Bergamottin and 5-Geranyloxy-7-methoxycoumarin Cooperate in the Cytotoxic Effect of Citrus bergamia (Bergamot) Essential Oil in Human Neuroblastoma SH-SY5Y Cell Line

The plant kingdom has always been a treasure trove for valuable bioactive compounds, and Citrus fruits stand out among the others. Bergamottin (BRG) and 5-geranyloxy-7-methoxycoumarin (5-G-7-MOC) are two coumarins found in different Citrus species with well-acknowledged pharmacological properties. Previously, they have been claimed to be relevant in the anti-proliferative effects exerted by bergamot essential oil (BEO) in the SH-SY5Y human neuroblastoma cells. This study was designed to verify this assumption and to assess the mechanisms underlying the anti-proliferative effect of both compounds. Our results demonstrate that BRG and 5-G-7-MOC are able to reduce the proliferation of SH-SY5Y cells, inducing apoptosis and increasing cell population in sub-G0/G1 phase. Moreover, we demonstrated the pro-oxidant activity of the two coumarins that increased reactive oxygen species and impaired mitochondrial membrane potential. From a molecular point of view, BRG and 5-G-7-MOC were able to modulate apoptosis related factors at both protein and gene levels. Lastly, we evaluated the synergistic effect of their combination, finding that the highest synergy was observed at a concentration ratio similar to that occurring in the BEO, supporting our initial hypothesis. Taken together, our results deepen the knowledge regarding the effect of BRG and 5-G-7-MOC in SH-SY5Y cells, emphasizing the relevance of their cooperation in achieving this effect.

Download Full-text

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1670759 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 2

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.

Download Full-text

The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin

Bioscience Reports ◽

10.1042/bsr20171611 ◽

2018 ◽

Vol 38 (1) ◽

Cited By ~ 6

Author(s):

Chol Seung Lim ◽

Jung-Soo Han

Keyword(s):

Therapeutic Potential ◽

Neuroblastoma Cells ◽

Amyloid Β ◽

Enzymatic Activities ◽

Oxidative Modification ◽

Amyloid Β Peptide ◽

Oxygen Species ◽

Human Neuroblastoma Cells ◽

Neuroprotective Effects ◽

Human Neuroblastoma

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory properties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced oxidative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities of NEP protein were measured. Increased HNE levels on NEP proteins and reduced enzymatic activities of NEP were observed in the HNE- or oligomeric Aβ42-treated cells. Xan reduced HNE levels on NEP proteins and preserved enzymatic activities of NEP in HNE- or oligomeric Aβ42-treated cells. Xan reduced Aβ42 accumulation and protected neurones against oligomeric Aβ42-induced neurotoxicity through preservation of NEP activities. These findings indicate that Xan possesses therapeutic potential for the treatment of neurodegenerative diseases, including AD, and suggest a potential mechanism for the neuroprotective effects of antioxidants for the prevention of AD.

Download Full-text

Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells

Antioxidants ◽

10.3390/antiox9010050 ◽

2020 ◽

Vol 9 (1) ◽

pp. 50 ◽

Cited By ~ 8

Author(s):

Silvana Alfei ◽

Barbara Marengo ◽

Cinzia Domenicotti

Keyword(s):

Drug Loading ◽

Neuroblastoma Cells ◽

Entrapment Efficiency ◽

Synergistic Action ◽

Multi Drug Resistance ◽

Oxygen Species ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Per Se ◽

Oxidant Effect

Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX 5) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (−45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX 5 was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX 5 is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells.

Download Full-text

Reactive Oxygen Species Regulate the Levels of Dual Oxidase (Duox1-2) in Human Neuroblastoma Cells

PLoS ONE ◽

10.1371/journal.pone.0034405 ◽

2012 ◽

Vol 7 (4) ◽

pp. e34405 ◽

Cited By ~ 23

Author(s):

Simona Damiano ◽

Roberta Fusco ◽

Annalisa Morano ◽

Mariarosaria De Mizio ◽

Roberto Paternò ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Neuroblastoma Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Dual Oxidase

Download Full-text

Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells

Cancer Letters ◽

10.1016/j.canlet.2011.09.005 ◽

2011 ◽

Vol 313 (2) ◽

pp. 201-210 ◽

Cited By ~ 20

Author(s):

Qi Zhang ◽

Yan Ma ◽

Yue-Fang Cheng ◽

Wen-Jie Li ◽

Zhenzhong Zhang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Neuroblastoma Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Induced Apoptosis

Download Full-text

Rac1-NADPH oxidase-regulated generation of reactive oxygen species mediates glutamate-induced apoptosis in SH-SY5Y human neuroblastoma cells

Free Radical Research ◽

10.1080/10715760500176866 ◽

2005 ◽

Vol 39 (12) ◽

pp. 1295-1304 ◽

Cited By ~ 34

Author(s):

Sevdalina Nikolova ◽

Yong Soo Lee ◽

Yoon-Seok Lee ◽

Jung-ae Kim

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Neuroblastoma Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Human Neuroblastoma Cells ◽

Human Neuroblastoma ◽

Induced Apoptosis

Download Full-text

Moringin from Moringa Oleifera Seeds Inhibits Growth, Arrests Cell-Cycle, and Induces Apoptosis of SH-SY5Y Human Neuroblastoma Cells through the Modulation of NF-κB and Apoptotic Related Factors

International Journal of Molecular Sciences ◽

10.3390/ijms20081930 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1930 ◽

Cited By ~ 13

Author(s):

Santa Cirmi ◽

Nadia Ferlazzo ◽

Agnese Gugliandolo ◽

Laura Musumeci ◽

Emanuela Mazzon ◽

...

Keyword(s):

Cell Cycle ◽

Mechanism Of Action ◽

Nuclear Translocation ◽

Neuroblastoma Cells ◽

Transcriptional Level ◽

Human Neuroblastoma Cells ◽

Related Factors ◽

Human Neuroblastoma ◽

Drug Mechanism ◽

Apoptotic Cascade

In the last decades, glucosinolates (GLs), precursors of isothiocyanates (ITCs), have been studied mostly for their chemopreventive and chemotherapeutic properties. The aim of our research was to study the antiproliferative effect of 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (glucomoringin; GMG) bioactivated by myrosinase enzyme to form the corresponding isothiocyanate 4-(α-L-rhamnopyranosyloxy) benzyl C (moringin) in SH-SY5Y human neuroblastoma cells. We found that moringin significantly reduced SH-SY5Y cell growth in a time and concentration-dependent (p < 0.05, 0.01, and 0.001 vs. ctrl, after treatment with 16.4 µM moringin for 24, 48, and 72 h, respectively) manner through a mechanism involving the activation of apoptotic machinery. In addition, it altered the normal progression of cells through the cell cycle, increasing the cell population in both G2 and S phases, as well as decreasing that in the G1 phase. Studying the drug mechanism of action, we found that moringin was able to increase the expression of p53, p21, and Bax at both the protein and transcriptional level. Moreover, exposure of SH-SY5Y cells to moringin significantly increased the gene expression of both caspase 3 and 9 and enhanced their cleavage, thereby initiating an intrinsic apoptotic cascade. Finally, moringin inhibited nuclear translocation of NF-κB. Our study demonstrates the ability of moringin to reduce the growth of SH-SY5Y cells and reveals its mechanism of action, suggesting its promising role as an anticancer drug.

Download Full-text