scholarly journals FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3110 ◽  
Author(s):  
Dinh-Chuong Pham ◽  
Yu-Chuan Chang ◽  
Shian-Ren Lin ◽  
Yuh-Ming Fuh ◽  
May-Jywan Tsai ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Neuroblastoma Cells ◽  
Beclin 1 ◽  
Potential Candidate ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Anti Cancer

Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability. In an effort to determine the molecular mechanisms in neferine-incubated IMR32 cells, cell cycle arrest, cell migration, and focal adhesion kinase (FAK), the 70-kDa ribosomal S6 kinase 1 (S6K1), poly (ADP-ribose) polymerase (PARP), caspase-3, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein expressions were investigated. Neferine strongly disrupted the neuroblastoma cell growth via induction of G2/M phase arrest. Furthermore, neferine provoked autophagy and apoptosis in IMR32 cells, confirmed by p-FAK, and p-S6K1 reduction, LC3-II accumulation, Beclin-1 overexpression, and cleaved caspase-3/PARP improvement. Finally, neferine markedly retarded cell migration of neuroblastoma cancer cells. As a result, our findings for the first time showed an explicit anti-cancer effect of neferine in IMR32 cells, suggesting that neferine might be a potential candidate against human neuroblastoma cells to improve clinical outcomes with further in vivo investigation.

scholarly journals Zingerone Suppresses Tumor Development through Decreasing Cyclin D1 Expression and Inducing Mitotic Arrest

2018 ◽  
Vol 19 (9) ◽  
pp. 2832 ◽  
Author(s):  
Jae-Sun Choi ◽  
Jaewook Ryu ◽  
Woom-Yee Bae ◽  
Aron Park ◽  
Seungyoon Nam ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cells ◽  
Mitotic Arrest ◽  
Therapeutic Drug ◽  
Mouse Tumor ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Mitotic Cells

Cancer cells undergo uncontrolled proliferation resulting from aberrant activity of various cell-cycle proteins. Therefore, despite recent advances in intensive chemotherapy, it is difficult to cure cancer completely. Recently, cell-cycle regulators became attractive targets in cancer therapy. Zingerone, a phenolic compound isolated from ginger, is a nontoxic and inexpensive compound with varied pharmacological activities. In this study, the therapeutic effect of zingerone as an anti-mitotic agent in human neuroblastoma cells was investigated. Following treatment of BE(2)-M17 cells with zingerone, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and colony-formation assay to evaluate cellular proliferation, in addition to immunofluorescence cytochemistry and flow cytometry to examine the mitotic cells. The association of gene expression with tumor stage and survival was analyzed. Furthermore, to examine the anti-cancer effect of zingerone, we applied a BALB/c mouse-tumor model using a BALB/c-derived adenocarcinoma cell line. In human neuroblastoma cells, zingerone inhibited cellular viability and survival. Moreover, the number of mitotic cells, particularly those in prometaphase, increased in zingerone-treated neuroblastoma cells. Regarding specific molecular mechanisms, zingerone decreased cyclin D1 expression and induced the cleavage of caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1). The decrease in cyclin D1 and increase in histone H3 phosphorylated (p)-Ser10 were confirmed by immunohistochemistry in tumor tissues administered with zingerone. These results suggest that zingerone induces mitotic arrest followed by inhibition of growth of neuroblastoma cells. Collectively, zingerone may be a potential therapeutic drug for human cancers, including neuroblastoma.

scholarly journals Activation of caspase-3 alone is insufficient for apoptotic morphological changes in human neuroblastoma cells

2002 ◽  
Vol 80 (6) ◽  
pp. 1039-1048 ◽  
Author(s):  
Margaret M. Racke ◽  
Marian Mosior ◽  
Steve Kovacevic ◽  
Chan Hsin S. Chang ◽  
Andrew L. Glasebrook ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Morphological Changes ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Citicoline increases glutathione redox ratio and reduces caspase-3 activation and cell death in staurosporine-treated SH-SY5Y human neuroblastoma cells

