Holandino Carla, Teixeira Cesar Augusto Antunes, de Oliveira Felipe Alves Gomes, Barbosa Gleyce Moreno, Siqueira Camila Monteiro, Messeder Douglas Jardim, de Aguiar Fernanda Silva, da Veiga Venicio Feo, Girard-Dias Wendell, Miranda Kildare, Galina Antonio, Capella Marcia Alves Marques, Morales Marcelo Marcos
Laboratory of Multidisciplinary Pharmaceutical Sciences, College of Pharmacy, Center of Health Sciences (CCS), Federal University do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Multidisciplinary Pharmaceutical Sciences, College of Pharmacy, Center of Health Sciences (CCS), Federal University do Rio de Janeiro, Rio de Janeiro, Brazil.
Bioelectrochemistry. 2016 Oct;111:83-92. doi: 10.1016/j.bioelechem.2016.05.004. Epub 2016 May 11.
Electrochemical therapy (EChT) entails treatment of solid tumors with direct electric current (DC). This work evaluated the specific effects of anodic flow generated by DC on biochemical and metabolic features of the A549 human lung cancer cell line. Apoptosis was evaluated on the basis of caspase-3 activity and mitochondrial transmembrane potential dissipation. Cell morphology was analyzed using transmission electron microscopy, and lipid droplets were studied through morphometric analysis and X-ray qualitative elemental microanalysis. High-resolution respirometry was used to assess mitochondrial respiratory parameters. Results indicated A549 viability decreased in a dose-dependent manner with a prominent drop between 18 and 24h after treatment (p<0.001), together with a two-fold increase in caspase-3 activity. AF-treatment induced a significantly increase (p<0.01) in the cell number with disrupted mitochondrial transmembrane potential. Furthermore, treated cells demonstrated important ultrastructural mitochondria damage and a three-fold increase in the cytoplasmic lipid bodies' number, quantified by morphometrical analyses. Conversely, 24h after treatment, the cells presented a two-fold increase of residual oxygen consumption, accounting for 45.3% of basal oxygen consumption. These results show remarkable alterations promoted by anodic flow on human lung cancer cells which are possibly involved with the antitumoral effects of EChT.
电化学疗法(EChT)需要用直流电(DC)治疗实体瘤。这项工作评估了直流电产生的阳极流对A549人肺癌细胞系生化和代谢特征的具体影响。基于半胱天冬酶-3活性和线粒体跨膜电位耗散评估细胞凋亡。使用透射电子显微镜分析细胞形态,并通过形态计量分析和X射线定性元素微分析研究脂滴。使用高分辨率呼吸测定法评估线粒体呼吸参数。结果表明,A549细胞活力以剂量依赖性方式降低,在治疗后18至24小时之间显著下降(p<0.001),同时半胱天冬酶-3活性增加两倍。阳极流处理导致线粒体跨膜电位破坏的细胞数量显著增加(p<0.01)。此外,经处理的细胞表现出线粒体重要的超微结构损伤,通过形态计量分析定量,细胞质脂质体数量增加了三倍。相反,治疗后24小时,细胞的残余氧消耗量增加了两倍,占基础氧消耗量的45.3%。这些结果表明阳极流对人肺癌细胞有显著影响,这可能与电化学疗法的抗肿瘤作用有关。