scholarly journals Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives

2020 ◽  
Vol 14 (1) ◽  
pp. 10
Author(s):  
Lara Rouco ◽  
Ángeles Sánchez-González ◽  
Rebeca Alvariño ◽  
Amparo Alfonso ◽  
Ezequiel M. Vázquez-López ◽  
...  
Keyword(s):  
Cell Death ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Neuroblastoma Cells ◽  
Fluorescence Analysis ◽  
Benzimidazole Derivatives ◽  
Human Neuroblastoma ◽  
Gold Compounds ◽  
Pre Treatment ◽  
Standard Techniques

Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh3)) (1) or triethylphosphine (Au(pben)(PEt3)) (2) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC50) was determined. 1 and 2 showed an IC50 of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms.

scholarly journals 4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cytotoxic Effect ◽  
Neuroblastoma Cells ◽  
Reactive Oxygen ◽  
Prognostic Indicator ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

scholarly journals Inhibition of autophagy by 3-methyladenine potentiates sulforaphane-induced cell death of BE(2)-C human neuroblastoma cells

2012 ◽  
Vol 12 (1) ◽  
pp. 535-542 ◽  
Author(s):  
IRENA HORWACIK ◽  
MONIKA GAIK ◽  
MAŁGORZATA DURBAS ◽  
ELŻBIETA BORATYN ◽  
GRZEGORZ ZAJĄC ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells

1994 ◽  
Vol 14 (10) ◽  
pp. 6584-6596
Author(s):  
G Melino ◽  
M Annicchiarico-Petruzzelli ◽  
L Piredda ◽  
E Candi ◽  
V Gentile ◽  
...  
Keyword(s):  
Cell Death ◽  
Structural Changes ◽  
Tissue Transglutaminase ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Transfected Cells ◽  
Protein Levels

In this report, we show that the overexpression of tissue transglutaminase (tTG) in the human neuroblastoma cell line SK-N-BE(2) renders these neural crest-derived cells highly susceptible to death by apoptosis. Cells transfected with a full-length tTG cDNA, under the control of a constitutive promoter, show a drastic reduction in proliferative capacity paralleled by a large increase in cell death rate. The dying tTG-transfected cells exhibit both cytoplasmic and nuclear changes characteristic of cells undergoing apoptosis. The tTG-transfected cells express high Bcl-2 protein levels as well as phenotypic neural cell adhesion molecule markers (NCAM and neurofilaments) of cells differentiating along the neuronal pathway. In keeping with these findings, transfection of neuroblastoma cells with an expression vector containing segments of the human tTG cDNA in antisense orientation resulted in a pronounced decrease of both spontaneous and retinoic acid (RA)-induced apoptosis. We also present evidence that (i) the apoptotic program of these neuroectodermal cells is strictly regulated by RA and (ii) cell death by apoptosis in the human neuroblastoma SK-N-BE(2) cells preferentially occurs in the substrate-adherent phenotype. For the first time, we report here a direct effect of tTG in the phenotypic maturation toward apoptosis. These results indicate that the tTG-dependent irreversible cross-linking of intracellular protein represents an important biochemical event in the induction of the structural changes featuring cells dying by apoptosis.

scholarly journals Mitochondrial Peptide Humanin Protects Silver Nanoparticles-Induced Neurotoxicity in Human Neuroblastoma Cancer Cells (SH-SY5Y)

2019 ◽  
Vol 20 (18) ◽  
pp. 4439 ◽  
Author(s):  
Gurunathan ◽  
Jeyaraj ◽  
Kang ◽  
Kim
Keyword(s):  
Oxidative Stress ◽  
Silver Nanoparticles ◽  
Protective Effect ◽  
Anticancer Agents ◽  
Membrane Integrity ◽  
Neuroblastoma Cells ◽  
Human Beings ◽  
Human Neuroblastoma ◽  
Cellular Effects ◽  
Harmful Effects