2002 ◽  
Vol 957 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Marta Barrachina ◽  
Julio Secades ◽  
Rafael Lozano ◽  
Cristina Gómez-Santos ◽  
Santiago Ambrosio ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Redox Ratio ◽  
Glutathione Redox ◽  
Glutathione Redox Ratio

scholarly journals Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine strains in anin cellulomodel of human blood-brain barrier

2019 ◽  
Author(s):  
Cécile Khou ◽  
Marco Aurelio Díaz-Salinas ◽  
Anaelle da Costa ◽  
Christophe Préhaud ◽  
Patricia Jeannin ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Japanese Encephalitis ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cells ◽  
Brain Barrier ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Viral Determinants

ABSTRACTJapanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that JEV gets access to the central nervous system (CNS) as a consequence of a preceding inflammatory process which leads to the blood-brain barrier (BBB) disruption and viral neuroinvasion. However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross anin cellulohuman BBB model consisting of hCMEC/D3 human endothelial cells cultivated on permeable inserts above SK-N-SH human neuroblastoma cells. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post-addition. Furthermore, this BBB model was able to discriminate between the virulent RP9 and the vaccine SA14-14-2 strains, as demonstrated by the presence of almost 10 times more RP9 infectious particles that crossed the BBB than SA14-14 particles at a high MOI. Besides contributing to the understanding of early events in JEV neuroinvasion, thisin celluloBBB model represents a suitable and useful system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB at early times of neuroinvasion.

scholarly journals Stimulatory Heterotrimeric GTP-binding Protein Inhibits Hydrogen Peroxide-induced Apoptosis by Repressing BAK Induction in SH-SY5Y Human Neuroblastoma Cells

2007 ◽  
Vol 283 (3) ◽  
pp. 1350-1361 ◽  
Author(s):  
So-Young Kim ◽  
MiRan Seo ◽  
Yeni Kim ◽  
Yun-Il Lee ◽  
Jung-Min Oh ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cancer Cells ◽  
Neuroblastoma Cells ◽  
Camp Signaling ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Gtp Binding ◽  
Camp Signaling Pathway ◽  
Induced Apoptosis

Heterotrimeric stimulatory GTP-binding protein (Gs) stimulates adenylate cyclases to activate the cAMP signaling pathway. Although the cAMP pathway has been reported to be involved in apoptosis, the role of the Gs-cAMP signaling pathway during reactive oxygen species (ROS)-mediated apoptosis, which is involved in the resistance of cancer cells to chemotherapy and radiation, is not clearly understood. Thus, in this study we aimed to investigate the role of the α subunit of Gs (Gαs) in the ROS-induced apoptosis of cancer cells. The stable expression of constitutively active Gαs (GαsQL) inhibited the hydrogen peroxide-induced apoptosis of SH-SY5Y human neuroblastoma cells and reduced the hydrogen peroxide-induced increase in Bak and the decrease in Bcl-xL protein expression. Exogenous Bak expression abolished these inhibitory effects of GαsQL, but Bak small interfering RNA decreased hydrogen peroxide-induced apoptosis. Gαs repressed hydrogen peroxide-induced Bak expression by inhibiting the transcription of Bak mRNA, which resulted from the inhibition of the hydrogen peroxide-induced activation of transcription factors such as AP1, NF-κB, and NFAT. Moreover, Gαs also inhibited the hydrogen peroxide-induced binding of AP1, NF-κB, and NFAT to the Bak promoter. Furthermore, hydrogen peroxide-induced apoptosis was reduced by treating cells with prostaglandin E2, which activates Gαs, but this was augmented by CCPA, which activates Gαi causing a decrease in cAMP levels. From the results, we conclude that Gαs protects neuroblastoma cells from hydrogen peroxide-induced apoptosis by repressing Bak induction, which is mediated by the inhibition of the hydrogen peroxide-induced activations of AP1, NF-κB, and NFAT through cAMP-PKA-CREB signaling system.

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