Dihydroartemisinin induces ER stress-dependent apoptosis of Echinococcus protoscoleces in vitro

Acta Biochim Biophys Sin (Shanghai). 2020 Oct 19;52(10):1140-1147. doi: 10.1093/abbs/gmaa101.

Abstract

In this study, we investigated the effect of dihydroartemisinin on Echinococcus protoscoleces and explored the role of endoplasmic reticulum stress in this process. Echinococcus protoscoleces were collected and cultured in RPMI 1640 medium. Changes in the expressions of glucose-regulated protein 78 (GRP-78), caspase-12, and C/EBP homologous protein (CHOP) were assessed through confocal immunofluorescence and western blot analysis. Cell viability and morphological changes were observed under a light microscope. The ultrastructure of protoscoleces was observed by scanning electron microscopy and transmission electron microscopy. Caspase-3 activity was detected using an enzyme assay kit. After dihydroartemisinin treatment, the protoscoleces showed loss of viability, and morphological changes including soma contraction, blebs formation, hooks loss, microtrichia destruction, and development of lipid droplets was observed. The levels of caspase-12 and CHOP were increased within 2 days of dihydroartemisinin treatment. However, the levels of GRP-78, caspase-12, and CHOP were decreased in 4 days. Furthermore, caspase-3 activity was increased after treatment with different concentrations of dihydroartemisinin. Dihydroartemisinin can induce apoptosis in protoscoleces via the ER stress-caspase-3 apoptotic pathway in vitro. These results indicate that dihydroartemisinin is a potentially valuable therapeutic agent against echinococcosis.

Keywords: ER stress; apoptosis; dihydroartemisinin; oxidative stress.

MeSH terms

  • Animals
  • Anthelmintics / pharmacology*
  • Apoptosis / drug effects*
  • Artemisinins / pharmacology*
  • Caspase 12 / metabolism
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Duration of Therapy
  • Echinococcus / cytology
  • Echinococcus / drug effects*
  • Echinococcus / growth & development
  • Echinococcus / ultrastructure
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects*
  • Heat-Shock Proteins / metabolism
  • Microscopy
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Transcription Factor CHOP / metabolism

Substances

  • Anthelmintics
  • Artemisinins
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins
  • Transcription Factor CHOP
  • artenimol
  • Caspase 12
  • Caspase 3