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Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells
- Source :
- Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Autophagy is a crucial and physiological process for cell survival from yeast to mammals, including protozoan parasites. Toxoplasma gondii, an intracellular parasite, typically exploits autophagic machinery of host cell; however host cell upregulates autophagy to combat the infection. Herein we tested the efficacy of Rottlerin, a natural polyphenol with autophagic promoting properties, against Toxoplasma infection on the chorioncarcinoma-derived cell line BeWo. We found that Rottlerin, at sub-toxic doses, induced morphological and biochemical alterations associated with autophagy and decreased Toxoplasma growth in infected cells. Although autophagy was synergically promoted by Toxoplasma infection in combination with Rottlerin treatment, the use of the autophagy inhibitor chloroquine revealed that Rottlerin anti-parasitic effect was largely autophagy-independent and likely mediated by the converging inhibitory effect of Rottlerin and Toxoplasma in host protein translation, mediated by mTOR inhibition and eIF2α phosphorylation. Both events, which on one hand could explain the additive effect on autophagy induction, on the other hand led to inhibition of protein synthesis, thereby depriving Toxoplasma of metabolically essential components for multiplication. We suggest that modulation of the competition between pathogen requirement and host cell defense might be an attractive, novel therapeutic approach against Toxoplasma infection and encourage the development of Rottlerin-based new therapeutic formulations.
- Subjects :
- 0301 basic medicine
Science
Antiprotozoal Agents
Article
Cell Line
03 medical and health sciences
chemistry.chemical_compound
parasitic diseases
Autophagy
Humans
Benzopyrans
Pathogen
PI3K/AKT/mTOR pathway
Multidisciplinary
biology
Intracellular parasite
Acetophenones
Toxoplasma gondii
Translation (biology)
biology.organism_classification
Trophoblasts
Cell biology
030104 developmental biology
chemistry
Cell culture
Protein Biosynthesis
Medicine
Toxoplasma
Rottlerin
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....3d95e635b83b201441781e14e4b3ddf8