepG2细胞发生凋亡。
Peiminine is a compound isolated from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), which has demonstrated antitumor activities. But its precise molecular mechanism underlying antitumor activity remain elusive. In this study, peiminine-induced apoptosis towards human hepatocellular carcinoma and its molecular mechanism were investigated. MTT assay was employed to assess anticancer effects of peiminine upon Hela, HepG2, SW480 and MCF-7 cell lines. Nuclear staining and flow cytometry were carried out to detect apoptosis induced by peiminine. Mitochondrial membrane potential evaluation and Western blot analysis were performed to investigate the mechanism of peiminine-induced apoptosis. The results showed peiminine reduced the viability of HepG2 cells in a time- and dose-dependent manner and had an IC50 of 4.58 mu g/mL at 24h. Peiminine significantly increased the percentage of apoptotic cells and the mitochondrial membrane potential dose-dependently in HepG2 cells. The results of Western blotting indicated the expressions of Bcl-2, procaspase-3, procaspase-8, procaspase-9, and PARP decreased in HepG2 cells treated with peiminine, while the expressions of Box, caspase-3, caspase-8, caspase-9, and cleaved PARP(1) increased. The result suggests that peiminine can induce apoptosis in human hepatocellular carcinoma HepG2 cells through both extrinsic and intrinsic apoptotic pathways.