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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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Cervia et al-Apoptosis 2006 1.pdf | 157.46 kB | Adobe PDF | View/Open |
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