The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)]2+
The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)]2+
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DOI：
10.1016/j.jinorgbio.2015.12.016
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发表时间：
2016-03-01
影响因子：
3.9
通讯作者：
Chen, Jin-can
中科院分区：
文献类型：
--
作者：
Chen, Lan-mei;Peng, Fa;Chen, Jin-can
合成并表征了一种新的钌甲基咪唑配合物[Ru（MeIm）（4）（p-cpip）]（2+）（Rul，p-cpip = 2-（4-氯苯基）-1H-咪唑并[4，5-f][1，10]菲咯啉，MeIm = 1-甲基咪唑）。采用电感耦合等离子体质谱（ICP-MS）、MTT法、流式细胞仪、彗星试验、倒置荧光显微镜和Western印迹等实验技术，对钌配合物的细胞摄取、体外细胞毒性、细胞周期阻滞和诱导凋亡机制进行了研究。值得注意的是，与顺铂相比，Rul对肺癌A549细胞显示出相对高的细胞毒活性，并且在肿瘤和正常细胞之间具有高选择性。进一步的研究表明，Rul可使细胞周期阻滞于G 0/G1期，并通过线粒体途径诱导细胞凋亡，这一途径涉及活性氧（ROS）积累、线粒体功能障碍以及Bcl-2和caspase相关家族成员的激活。为了提供更多关于可能的抗肿瘤机制的信息，还通过不同的分光光度法、热变性和粘度测量研究了体外DNA结合。(C)2016 Elsevier Inc. All rights reserved.
A new ruthenium methylimidazole complex [Ru(MeIm)(4)(p-cpip)](2+) (Rul, p-cpip = 2-(4-chlorophenyl)-1 H-imidazo[4,5-f][1,10]phenanthroline, MeIm = 1-methylimidazole) has been synthesized and characterized. The cellular uptake, in vitro cytotoxicities, cell cycle arrest and apoptosis-inducing mechanism of this Ru(II) complex have been extensively explored by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, Comet assay, inverted fluorescence microscope as well as Western blotting experimental techniques. Notably, Rul displayed relatively high cytotoxic activity against lung cancer A549 cells and had high selectivity between tumor and normal cells in comparison with cisplatin. Further studies showed that Rul caused cell cycle arrest at G0/G1 phase and induced apoptosis via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and Bcl-2 and caspase correlative family member activation. For providing more information about the possible antitumor mechanism, the in vitro DNA binding studies have been also investigated by different spectrophotometric methods, thermal denaturation and viscosity measurements. (C) 2016 Elsevier Inc. All rights reserved.