title: Cucurbitacin I elicits the formation of actin/phospho-myosin II co-aggregates by stimulation of the RhoA/ROCK pathway and inhibition of LIM-kinase.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France; Laboratoire des Produits Naturels, LAPRONA, Université Abou Bekr Belkaid, Tlemcen 13000, Algeria.
authors.forename: Meryem
authors.initials: M
authors.lastname: Sari-Hassoun
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France.
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Clement
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France.
authors.forename: Imane
authors.initials: I
authors.lastname: Hamdi
authors.affiliation: Synsight, 86 Rue de Paris, 91400 Orsay, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bollot
authors.affiliation: Synsight, 86 Rue de Paris, 91400 Orsay, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Bauvais
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France.
authors.forename: Vandana
authors.initials: V
authors.lastname: Joshi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France.
authors.forename: Flavio
authors.initials: F
authors.lastname: Toma
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Burgo
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cailleret
authors.affiliation: Laboratorio de Biofísica y Biocatalisis, Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, México D.F. 11340, México.
authors.forename: Martha Cecilia
authors.initials: MC
authors.lastname: Rosales-Hernández
authors.affiliation: Laboratorio de Biofísica y Biocatalisis, Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, México D.F. 11340, México.
authors.forename: Martha Edith
authors.initials: ME
authors.lastname: Macias Pérez
authors.affiliation: Laboratoire des Produits Naturels, LAPRONA, Université Abou Bekr Belkaid, Tlemcen 13000, Algeria.
authors.forename: Daoudi
authors.initials: D
authors.lastname: Chabane-Sari
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR1204, Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, Université d'Evry-Val d'Essonne, Evry 91025, France. Electronic address: pcurmi@univ-evry.fr.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Curmi
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005578:Fosfomycin / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D054461:Lim Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D024462:Myosin Type II / Q000737:chemistry / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012639:Seeds; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014315:Triterpenes; D005578:Fosfomycin; C515892:LIMK1 protein, human; D054461:Lim Kinases; D054460:rho-Associated Kinases; D024462:Myosin Type II; C038106:cucurbitacin I
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)