The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei.

ABSTRACT:

Background

Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization.

Methods

We measured drug concentrations that inhibit cell proliferation by 50% (IC_{50) for several compounds, chosen based on their lysosomotropic effects previously reported in Plasmodium falciparum. The lysosomal effects and cell death induced by L-leucyl-L-leucyl methyl ester (LeuLeu-OMe) were further analyzed by flow cytometry and immunofluoresc}

SUBMITTER: Koh HX 

PROVIDER: S-EPMC5349101 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature