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 (1, 2) , Marie-Jeanne Clément (1) , Imane Hamdi (1) , Guillaume Bollot (3) , Cyril Bauvais (3) , Vandana Joshi (1) , Flavio Toma (1) , Andrea Burgo (1) , Michel Cailleret (1) , Martha Cecilia Rosales-Hernández (4) , Martha Edith Macias Pérez (4) , Daoudi Chabane-Sari (2) , Patrick A. Curmi (1)

1 SABNP - Structure et activité des biomolécules normales et pathologiques
2 Université Aboubekr Belkaid - University of Belkaïd Abou Bekr [Tlemcen]
3 Synsight
4 Instituto politecnico national (Mexico)

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.

Keywords: (±)-Blebbistatin (PubChem CID: 3476986); Actin; BMS3 (PubChem CID: 644328); Cucurbitacin; Cucurbitacin E (PubChem CID: 5281319); Cucurbitacin E 2-O-glucoside (PubChem CID: 5459275); Cucurbitacin I (PubChem CID: 5281321); Cucurbitacin I 2-O-glucoside (PubChem CID: 44201985); GSH (PubChem CID: 7048684); LIMK; Myosin II; NAC (PubChem CID: 12035); ROCK; SMIFH2 (PubChem CID: 2258538; SID: 252158028); Y27632 (PubChem CID: 448042)

Domains: Life Sciences [q-bio]

Meryem Sari-Hassoun, Marie-Jeanne Clément, Imane Hamdi, Guillaume Bollot, Cyril Bauvais, et al.. Cucurbitacin I elicits the formation of actin/phospho-myosin II co-aggregates by stimulation of the RhoA/ROCK pathway and inhibition of LIM-kinase. Biochemical Pharmacology, 2016, 102, pp.45-63. ⟨10.1016/j.bcp.2015.12.013⟩. ⟨hal-02183418⟩