The extensive usage of silver nanoparticles (AgNPs) as medical products such as antimicrobial and anticancer agents has raised concerns about their harmful effects on human beings. AgNPs can potentially induce oxidative stress and apoptosis in cells. However, humanin (HN) is a small secreted peptide that has cytoprotective and neuroprotective cellular effects. The aim of this study was to assess the harmful effects of AgNPs on human neuroblastoma SH-SY5Y cells and also to investigate the protective effect of HN from AgNPs-induced cell death, mitochondrial dysfunctions, DNA damage, and apoptosis. AgNPs were prepared with an average size of 18 nm diameter to study their interaction with SH-SY5Y cells. AgNPs caused a dose-dependent decrease of cell viability and proliferation, induced loss of plasma-membrane integrity, oxidative stress, loss of mitochondrial membrane potential (MMP), and loss of ATP content, amongst other effects. Pretreatment or co-treatment of HN with AgNPs protected cells from several of these AgNPs induced adverse effects. Thus, this study demonstrated for the first time that HN protected neuroblastoma cells against AgNPs-induced neurotoxicity. The mechanisms of the HN-mediated protective effect on neuroblastoma cells may provide further insights for the development of novel therapeutic agents against neurodegenerative diseases.

scholarly journals Neuroprotective Effect of Bergamot Juice in 6-OHDA-Induced SH-SY5Y Cell Death, an In Vitro Model of Parkinson’s Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 326 ◽  
Author(s):  
Nadia Ferlazzo ◽  
Santa Cirmi ◽  
Alessandro Maugeri ◽  
Caterina Russo ◽  
Giovanni Enrico Lombardo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nuclear Translocation ◽  
Neuroprotective Effect ◽  
Neuroblastoma Cells ◽  
Specific Cell ◽  
Protective Effects ◽  
Human Neuroblastoma

Much evidence suggests that both oxidative stress and apoptosis play a key role in the pathogenesis of Parkinson’s disease (PD). The present study aims to evaluate the protective effect of bergamot juice (BJ) against 6-hydroxydopamine (6-OHDA)- or H2O2-induced cell death. Treatment of differentiated SH-SY5Y human neuroblastoma cells with 6-OHDA or H2O2 resulted in cell death that was significantly reduced by the pre-treatment with BJ. The protective effects of BJ seem to correlate with the reduction of intracellular reactive oxygen species and nitric oxide generation caused by 6-OHDA or H2O2. BJ also attenuated mitochondrial dysfunction, caspase-3 activation, imbalance of pro- and anti-apoptotic proteins, MAPKs activation and reduced NF-ĸB nuclear translocation evoked by neurotoxic agents. Additionally, BJ exhibited excellent antioxidant capability in cell-free assays. Collectively, our results suggest that BJ exerts neuroprotective effect through the interplay with specific cell targets and its antioxidant activity, making it worthy of consideration for the management of neurodegenerative diseases.

scholarly journals The Effects of Oleuropein on Different Clinically Types of Human Neuroblastoma Cells

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1591
Author(s):  
Zekiye Altun ◽  
Efe Ozgur Serinan ◽  
Merve Tütüncü ◽  
Safiye Aktaş ◽  
Nur Olgun
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Model Organisms ◽  
Late Relapse ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonic tumor originating from the neural crest. It accounts for 8–10% of all childhood cancers. Although Cisplatin is used in neuroblastoma treatment, it has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. One herbal agent that has attracted attention in recent years is oleuropein (OLE), the active component of olive leaf. This component belongs to the polyphenol group and it has antioxidant, anti-microbial, anti-inflammatory, anti-hypertensive and anti-carcinogenic effects. It has beneficial effects against neurodegeneration in both culture cells and model organisms. Oleuropein has been shown to be increased apoptosis in SH-SY5Y neuroblastoma cell line in one study. Cisplatin (cis-diaminedichloroplatinum II (CDDP) is a widely used agent for the treatment of many different human cancers in childhood and adults with antimitotic and antineoplastic properties. CDDP is the most effective chemotherapeutic agent in specially treatment of neuroblastoma. Purpose of this study was to determine whether oleuropein and CDDP have possible anti-proliferative activity in different types of human neuroblastoma cells as representing different clinical features (bone marrow metastatic LAN-5 cells and treated with chemotherapy and beam therapy CHP-134 cells representing late relapse) investigated. Human bone marrow metastatic LAN-5 and treated with chemotherapy and beam therapy CHP-134 neuroblastoma cells representing late relapse were used in this study. The effects of OLE and CDDP on LAN-5 and CHP-134 neuroblastoma cell proliferation and apoptotic cell death was investigated using WST-1 cell proliferation and Annexin-V/PI flow cytometric assays. Oleuropein and CDDP have been shown to inhibit proliferation of LAN-5 and CHP-134 neuroblastoma cells. In further studies, it is planned to investigate different cell death mechanisms by using combination of oleuropein and cisplatin in different kind of human neuroblastoma cells.

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