Arsenic Trioxide Inhibits Neuroblastoma Growth in Vivo and Promotes Apoptotic Cell Death in Vitro

2000 ◽  
Vol 277 (1) ◽  
pp. 179-185 ◽  
Author(s):  
Ingrid Øra ◽  
Lennart Bondesson ◽  
Carolin Jönsson ◽  
June Ljungberg ◽  
Isabella Pörn-Ares ◽  
...  
Keyword(s):  
Cell Death ◽  
Arsenic Trioxide ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death

scholarly journals Sindbis Virus-Induced Neuronal Death Is both Necrotic and Apoptotic and Is Ameliorated byN-Methyl-d-Aspartate Receptor Antagonists

2001 ◽  
Vol 75 (15) ◽  
pp. 7114-7121 ◽  
Author(s):  
Jennifer L. Nargi-Aizenman ◽  
Diane E. Griffin
Keyword(s):  
Cell Death ◽  
Cortical Neurons ◽  
Sindbis Virus ◽  
Apoptotic Cell ◽  
Time Lapse ◽  
Apoptotic Cell Death ◽  
Time Lapse Imaging ◽  
Alphavirus Infection

ABSTRACT Virus infection of neurons leads to different outcomes ranging from latent and noncytolytic infection to cell death. Viruses kill neurons directly by inducing either apoptosis or necrosis or indirectly as a result of the host immune response. Sindbis virus (SV) is an alphavirus that induces apoptotic cell death both in vitro and in vivo. However, apoptotic changes are not always evident in neurons induced to die by alphavirus infection. Time lapse imaging revealed that SV-infected primary cortical neurons exhibited both apoptotic and necrotic morphological features and that uninfected neurons in the cultures also died. Antagonists of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors protected neurons from SV-induced death without affecting virus replication or SV-induced apoptotic cell death. These results provide evidence that SV infection activates neurotoxic pathways that result in aberrant NMDA receptor stimulation and damage to infected and uninfected neurons.

Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo

2018 ◽  
Vol 233 (9) ◽  
pp. 7134-7142 ◽  
Author(s):  
Long-Bin Jeng ◽  
Bharath Kumar Velmurugan ◽  
Ming-Cheng Chen ◽  
Hsi-Hsien Hsu ◽  
Tsung-Jung Ho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Colorectal Cancer Cells

Protective Effect of Anthocyanins from Black Soybean Seed Coats on UVB-Induced Apoptotic Cell Death in Vitro and in Vivo

2008 ◽  
Vol 56 (22) ◽  
pp. 10600-10605 ◽  
Author(s):  
Konstantin Tsoyi ◽  
Hyung Bin Park ◽  
Young Min Kim ◽  
Jong Il Chung ◽  
Sung Chul Shin ◽  
...  
Keyword(s):  
Cell Death ◽  
Protective Effect ◽  
Apoptotic Cell ◽  
Soybean Seed ◽  
Apoptotic Cell Death ◽  
Black Soybean ◽  
Seed Coats

scholarly journals CXCR4 Blockade By BL-8040 in T Cell Acute Lymphoblastic Leukemia Decreases Mitochondrial Mass and Induces Non-Apoptotic Cell Death

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2745-2745
Author(s):  
Jun Xia ◽  
Stephanie Sun ◽  
Matthew RM Jotte ◽  
Geoffrey L. Uy ◽  
Osnat Bohana-Kashtan ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Lymphoblastic Leukemia ◽  
Apoptotic Cell Death ◽  
Employment Equity ◽  
Cxcr4 Signaling ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Equity Ownership

