Alpha-terthienyl increases filamentous actin of Entamoeba histolytica

Mol Biochem Parasitol. 2022 Nov:252:111512. doi: 10.1016/j.molbiopara.2022.111512. Epub 2022 Sep 6.

Abstract

This study aimed to know if alpha terthienyl (α-T) affects E. histolytica viability and to analyze its effect on the actin cytoskeleton. Trophozoites of E. histolytica HM1-IMSS were treated with α-T, then, cell viability and morphology were evaluated using tetrazolium salts and scanning electron microscopy, respectively; while actin filaments (F-actin) were stained with rhodamine-phalloidin, observed by confocal microscopy and quantified by fluorometry. Data showed that α-T inhibited cell viability of trophozoites (IC50, 19.43 µg / mL), affected the cell morphology, and increased the F-actin in a dose-dependent manner. Production of reactive oxygen species and RhoA-GTP levels remained normal in α-T-treated amebas. Two inhibitors that affect the organization of the trophozoites cytoskeleton, one that interacts directly with actin, Cytochalasin D (CD), and one that affects the Rho signaling pathway by inhibiting the downstream effector Rock, Y27632, were tested. Y27632 did not affect the increase of polymerized actin observed with α-T, this compound partially ameliorates the potent disrupting effects of CD on actin filaments. Docking results suggest that α-T could be an antagonist of CD for the same interaction zone in actin, however, more studies are needed to define the action mechanism of this compound.

Keywords: Actin; Adenophyllum aurantium; Asteraceae; Cytoskeleton; ROCK; Rho-GTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Actins* / drug effects
  • Actins* / metabolism
  • Animals
  • Entamoeba histolytica* / metabolism
  • Trophozoites / drug effects
  • Trophozoites / metabolism

Substances

  • Actins
  • alpha-terthienyl
  • Y 27632