Statins and voriconazole induce programmed cell death in Acanthamoeba castellanii.
Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a life-threatening encephalitis. In order to treat those infections properly, it is necessary to target the treatment not only to the trophozoite but also to the cyst. Furthermore, it may be advantageous to avoid parasite killing by necrosis, which may induce local inflammation. We must also avoid toxicity of host tissue. Many drugs which target eukaryotes are known to induce programmed cell death (PCD), but this process is poorly characterized in Acanthamoeba. Here, we study the processes of programmed cell death in Acanthamoeba, induced by several drugs, such as statins and voriconazole. We tested atorvastatin, fluvastatin, simvastatin, and voriconazole at the 50% inhibitory concentrations (IC50s) and IC90s that we have previously established. In order to evaluate this phenomenon, we investigated the DNA fragmentation, one of the main characteristics of PCD, with quantitative and qualitative techniques. Also, the changes related to phosphatidylserine exposure on the external cell membrane and cell permeability were studied. Finally, because caspases are key to PCD pathways, caspase activity was evaluated in Acanthamoeba. All the drugs assayed in this study induced PCD in Acanthamoeba. To the best of our knowledge, this is the first study where PCD induced by drugs is described quantitatively and qualitatively in Acanthamoeba.
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain cmmartin@ull.es.
Carmen M
CM
Martín-Navarro
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
Atteneri
A
López-Arencibia
Laboratoire Matériaux-Molécules et Applications, IPEST, La Marsa, University of Carthage, Tunis, Tunisia.
Ines
I
Sifaoui
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
María
M
Reyes-Batlle
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
Basilio
B
Valladares
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
Enrique
E
Martínez-Carretero
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
José E
JE
Piñero
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Sutherland K
SK
Maciver
University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
Jacob
J
Lorenzo-Morales
D048248:Acanthamoeba castellanii / Q000187:drug effects*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D019821:Simvastatin / Q000494:pharmacology; D065819:Voriconazole / Q000494:pharmacology*
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D019821:Simvastatin; D065819:Voriconazole