title: Plasmodium falciparum: erythrocytic stages die by autophagic-like cell death under drug pressure.
abstract: It has been reported that an apoptotic cell death process can occur with protozoans, but no consensus on Plasmodium susceptibility to apoptosis was reached till now. Thus, we evaluated if Plasmodium falciparum blood forms undergo apoptosis after in vitro pressure with chloroquine, S-nitroso-N-acetyl-penicillamine (SNAP) or staurosporine. Inhibition of parasite growth and loss of viability were observed in treated cultures by both light microscopy and flow cytometry. When DNA fragmentation was verified, only a small number of TUNEL-positive parasites was detected in treated cultures and pretreatment of parasite with a general caspase inhibitor was not able to prevent parasite death. Considering the lack of apoptotic characteristics and the observation of parasites with cytoplasmatic vacuolization by electron microscopy, we conclude that P. falciparum parasites under chloroquine, SNAP or staurosporine pressures do not die by apoptosis but by a process similar to autophagy. The autophagic pathway could be explored as an alternative target for the development of new antimalarial drugs.
authors.affiliation: Laboratory of Malaria Research, Instituto Oswaldo Cruz, Fiocruz, Pavilhão Leônidas Deane, Manguinhos, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Paulo Renato Rivas
authors.initials: PR
authors.lastname: Totino
authors.forename: Cláudio Tadeu
authors.initials: CT
authors.lastname: Daniel-Ribeiro
authors.forename: Suzana
authors.initials: S
authors.lastname: Corte-Real
authors.forename: Maria
authors.initials: M
authors.lastname: de Fátima Ferreira-da-Cruz
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D053938:DNA Fragmentation; D004912:Erythrocytes / Q000469:parasitology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D020112:Rhodamine 123; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D061945:Caspase Inhibitors; D005456:Fluorescent Dyes; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D020112:Rhodamine 123; D002738:Chloroquine; D010396:Penicillamine; D019311:Staurosporine