Luna Arthur Cássio de Lima, Santos Filho José Roberto de Assis, Hesse Henrique, Neto Salvador Claro, Chierice Gilberto Orivaldo, Maria Durvanei Augusto
Biochemistry and Biophysical Laboratory, Butantan Institute, 1500, Vital Brasil Avenue, Sao Paulo, 05503-900, Brazil.
Department of Medical Sciences, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
BMC Res Notes. 2018 Feb 14;11(1):126. doi: 10.1186/s13104-018-3170-7.
We aimed to evaluate the potential of DODAC/PHO-S liposomes on the modulation of the expression of pro-apoptotic proteins, loss of lysosomal integrity and the mitochondrial electrical potential, compared with phosphoethanolamine.
The results of this study demonstrate that DODAC/PHO-S liposomes have exhibited broad cytotoxic potential in B16F10 murine melanoma cells, with significantly greater proportions than treatment with PHO-S. The treatment with the DODAC/PHO-S 2.0 mM liposomal formulation was more efficient in decreasing mitochondrial electrical potential at the same concentrations and treatment time than PHO-S The liposomal formulation DODAC/PHO-S (2.0 mM) was more efficient to promote morphological changes in the cells, without presenting intact lysosomes, at the same time of treatment and concentration as PHO-S Our results demonstrated that the liposomal formulation increased DR4 receptor expression and activated caspases 8 and 3, resulting in the release of cytochrome c in B16F10 tumour cells, when compared to treatment with PHO-S The data obtained prove that the use of DODAC as carrier can maximize the cytotoxic effects of PHO-S This was demonstrated by the translocation of cytochrome c to the cytoplasm and activation of caspase-3 and 8, decreasing the mitochondrial electrical potential and generating morphological changes, in B16F10 cells.
我们旨在评估与磷酸乙醇胺相比，二癸基二甲基氯化铵/磷脂酰丝氨酸（DODAC/PHO-S）脂质体在调节促凋亡蛋白表达、溶酶体完整性丧失和线粒体膜电位方面的潜力。
本研究结果表明，DODAC/PHO-S脂质体在B16F10小鼠黑色素瘤细胞中表现出广泛的细胞毒性潜力，其比例显著高于磷酸乙醇胺（PHO-S）处理组。在相同浓度和处理时间下，2.0 mM的DODAC/PHO-S脂质体制剂在降低线粒体膜电位方面比PHO-S更有效。在与PHO-S相同的处理时间和浓度下，DODAC/PHO-S（2.0 mM）脂质体制剂在促进细胞形态变化方面更有效，且不存在完整的溶酶体。我们的结果表明，与PHO-S处理相比，脂质体制剂增加了DR4受体的表达并激活了半胱天冬酶8和3，导致B16F10肿瘤细胞中细胞色素c的释放。获得的数据证明，使用DODAC作为载体可以最大限度地提高PHO-S的细胞毒性作用。这在B16F10细胞中表现为细胞色素c易位至细胞质、半胱天冬酶-3和8的激活、线粒体膜电位降低以及产生形态变化。
