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首页> 外文期刊>RSC Advances >Modification of Rapana thomasiana hemocyanin with choline amino acid salts significantly enhances its antiproliferative activity against MCF-7 human breast cancer cells
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Modification of Rapana thomasiana hemocyanin with choline amino acid salts significantly enhances its antiproliferative activity against MCF-7 human breast cancer cells

机译：用胆碱氨基酸盐修饰Rapana thomasiana血蓝蛋白可显着增强其对MCF-7人乳腺癌细胞的抗增殖活性

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摘要

This is the first study on the interactions of ionic liquids with large metalloproteins, in particular hemocyanins (Hcs). At first, complexes of a Hc from Rapana thomasiana (RtH) with a series of biocompatible choline amino acid salts [Chol][AA] were obtained. Applying UV-vis spectroscopy, Fourier-transformed infrared spectroscopy and differential scanning calorimetry the effect of these organic salts on the structure and thermal stability of RtH was assessed. Then, the cytotoxic effect of RtH-[Chol][AA] on breast cancer cells (MCF-7) and 3T3 fibroblast cells (non cancerous) was evaluated. We found that all [Chol][AA] induced clear time- and concentration-dependent alterations in the RtH conformation. The conformation and the thermal stability of IL-modified RtH depend strongly on the type of the anion of the tested compounds. All [Chol][AA]-modified RtHs exhibited lower thermal stability than the native RtH. At the same time, we established a good correlation between the structure of RtH and its antitumor activity. Namely, RtH-[Chol][AA] complexes exhibited enhanced antiproliferative activity toward the MCF-7 cell line. The observed antiproliferative effect was cell specific and the compounds have no effect or in some cases have stimulatory effect on fibroblasts.
机译：这是关于离子液体与大型金属蛋白（尤其是血蓝蛋白（Hcs））相互作用的首次研究。首先，获得了来自Rapana thomasiana（RtH）的Hc与一系列生物相容性胆碱氨基酸盐[Chol] [AA]的复合物。应用紫外可见光谱，傅立叶变换红外光谱和差示扫描量热法，评估了这些有机盐对RtH的结构和热稳定性的影响。然后，评估了RtH- [Chol] [AA]对乳腺癌细胞（MCF-7）和3T3成纤维细胞（非癌细胞）的细胞毒性作用。我们发现，所有[Chol] [AA]均可诱导RtH构象发生明显的时间和浓度依赖性变化。 IL-修饰的RtH的构象和热稳定性在很大程度上取决于所测试化合物的阴离子类型。所有[Chol] [AA]修饰的RtHs均比天然RtH表现出较低的热稳定性。同时，我们在RtH的结构与其抗肿瘤活性之间建立了良好的相关性。即，RtH- [Chol] [AA]复合物表现出对MCF-7细胞系增强的抗增殖活性。观察到的抗增殖作用是细胞特异性的，该化合物对成纤维细胞无作用，或在某些情况下具有刺激作用。

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