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

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• 作者：Meryem Sari-Hassoun^a ; ^c ; Marie-Jeanne Clement^a ; Imane Hamdi^a ; Guillaume Bollot^b ; Cyril Bauvais^b ; Vandana Joshi^a ; Flavio Toma^a ; Andrea Burgo^a ; Michel Cailleret^a ; ¹ ; Martha Cecilia Rosales-herná ; ndez^d ; Martha Edith Macias Pé ; rez^d ; Daoudi Chabane-Sari^c ; Patrick A. Curmi^a ; ^{pcurmi@univ-evry.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cucurbitacin I (PubChem CID ; 5281321) ; Cucurbitacin E (PubChem CID ; 5281319) ; Cucurbitacin I 2-O-glucoside (PubChem CID ; 44201985) ; Cucurbitacin E 2-O-glucoside (PubChem CID ; 5459275) ; BMS3 (PubChem CID ; 644328) ; (± ; )-Blebbistatin (PubChem CID ; 3476986) ; Y27632 (PubChem CID ; 448042) ; NAC (PubChem CID ; 12035) ; GSH (PubChem CID ; 7048684) ; SMIFH2 (PubChem CID ; 2258538 ; SID ; 252158028)
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：102
• 期：Complete
• 页码：45-63
• 全文大小：5594 K

文摘

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.