10.1371/journal.pntd.0005805.g005 Janny A. Villa-Pulgarín Janny A. Villa-Pulgarín Consuelo Gajate Consuelo Gajate Javier Botet Javier Botet Alberto Jimenez Alberto Jimenez Nicole Justies Nicole Justies Rubén E. Varela-M Rubén E. Varela-M Álvaro Cuesta-Marbán Álvaro Cuesta-Marbán Ingrid Müller Ingrid Müller Manuel Modolell Manuel Modolell José L. Revuelta José L. Revuelta Faustino Mollinedo Faustino Mollinedo Involvement of mitochondria and ROS generation in edelfosine-induced cell death in <i>Leishmania</i> parasites and cancer cells. Public Library of Science 2017 ATP synthase lipid raft-located F O F 1 F O F 1 ATP synthase inhibition Saccharomyces cerevisiae yeast APL tumor cells tumor cell apoptosis-inducer edelfosine edelfosine drug resistance Leishmania axenic amastigotes ether lipid edelfosine Background Leishmaniasis DNA novel druggable targets Leishmania parasites raft-located F O F 1 vivo antileishmanial activity tumor cell mitochondria edelfosine-induced cell death intracellular Leishmania amastigotes show antileishmanial activity macrophage pro-inflammatory responses 2017-08-22 17:26:14 Figure https://plos.figshare.com/articles/figure/Involvement_of_mitochondria_and_ROS_generation_in_edelfosine-induced_cell_death_in_i_Leishmania_i_parasites_and_cancer_cells_/5332339 <p>(<b>A</b>) <i>L</i>. <i>panamensis</i> promastigotes were untreated (Control) or treated with 10 μM edelfosine at the indicated times, and cells with disrupted ΔΨ<sub>m</sub> (DiOC<sub>6</sub>(3)<sup>low</sup>) and ROS production (HE→Eth) were measured by flow cytometry. The numbers in each quadrant refer to the percentages of cells in each population. (<b>B</b>) <i>L</i>. <i>panamensis</i> promastigotes untreated (Control) and treated with edelfosine (EDLF) for 3 h were incubated with 2 μM HE and 10 μg/ml Hoechst 33342, and then analyzed by fluorescence microscopy. (<b>C</b>) <i>L</i>. <i>panamensis</i> promastigotes and (<b>D</b>) Jurkat cells were preincubated with 10 μg/ml CsA for 1 h, or with 10 mM NAC or 10 mM GSH for 2 h, and then incubated in the absence or presence of 10 μM edelfosine for 9 h. After treatment, the percentage of hypodiploid cells was analyzed by flow cytometry. Untreated control cells were run in parallel. (<b>E</b>) <i>L</i>. <i>panamensis</i> promastigotes and (<b>F</b>) Jurkat cells were preincubated with 10 μM rotenone, 5 mM malonate, 10 μM antimycin A, 1.5 mM azide, 50 μM CCCP or with 1 and 10 μM oligomycin (<i>L</i>. <i>panamensis</i> and Jurkat cells, respectively) for 1 h, and then incubated in the absence or presence of 10 μM edelfosine for 9 h. After treatment, cells producing ROS were quantified by flow cytometry. Untreated control cells were run in parallel. Data shown are means ± SD or representative of three independent experiments performed. Asterisks denote that the differences between the indicated groups (C and D) and with control cells (E and F) are statistically significant. (*) <i>P</i><0.05. (**) <i>P</i><0.01.</p>