Cucurbitacin i elicits the formation of actin/phospho-myosin II co-aggregates by stimulation of the RhoA/ROCK pathway and inhibition of LIM-kinase

Meryem Sari-Hassoun, Marie Jeanne Clement, Imane Hamdi, Guillaume Bollot, Cyril Bauvais, Vandana Joshi, Flavio Toma, Andrea Burgo, Michel Cailleret, Martha Cecilia Rosales-Hernández, Martha Edith Macias Pérez, Daoudi Chabane-Sari, Patrick A. Curmi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Cucurbitacins are cytotoxic triterpenoid sterols isolated from plants. One of their earliest cellular effect is the aggregation of actin associated with blockage of cell migration and division that eventually lead to apoptosis. We unravel here that cucurbitacin I actually induces the co-aggregation of actin with phospho-myosin II. This co-aggregation most probably results from the stimulation of the Rho/ROCK pathway and the direct inhibition of the LIMKinase. We further provide data that suggest that the formation of these co-aggregates is independent of a putative pro-oxidant status of cucurbitacin I. The results help to understand the impact of cucurbitacins on signal transduction and actin dynamics and open novel perspectives to use it as drug candidates for cancer research.

Original languageEnglish
Pages (from-to)45-63
Number of pages19
JournalBiochemical Pharmacology
Volume102
DOIs
StatePublished - 15 Feb 2016

Keywords

  • Actin
  • Cucurbitacin
  • LIMK
  • Myosin II
  • ROCK

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