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Label-free quantitative proteomics of the MCF-7 cellular response to a ferritin-metallodrug complex.
Molecular Omics ( IF 3.0 ) Pub Date : 2020-02-04 , DOI: 10.1039/c9mo00158a
Gabriella Pinto 1 , Mariavittoria D'Acierno , Anna Illiano , Ganna Petruk , Giarita Ferraro , Antonello Merlino , Daria Maria Monti , Jasminka Godovac-Zimmermann , Angela Amoresano
Affiliation  

Auoxo3 is a gold(iii) compound endowed with cytotoxic activity towards a variety of malignant cells. Encapsulation of Auoxo3 within horse spleen ferritin (Ft) improves the selectivity of the gold compound towards cancer cells over normal cells. In the current work, the changes in protein expression are presented in response to MCF-7 stimulation with Auoxo3-encapsulated Ft versus the free Au(iii) compound by a label-free proteomics approach. A 159-protein dataset showed significant changes between the stimulations with Auoxo3 and Auoxo3-encapsulated Ft, suggesting that this cellular perturbation caused the alteration of different cellular processes. In detail, roughly 30% of proteins were downregulated mainly in the spliceosome complex (U2AF1, SF3B2, PRPF4, SNSRP200, EFTUD2, PRPF6, and PRPF8) in agreement with the cytostatic effect observed during cellular growth. Another 30% of proteins were upregulated primarily in glutathione biosynthesis, suggesting an alteration of the redox potential, as validated by Western blot analyses. To the best of our knowledge, this work represents the first large scale proteomics study on the effects of a gold-based drug encapsulated within the Ft nanocage on cancer cells.

中文翻译:

MCF-7细胞对铁蛋白-金属药物复合物的无标记定量蛋白质组学。

Auoxo3是一种金(iii)化合物,对多种恶性细胞具有细胞毒活性。Auoxo3在马脾铁蛋白(Ft)中的封装提高了金化合物对癌细胞的选择性,超过了正常细胞。在当前的工作中,蛋白表达的变化是通过无标记蛋白质组学方法响应于用Auoxo3包裹的Ft相对于游离Au(iii)化合物对MCF-7刺激而提出的。159个蛋白质的数据集显示在用Auoxo3和包被Auoxo3的Ft刺激之间存在显着变化,表明这种细胞扰动引起了不同细胞过程的改变。详细而言,大约30%的蛋白质主要在剪接体复合物中被下调(U2AF1,SF3B2,PRPF4,SNSRP200,EFTUD2,PRPF6,和PRPF8)与细胞生长期间观察到的细胞抑制作用一致。蛋白质印迹分析证实,另外30%的蛋白质主要在谷胱甘肽的生物合成中被上调,表明氧化还原电位发生了变化。据我们所知,这项工作代表了首次大规模蛋白质组学研究,研究的是Ft纳米笼中封装的金基药物对癌细胞的影响。
更新日期:2020-01-17
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