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首页> 外文期刊>FEBS Open Bio >The cytotoxicity of BAMLET complexes is due to oleic acid and independent of the @a-lactalbumin component
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The cytotoxicity of BAMLET complexes is due to oleic acid and independent of the @a-lactalbumin component

机译：BAMLET复合物的细胞毒性是由于油酸引起的，与@ a-乳白蛋白成分无关

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摘要

Lipid-protein complexes comprised of oleic acid (OA) non-covalently coupled to human/bovine @a-lactalbumin, named HAMLET/BAMLET, display cytotoxic properties against cancer cells. However, there is still a substantial debate about the role of the protein in these complexes. To shed light into this, we obtained three different BAMLET complexes using varying synthesis conditions. Our data suggest that to form active BAMLET particles, OA has to reach critical micelle concentration with an approximate diameter of 250nm. Proteolysis experiments on BAMLET show that OA protects the protein and is probably located on the surface, consistent with a micelle-like structure. Native or unfolded @a-lactalbumin without OA lacked any tumoricidal activity. In contrast, OA alone killed cancer cells with the same efficiency at equimolar concentrations as its formulation as BAMLET. Our data show unequivocally that the cytotoxicity of the BAMLET complex is exclusively due to OA and that OA alone, when formulated as a micelle, is as toxic as the BAMLET complex. The contradictory literature results on the cytotoxicity of BAMLET might be explained by our finding that it was imperative to sonicate the samples to obtain toxic OA.
机译：由非共价偶联于人/牛@ a-乳白蛋白的油酸（OA）组成的脂蛋白复合物，被称为HAMLET / BAMLET，对癌细胞具有细胞毒性。但是，关于蛋白质在这些复合物中的作用仍存在大量争论。为了阐明这一点，我们使用不同的合成条件获得了三种不同的BAMLET配合物。我们的数据表明，要形成活性BAMLET颗粒，OA必须达到约250nm直径的临界胶束浓度。在BAMLET上进行的蛋白水解实验表明，OA保护该蛋白质，并且可能位于表面，与胶束样结构一致。没有OA的天然或未折叠的@ a-乳白蛋白缺乏任何杀肿瘤活性。相比之下，单独的OA在等摩尔浓度下以与BAMLET相同的浓度杀死癌细胞。我们的数据明确表明，BAMLET复合物的细胞毒性完全归因于OA，而单独的OA配制成胶束时，其毒性与BAMLET复合物一样。关于BAMLET的细胞毒性的相反文献结果可能由我们的发现所解释，即必须对样品进行超声处理以获得有毒的OA。

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