title: Direct electric current treatment modifies mitochondrial function and lipid body content in the A549 cancer cell line.
abstract: 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.
authors.affiliation: Laboratory of Multidisciplinary Pharmaceutical Sciences, College of Pharmacy, Center of Health Sciences (CCS), Federal University do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: cholandino@gmail.com.
authors.forename: Carla
authors.initials: C
authors.lastname: Holandino
authors.affiliation: Laboratory of Multidisciplinary Pharmaceutical Sciences, College of Pharmacy, Center of Health Sciences (CCS), Federal University do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Cesar Augusto Antunes
authors.initials: CA
authors.lastname: Teixeira
authors.affiliation: Laboratory of Multidisciplinary Pharmaceutical Sciences, College of Pharmacy, Center of Health Sciences (CCS), Federal University do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Felipe Alves Gomes
authors.initials: FA
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Multidisciplinary Pharmaceutical Sciences, College of Pharmacy, Center of Health Sciences (CCS), Federal University do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gleyce Moreno
authors.initials: GM
authors.lastname: Barbosa
authors.affiliation: Federal Institute of Education, Science and Technology of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Camila Monteiro
authors.initials: CM
authors.lastname: Siqueira
authors.affiliation: Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry, CCS, Federal University do Rio de Janeiro, Brazil.
authors.forename: Douglas Jardim
authors.initials: DJ
authors.lastname: Messeder
authors.affiliation: Laboratory of Multidisciplinary Pharmaceutical Sciences, College of Pharmacy, Center of Health Sciences (CCS), Federal University do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernanda Silva
authors.initials: FS
authors.lastname: de Aguiar
authors.affiliation: Laboratory of Electron Microscopy, Institute of Microbiology Prof. Paulo de Góes (IMPPG), CCS, UFRJ, Rio de Janeiro, Brazil.
authors.forename: Venicio Feo
authors.initials: VF
authors.lastname: da Veiga
authors.affiliation: Laboratory of Cellular Ultrastructure Hertha Meyer, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Wendell
authors.initials: W
authors.lastname: Girard-Dias
authors.affiliation: Laboratory of Cellular Ultrastructure Hertha Meyer, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Kildare
authors.initials: K
authors.lastname: Miranda
authors.affiliation: Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry, CCS, Federal University do Rio de Janeiro, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galina
authors.affiliation: Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcia Alves Marques
authors.initials: MA
authors.lastname: Capella
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcelo Marcos
authors.initials: MM
authors.lastname: Morales
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004599:Electric Stimulation Therapy; D004566:Electrodes; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000473:pathology*
chemical_list: D053148:Caspase 3
keywords: A549 human lung cancer; Anodic flow; Apoptosis; Direct electric current; Lipid bodies; Oxidative phosphorylation