Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/1459
Title: Cytotoxic effects and apoptotic signalling mechanisms of the sesquiterpenoid euplotin C, a secondary metabolite of the marine ciliate Euplotes crassus, in tumour cells
Authors: Cervia, Davide
Martini, Davide
Garcia-Gil, Mercedes
Di Giuseppe, Graziano
Guella, Graziano
Dini, Fernando
Bagnoli, Paola
Keywords: Ca2+ stores;Caspases;Cell death;Cytochrome c;Endoplasmic reticulum
Issue Date: 2006
Publisher: Springer Verlag
Source: Cervia, D. et al. 2006. Cytotoxic effects and apoptotic signalling mechanisms of the sesquiterpenoid euplotin C, a secondary metabolite of the marine ciliate Euplotes crassus, in tumour cells. "Apoptosis" 11:829-843
Abstract: 
Most antitumour agents with cytotoxic properties induce apoptosis. The lipophilic compound euplotin C, isolated from the ciliate Euplotes crassus, is toxic to a number of different opportunistic or pathogenic microorganisms, although its mechanism of action is currently unknown. We report here that euplotin C is a powerful cytotoxic and pro-apoptotic agent in mouse AtT-20 and rat PC12 tumour-derived cell lines. In addition, we provide evidence that euplotin C treatment results in rapid activation of ryanodine receptors, depletion of Ca2+ stores in the endoplasmic reticulum (ER), the release of cytochrome c from the mitochondria, activation of caspase-12, and activation of caspase-3, leading to apoptosis. Intracellular Ca2+ overload is an early event which induces apoptosis and is parallelled by ER stress and the release of cytochrome c, whereas caspase-12 may be activated by euplotin C at a later stage in the apoptosis pathway. These events, either independently or concomitantly, lead to the activation of the caspase-3 and its downstream effectors, triggering the cell to undergo apoptosis. These results demonstrate that euplotin C may be considered for the design of cytotoxic and pro-apoptotic new drugs.
Description: 
L'articolo è disponibile sul sito dell'editore http://www.springerlink.com/
URI: http://hdl.handle.net/2067/1459
ISSN: 1360-8185
DOI: 10.1007/s10495-006-5700-3
Appears in Collections:DISA - Archivio della produzione scientifica

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