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that accounts for 10-15% of pediatric and 25% of adult ALL cases. CXCL12 is a CXC chemokine that is constitutively expressed at high levels in the bone marrow. CXCR4 is the major receptor for CXCL12 and is by far the most highly expressed chemokine receptor on T-ALL cells. Two groups recently showed that genetic loss of CXCR4 signaling in murine or human T-ALL cells markedly suppressed their growth in vivo. We previously reported that BL-8040, a potent new CXCR4 antagonist with sustained receptor occupancy, is active as monotherapy against T-ALL in mice. Indeed, a 2-week course of daily BL-8040 resulted in a median reduction in tumor burden of 32.1-fold (range 6.8 to 176) across 5 different T-ALL xenografts. Preliminary data from a clinical trial of BL-8040 plus nelarabine for relapsed T-ALL also suggest therapeutic activity, with a complete remission rate observed in 4/8 patients (50%), which compares favorably to published response rates of approximately 30% with single agent nelarabine. Here, we explore molecular mechanisms by which CXCR4 blockade induces T-ALL death. NOD-scid IL2Rgammanull (NSG) mice were injected with P12-Ichikawa cells, a T-ALL cell line modified to express click beetle red luciferase and GFP. Following T-ALL engraftment, mice were treated with a single dose of BL-8040, and then leukemic cells in the bone marrow harvested 24-48 hours later. Treatment with BL-8040 resulted in a marked suppression of Akt and Erk1/2 phosphorylation, suggesting that signaling through CXCR4 is the major source of PI3 kinase pathway activation in T-ALL cells. Surprisingly, treatment with BL-8040 did not affect cellular proliferation, as measured by Ki67/FxCycle Violet staining or by EdU labeling. Moreover, no increase in apoptosis, as measured by annexin V or activated caspase 3 expression, was observed. These data suggest that CXCR4 blockade induces a non-apoptotic cell death. To explore this possibility further, we performed transcriptome sequencing on T-ALL cells recovered from mice 24 hours after 1 dose of BL-8040. A total of 151 differentially expressed genes (FDR of < 0.05% and ≥ 2-fold change) were identified. Gene set enrichment analysis was strongly positive for alterations in oxidative phosphorylation, ribosome biogenesis, and carbohydrate metabolism. Ribosome function was assessed using O-propargyl-puromycin (OPP), which monitors global protein translation. No difference in global protein synthesis in T-ALL cells was observed after CXCR4 blockade in vivo. T-ALL cells are dependent on glutamine as a source of carbon, and PI3 kinase signaling positively regulates glutaminolysis. Thus, we hypothesized that CXCR4 blockade may induce T-ALL cell death by reducing glutamine metabolism. However, treatment of T-ALL cells in vitro with BL-8040 did not alter the cellular levels of glutamine or glutamate, as measured using a commercial bioluminescent assay. Confirmatory metabolic tracing studies using 13C-labeled glutamine and glucose are in progress. Finally, to explore the reduction in oxidative phosphorylation, we examined mitochondria function using Mitotracker Green. Treatment of T-ALL cells in vitro with BL-8040 for 24-48 hours induced a significant decrease in mitochondria number, suggesting induction of mitophagy. Collectively, these data suggest that T-ALL cells are addicted to CXCR4 signaling in vivo. CXCR4 blockade with BL-8040 induces a non-apoptotic cell death that is characterized by a loss of mitochondria. Disclosures Uy: Astellas: Consultancy; Pfizer: Consultancy; Curis: Consultancy; GlycoMimetics: Consultancy. Bohana-Kashtan:BiolineRx: Employment, Equity Ownership. Sorani:BiolineRx: Employment, Equity Ownership. Vainstein:BiolineRx: Employment, Equity Ownership.

scholarly journals Cell Death and Ageing – A Question of Cell Type

2002 ◽  
Vol 2 ◽  
pp. 943-948 ◽  
Author(s):  
Pidder Jansen-Dürr
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Replicative Senescence ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Ageing Process ◽  
Human Ageing

