Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells

Axelsson, Viktoria; Holback, Sofia; Sjögren, Maria H.; Gustafsson, Helena; Forsby, Anna

doi:10.1016/j.bbrc.2006.05.019

Cited by 20 publications

(14 citation statements)

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“…Gliotoxin could effectively induce programmed cell death, suggesting that it could be a promising anticancer. The previous study investigated the cytotoxicity induced by gliotoxin in human hepatic stellate, rat Kupffer and SH-SY5Y cells [18,21,22]. In this study, we reported for the first time an evaluation of the effects of gliotoxin on the growth of Hela and SW1353 cells in vitro .…”

Section: Resultsmentioning

confidence: 95%

“…Several papers have also reported the importance of gliotoxin as induction of membrane permeability transition and caspase-3 activation [18,22,30]. Caspases are expressed in almost all cell types as inactive proenzymes.…”

Section: Resultsmentioning

confidence: 99%

“…One of them, gliotoxin, belongs to the family of epipolythiodioxopiperazines that is characterized by a disulfide bridge across a piperazine ring (Figure 1). Gliotoxin, one of the secondary metabolites produced by a number of Aspergillus , Gliocladium and Penicillium species, is a tricyclic alkaloid [18,19,20]. Gliotoxin is an inducer of apoptotic cell death in a number of cell types [21,22,23].…”

Section: Introductionmentioning

confidence: 99%

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Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells

et al. 2013

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Gliotoxin, a secondary metabolite produced by marine fungus Aspergillus sp., possesses various biological activities including anticancer activity. However, the mechanism underlying gliotoxin-induced cytotoxicity on human cervical cancer (Hela) and human chondrosarcoma (SW1353) cells remains unclear. In this study, we focused on the effect of gliotoxin induction on apoptosis, the activating expressions of caspase family enzymes in the cells. Apoptotic cell levels were measured through DAPI and Annexin V/Propidium Iodide (PI) double staining analysis. The apoptotic protein expression of Bcl-2 and caspase family was detected by Western blot in Hela and SW1353 cells. Our results showed that gliotoxin treatment inhibited cell proliferation and induced significant morphological changes. Gliotoxin induced apoptosis was further confirmed by DNA fragmentation, chromatin condensation and disrupted mitochondrial membrane potential. Gliotoxin-induced activation of caspase-3, caspase-8 and caspase-9, down-regulation of Bcl-2, up-regulation of Bax and cytochromec (cyt c) release showed evidence for the gliotoxin activity on apoptosis. These findings suggest that gliotoxin isolated from marine fungus Aspergillus sp. induced apoptosis in Hela and SW1353 cells via the mitochondrial pathway followed by downstream events leading to apoptotic mode of cell death.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells

et al. 2013

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“…Western blotting was carried out essentially as described by (Gorina et al 2005). Transferred proteins on polyvinylidene difluoride membranes were incubated overnight at 4°C with one of the following primary antibodies: monoclonal antibody against cytochrome c (clone 7H8.2C12, BD Biosciences/Pharmingen, Madrid, Spain) at a 1 : 1000 dilution; polyclonal antibody against AIF (Serotec/Bionova, Madrid, Spain) at a 1 : 2000 dilution; monoclonal antibody against heat‐shock protein 70 (Hsp70, clone W27, Millipore, Madrid, Spain) at a 1 : 2000 dilution; a polyclonal antibody against VDAC (ab15895, Abcam Ltd, Cambridge, UK) used at a 1 : 1000 dilution; a polyclonal antibody against α‐actin (Sigma, Madrid, Spain), used at 1 : 5000; a monoclonal antibody against TATA‐binding protein (ab818, Abcam Ltd, Cambridge UK), used at 1 : 2000; a monoclonal antibody against Lamin A/C (clone JOL2, Millipore, Madrid, Spain), used at 1 : 200, and a monoclonal antibody against αII‐spectrin that recognizes an epitope in the C‐terminal region of the protein (MAB1622, Millipore, Madrid, Spain) (Axelsson et al 2006), used at 1 : 1000. The blots were further incubated for 1 h with the following dilutions of the horseradish peroxidase‐conjugated anti‐IgG Immunoglobulins of the appropriate specificity: 1 : 1000 (Lamin A/C), 1 : 2000 (cytochrome c, AIF, Hsp70, TATA‐binding protein) or 1 : 10000 (VDAC, α‐actin).…”

Section: Methodsmentioning

confidence: 99%

Glucose promotes caspase‐dependent delayed cell death after a transient episode of oxygen and glucose deprivation in SH‐SY5Y cells

