Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
J Inorg Biochem. 2018 Feb;179:107-120. doi: 10.1016/j.jinorgbio.2017.11.004. Epub 2017 Nov 8.
The antiproliferative activity of the gold complex [Au(tpp)Cl] (1) (tpp=triphenyphosphine) against human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblast cells (MRC-5) was investigated. The compound exhibits stronger activity against MCF-7 cells than cisplatin. The apoptotic pathway, especially though the mitochondrion damage was concluded by cell cycle arrest, flow cytometry using Annexin V-Fluorescein IsoThioCyanate (FITC) and Propidium Iodide (PI) as indicators, assays and permeabilization of the mitochondrial membrane tests. The molecular mechanism of action of 1 was further studied by: (i) its catalytic activity on the oxidation of linoleic acid (an acid that partakes in membrane fluidity) to hyperoxolinoleic acid by oxygen and (ii) its binding affinity towards the calf thymus (CT) DNA. Since the deactivation of cisplatin by glutathione (GSH), is related with the development of cell resistance, the reaction of 1 with GSH was investigated by UV absorption spectroscopy. The absence of micronucleus in cells confirms that the complex has no in vitro toxicity. The in vivo genotoxicity caused by 1 was evaluated by Allium cepa test.
研究了金配合物[Au(tpp)Cl]（1）（tpp=三苯基膦）对人乳腺癌腺癌细胞（MCF-7）和正常人胎儿肺成纤维细胞（MRC-5）的抗增殖活性。该化合物对 MCF-7 细胞的活性比顺铂更强。通过细胞周期阻滞、使用 Annexin V-Fluorescein IsoThioCyanate（FITC）和碘化丙啶（PI）作为指示剂的流式细胞术、线粒体膜通透性试验，推断出凋亡途径主要通过线粒体损伤。通过以下方式进一步研究了 1 的作用机制：（i）其对氧氧化亚油酸（参与膜流动性的酸）生成过氧亚油酸的催化活性；（ii）其与小牛胸腺（CT）DNA 的结合亲和力。由于谷胱甘肽（GSH）使顺铂失活与细胞耐药性的发展有关，因此通过紫外吸收光谱研究了 1 与 GSH 的反应。细胞中无微核证实该配合物无体外毒性。通过洋葱测试评估了 1 在体内引起的遗传毒性。
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