Cytotoxic effects and apoptotic signalling mechanisms of the sesquiterpenoid euplotin C, a secondary metabolite of the marine ciliate Euplotes crassus, in tumour cells

Apoptosis : an International Journal on Programmed Cell Death
Davide CerviaPaola Bagnoli

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.

References

Feb 1, 1996·Journal of Neurochemistry·G TrainaP Bagnoli
Oct 23, 1997·International Review of Cytology·S T ChristensenD N Wheatley
Nov 21, 1998·Nature·M Raff
Mar 19, 1999·Journal of Neuroscience Research·C P Fall, J P Bennett
Aug 23, 2000·The Journal of Cell Biology·K NakamuraM Michalak
Nov 17, 2001·Current Opinion in Pharmacology·A B da RochaG Schwartsmann
Nov 21, 2001·Nature Cell Biology·K F Ferri, G Kroemer
Jan 17, 2002·Neurochemistry International·Laura ColombaioniMercedes Garcia-Gil
Feb 16, 2002·Journal of Hematotherapy & Stem Cell Research·Angelo VaccaFranco Dammacco
Mar 29, 2002·The Journal of Biological Chemistry·Rammohan V RaoH Michael Ellerby
Apr 12, 2002·Brain Research. Developmental Brain Research·Laura ColombaioniMercedes Garcia-Gil
Jun 5, 2002·Human Molecular Genetics·Yoriko KourokuTakashi Momoi
Sep 28, 2002·Blood·Irene M PedersenJohn C Reed
Mar 19, 2003·Journal of Neurochemistry·Krishna Pada SarkerIkuro Maruyama
Mar 26, 2003·Cell Death and Differentiation·S NagataH Fukuyama
May 15, 2003·British Journal of Pharmacology·Davide CerviaDaniel Hoyer
May 23, 2003·Molecular Pharmacology·Franz-Josef BraunJames W Putney
Jun 25, 2003·Drug Discovery Today·Burkhard Haefner
Jul 3, 2003·Nature Reviews. Molecular Cell Biology·Sten OrreniusPierluigi Nicotera
Jul 25, 2003·European Journal of Pharmacology·Xiao-Chun ChenChao-Hui Zhao
Oct 17, 2003·The Journal of Biological Chemistry·Rammohan V RaoDale E Bredesen
Dec 17, 2003·Journal of Neurochemistry·Stephen F LarnerKevin K W Wang
Dec 20, 2003·Cell Death and Differentiation·M LamkanfiP Vandenabeele
Feb 7, 2004·Cell Death and Differentiation·R V RaoD E Bredesen
Mar 23, 2004·Annals of the New York Academy of Sciences·Eva SzegezdiAfshin Samali

❮ Previous
Next ❯

Citations

Sep 25, 2009·Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology·Paola RamoinoCesare Usai
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Djalila MekahliLudwig Missiaen
Apr 19, 2007·Apoptosis : an International Journal on Programmed Cell Death·Davide CerviaFernando Dini
Feb 12, 2014·The Journal of Eukaryotic Microbiology·Federico BuonannoClaudio Ortenzi
Jan 27, 2009·Journal of Neuroscience Research·L Di Cesare MannelliC Ghelardini
Nov 20, 2008·The Journal of Eukaryotic Microbiology·Francesca TrielliFernando Dini
Aug 19, 2008·Journal of Neuroscience Research·Lorenzo Di Cesare MannelliAlessandro Bartolini
Aug 24, 2007·The European Journal of Neuroscience·Lorenzo Di Cesare MannelliA Bartolini
Jun 17, 2009·The Journal of Eukaryotic Microbiology·Davide CerviaFernando Dini
Jul 23, 2013·Journal of Biochemical and Molecular Toxicology·Mauro C X PintoElaine M de Souza-Fagundes
Aug 30, 2008·Chemico-biological Interactions·Federico BuonannoClaudio Ortenzi
Nov 13, 2013·The American Journal of Pathology·Cristiana PerrottaDavide Cervia
Oct 21, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Elisabetta CatalaniDavide Cervia
Aug 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jiaen WeiZunnan Huang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis