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Ultrastructural Expansion Microscopy in Three In Vitro Life Cycle Stages of Trypanosoma cruzi
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Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process

Malena Landoni1, Tamara Piñero1, Luciana L Soprano2

  • 1Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET, CIHIDECAR, Intendente Güiraldes 2160, C1428GA, Ciudad Universitaria, Buenos Aires, Argentina.

Biochemical and Biophysical Research Communications
|July 7, 2019
PubMed

Insights

Tamoxifen, an anti-cancer drug, disrupts the sphingolipid pathway in Trypanosoma cruzi, leading to parasite death. This study identifies potential new therapeutic targets for treating Chagas disease.

Area of Science:

  • Parasitology
  • Biochemistry
  • Drug Discovery

Background:

  • Trypanosoma cruzi causes Chagas disease, a neglected tropical illness.
  • The sphingolipid pathway is crucial for parasite survival and a potential drug target.

Purpose of the Study:

  • To investigate the effects of tamoxifen on the T. cruzi sphingolipid pathway.
  • To explore tamoxifen as a potential chemotherapeutic agent against T. cruzi.

Main Methods:

  • Dose-dependent growth inhibition assays for epimastigotes, trypomastigotes, and intracellular amastigotes.
  • Metabolic labeling, thin-layer chromatography, MALDI-TOF, and HPLC-ESI mass spectrometry to analyze sphingolipid levels.
  • Ultrastructural analysis and flow cytometry to assess cell death mechanisms.

Main Results:

  • Tamoxifen inhibited T. cruzi growth in a dose-dependent manner.
  • Significant lysis of blood trypomastigotes and inhibition of intracellular amastigotes were observed.
  • Tamoxifen treatment dramatically increased ceramide levels and altered ceramide-1P and sphingosine levels, indicating interference with ceramide breakdown.
  • Parasites exhibited morphological and molecular characteristics of apoptotic-like cell death.

Conclusions:

  • Tamoxifen effectively targets the T. cruzi sphingolipid pathway, inducing an apoptotic-like death process.
  • The drug's action on ceramide metabolism suggests a novel mechanism for antiparasitic activity.
  • Tamoxifen demonstrates potential as a chemotherapeutic agent for Chagas disease, warranting further investigation.
Keywords:
Apoptotic-like processLipidomicsSphingolipidsTrypanosoma cruzitamoxifen

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