Kaempferol inhibits Entamoeba histolytica growth by altering cytoskeletal functions

Mol Biochem Parasitol. 2015 Nov;204(1):16-25. doi: 10.1016/j.molbiopara.2015.11.004. Epub 2015 Nov 24.

Abstract

The flavonoid kaempferol obtained from Helianthemum glomeratum, an endemic Mexican medicinal herb used to treat gastrointestinal disorders, has been shown to inhibit growth of Entamoeba histolytica trophozoites in vitro; however, the mechanisms associated with this activity have not been documented. Several works reported that kaempferol affects cytoskeleton in mammalian cells. In order to gain insights into the action mechanisms involved in the anti-amoebic effect of kaempferol, here we evaluated the effect of this compound on the pathogenic events driven by the cytoskeleton during E. histolytica infection. We also carried out a two dimensional gel-based proteomic analysis to evidence modulated proteins that could explain the phenotypical changes observed in trophozoites. Our results showed that kaempferol produces a dose-dependent effect on trophozoites growth and viability with optimal concentration being 27.7 μM. Kaempferol also decreased adhesion, it increased migration and phagocytic activity, but it did not affect erythrocyte binding nor cytolytic capacity of E. histolytica. Congruently, proteomic analysis revealed that the cytoskeleton proteins actin, myosin II heavy chain and cortexillin II were up-regulated in response to kaempferol treatment. In conclusion, kaempferol anti-amoebic effects were associated with deregulation of proteins related with cytoskeleton, which altered invasion mechanisms.

Keywords: Cytoskeleton; Entamoeba histolytica; Flavonoids; Kaempferol; Pathogenicity; Proteomic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cistaceae / chemistry
  • Cytoskeletal Proteins / metabolism
  • Cytoskeleton / drug effects*
  • Cytoskeleton / physiology
  • Dose-Response Relationship, Drug
  • Entamoeba histolytica / drug effects*
  • Entamoeba histolytica / growth & development
  • Entamoeba histolytica / metabolism
  • Entamoebiasis / drug therapy
  • Entamoebiasis / parasitology
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology
  • Humans
  • Kaempferols / pharmacology*
  • Mexico
  • Phagocytosis / drug effects
  • Plants, Medicinal / chemistry
  • Proteomics
  • Protozoan Proteins / metabolism*
  • Trophozoites / drug effects*
  • Trophozoites / growth & development
  • Trophozoites / metabolism

Substances

  • Cytoskeletal Proteins
  • Kaempferols
  • Protozoan Proteins
  • kaempferol