Replicative senescence of human cells in primary culture is a widely accepted model for studying the molecular mechanisms of human ageing. The standard model used for studying human ageing consists of fibroblasts explanted from the skin and grown intoin vitrosenescence. From this model, we have learned much about molecular mechanisms underlying the human ageing process; however, the model presents clear limitations. In particular, a long-standing dogma holds that replicative senescence involves resistance to apoptosis, a belief that has led to considerable confusion concerning the role of apoptosis during human ageing. While there are data suggesting that apoptotic cell death plays a key role for ageingin vitroand in the pathogenesis of various age-associated diseases, this is not reflected in the current literature onin vitrosenescence. In this article, I summarize key findings concerning the relationship between apoptosis and ageingin vivoand also review the literature concerning the role of apoptosis during in vitro senescence. Recent experimental findings, summarized in this article, suggest that apoptotic cell death (and probably other forms of cell death) are important features of the ageing process that can also be recapitulated in tissue culture systems to some extent. Another important lesson to learn from these studies is that mechanisms ofin vivosenescence differ considerably between various histotypes.

scholarly journals bcl-x Prevents Apoptotic Cell Death of Both Primitive and Definitive Erythrocytes at the End of Maturation

1999 ◽  
Vol 189 (11) ◽  
pp. 1691-1698 ◽  
Author(s):  
Noboru Motoyama ◽  
Tohru Kimura ◽  
Tomomi Takahashi ◽  
Takeshi Watanabe ◽  
Toru Nakano
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Es Cells ◽  
Embryonic Stem ◽  
Apoptotic Cell Death ◽  
Null Mouse ◽  
Stromal Cell Line ◽  
Macrophage Colony

bcl-x is a member of the bcl-2 gene family, which regulates apoptotic cell death in various cell lineages. There is circumstantial evidence suggesting that bcl-x might play a role in the apoptosis of erythroid lineage cells, although there is no direct evidence. In this study, we used Bcl-X null mouse embryonic stem (ES) cells, and showed that Bcl-X is indispensable for the production of both embryonic primitive erythrocytes (EryP) and adult definitive erythrocytes (EryD) at the end of their maturation. In vivo, bcl-x−/− ES cells did not contribute to circulating EryD in adult chimeric mice that were produced by blastocyst microinjection of the bcl-x−/− ES cells. bcl-x−/− EryP and EryD were produced by in vitro differentiation induction of ES cells on macrophage colony-stimulating factor–deficient stromal cell line OP9, and further analysis was carried out. The emergence of immature EryP and EryD from bcl-x−/− ES cells was similar to that from bcl-x+/+ ES cells. However, prominent cell death of bcl-x−/− EryP and EryD occurred when the cells matured. The data show that the antiapoptotic function of bcl-x acts at the very end of erythroid maturation.

scholarly journals Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and autophagy in in vitro and in vivo models

2007 ◽  
Vol 98 (2) ◽  
pp. 399-409 ◽  
Author(s):  
A Ogata ◽  
H Yanagie ◽  
E Ishikawa ◽  
Y Morishita ◽  
S Mitsui ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Antitumour Effect ◽  
In Vivo Models

scholarly journals The brominated flame retardant BDE-47 causes oxidative stress and apoptotic cell death in vitro and in vivo in mice

2015 ◽  
Vol 48 ◽  
pp. 68-76 ◽  
Author(s):  
Lucio G. Costa ◽  
Claudia Pellacani ◽  
Khoi Dao ◽  
Terrance J. Kavanagh ◽  
Pamela J. Roque
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Flame Retardant ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Brominated Flame Retardant

scholarly journals Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 890
Author(s):  
Dahae Lee ◽  
Jaemin Lee ◽  
Kim Long Vu-Huynh ◽  
Thi Hong Van Le ◽  
Thi Hong Tuoi Do ◽  
...  
Keyword(s):  
Cell Death ◽  
Protective Effect ◽  
Renal Damage ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Body Weight Loss ◽  
Apoptotic Cell Death ◽  
In Vivo Studies

Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 μM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 μM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 μM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.

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