Serra-Pérez

Verdaguer

Planas

et al. 2008

Journal of Neurochemistry

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Brain ischemia causes neuronal cell death by several mechanisms involving necrotic and apoptotic processes. The contributions of each process depend on conditions such as the severity and duration of ischemia, and the availability of ATP. We examined whether glucose affected the development of apoptosis after transient ischemia, and whether this was sensitive to caspase inhibition. Retinoic acid-differentiated SH-SY5Y human neuroblastoma cells were subjected to oxygen and glucose deprivation for 15 h followed by various periods of reoxygenation in either the presence or absence of glucose. Oxygen and glucose deprivation induced cell death in the hours following reoxygenation, as detected by propidium iodide staining. At the end of the period of oxygen and glucose deprivation, both cytochrome c and apoptosis-inducing factor translocated from mitochondria to cytosol. Reoxygenation in the presence of glucose accelerated cell death, and enhanced caspase-3 activity and apoptosis. The glucosedependent increase in apoptosis was prevented by treatment with the caspase inhibitor zVAD-fmk, but not with calpeptin, a calpain inhibitor. Nevertheless, both zVAD-fmk and calpeptin decreased cell death in the glucose-treated group. ATP levels dropped dramatically after oxygen and glucose deprivation, but recovered steadily thereafter, and were significantly higher at 6 h of reoxygenation in the glucose-treated group. This indicates that energy recovery may promote the glucosedependent cell death. We conclude that glucose favours the development of caspase-dependent apoptosis during reoxygenation following oxygen and glucose deprivation. Cao et al. 2003;Plesnila et al. 2004;Culmsee et al. 2005). Apoptosis has also been identified in peri-infarction areas of the human brain after stroke (Sairanen et al. 2006). Apoptosis is an energy-dependent process that needs the development and execution of a cell death programme (Alison and Sarraf 1992). For this reason, the availability of energy substrates might condition the type of cell death (Nicotera et al. 1998). Indeed, high glucose induces a switch from necrosis to apoptosis (Fujita and Ueda 2003;Ueda and Fujita 2004), whereas ATP depletion has the opposite effect (Eguchi et al. 1997). Here we sought to evaluate whether glucose availability and ATP level after a transient period of ischemia affected the development of apoptotic cell death, and whether this type of death could be blocked by caspase inhibition. We developed a model of delayed cell death in differentiated SH-SY5Y neuroblastoma cells transiently exposed to a period of oxygen and glucose deprivation (OGD) and then reoxygenated either in the presence or in the absence of glucose. Our results show that glucose accelerates cell death after ischemia by promoting caspase-dependent apoptosis. Materials and Methods MaterialsMost chemicals used were from SIGMA. All-trans-retinoic acid (RA) was purchased from Calbiochem/Bionova (Madrid, Spain). zVAD-fmk and calpeptin were from Bachem (Weil am Rhein, Germany), and were diss...

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“…Aspergillus species are filamentous saprophytic fungi that can be found in almost all aerobic environments, which possessed antitumor, anti-inflammatory, antiviral and antibacterial activity [90]. Gliotoxin, one of the secondary metabolites produced by a number of Aspergillus , Gliocladium and Penicillium species, is a tricyclic alkaloid [91,92,93]. Gliotoxin effectively reduced the proliferation of HPV18 transformed Hela cells and could induce apoptotic cell death in association with the loss of mitochondrial membrane potential (MMP), and activation of Bax, caspase-3, caspase-8 and caspase-9, as well as suppression of Bcl-2 [94].…”

Section: Potential Anti-hpv and Related Cancer Agents From Marine mentioning

confidence: 99%

Potential Anti-HPV and Related Cancer Agents from Marine Resources: An Overview

et al. 2014

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Recently, the studies on the prevention and treatment of human papillomavirus (HPV) which is closely related to the cervical cancer and other genital diseases are attracting more and more attention all over the world. Marine-derived polysaccharides and other bioactive compounds have been shown to possess a variety of anti-HPV and related cancer activities. This paper will review the recent progress in research on the potential anti-HPV and related cancer agents from marine resources. In particular, it will provide an update on the anti-HPV actions of heparinoid polysaccharides and bioactive compounds present in marine organisms, as well as the therapeutic vaccines relating to marine organisms. In addition, the possible mechanisms of anti-HPV actions of marine bioactive compounds and their potential for therapeutic application will also be summarized in detail.

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Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells

Cited by 20 publications

References 47 publications

Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells

Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells

Glucose promotes caspase‐dependent delayed cell death after a transient episode of oxygen and glucose deprivation in SH‐SY5Y cells

Potential Anti-HPV and Related Cancer Agents from Marine Resources: An Overview

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