Edelfosine induces breakage of kinetoplast DNA prior to nuclear DNA breakdown, and accumulates in mitochondria in Leishmania parasites and cancer cells.
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(A) L. panamensis promastigotes were untreated (Control) or treated with 10 μM edelfosine (EDLF) for 6 and 9 h, and then analyzed by confocal microscopy for propidium iodide (PI) staining and TUNEL assay. The positions of the nucleus (N) and kinetoplast (K) are indicated by arrows. Merging of PI and TUNEL panels (Merge) shows the DNA-containing organelles with DNA disruption in yellow. The corresponding differential interference contrast (DIC) images were included in the Merge panels to highlight parasite morphology and facilitate kinetoplast identification. (B) L. panamensis promastigotes and (C) HeLa cancer cells were incubated with 10 μM PTE-ET (blue fluorescence) for 1 h, 100 nM MitoTracker (red fluorescence) for 20 min to localize mitochondria, and then analyzed by fluorescence microscopy. Areas of colocalization between mitochondria and PTE-ET in merge panels are purple. The corresponding differential interference contrast (DIC) images are also shown. Images are representative of three independent experiments. Bar, 20 μm.