scholarly journals 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

2019 ◽  
Vol 20 (8) ◽  
pp. 1930 ◽  
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.

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 Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells

Oncogene ◽  
2005 ◽  
Vol 24 (36) ◽  
pp. 5606-5618 ◽  
Author(s):  
Christopher J Wallick ◽  
Ivonne Gamper ◽  
Mike Thorne ◽  
David J Feith ◽  
Kelsie Y Takasaki ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Neuroblastoma Cells ◽  
Retinoblastoma Protein ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

scholarly journals Repression of BIRC5/Survivin by FOXO3/FKHRL1 Sensitizes Human Neuroblastoma Cells to DNA Damage-induced Apoptosis

2009 ◽  
Vol 20 (7) ◽  
pp. 2041-2048 ◽  
Author(s):  
Petra Obexer ◽  
Judith Hagenbuchner ◽  
Thomas Unterkircher ◽  
Nora Sachsenmaier ◽  
Christoph Seifarth ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Chemotherapy Resistance ◽  
Neuroblastoma Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Human Neuroblastoma Cells ◽  
Hairpin Rna ◽  
Human Neuroblastoma ◽  
Dna Damaging Agents ◽  
Induced Apoptosis

The phosphatidylinositol 3-kinase (PI3K)–protein kinase B (PKB) pathway regulates survival and chemotherapy resistance of neuronal cells, and its deregulation in neuroblastoma (NB) tumors predicts an adverse clinical outcome. Here, we show that inhibition of PI3K-PKB signaling in human NB cells induces nuclear translocation of FOXO3/FKHRL1, represses the prosurvival protein BIRC5/Survivin, and sensitizes to DNA-damaging agents. To specifically address whether FKHRL1 contributes to Survivin regulation, we introduced a 4-hydroxy-tamoxifen-regulated FKHRL1(A3)ERtm allele into NB cells. Conditional FKHRL1 activation repressed Survivin transcription and protein expression. Transgenic Survivin exerted a significant antiapoptotic effect and prevented the accumulation of Bim and Bax at mitochondria, the loss of mitochondrial membrane potential as well as the release of cytochrome c during FKHRL1-induced apoptosis. In concordance, Survivin knockdown by retroviral short hairpin RNA technology accelerated FKHRL1-induced apoptosis. Low-dose activation of FKHRL1 sensitized to the DNA-damaging agents doxorubicin and etoposide, whereas the overexpression of Survivin diminished FKHRL1 sensitization to these drugs. These results suggest that repression of Survivin by FKHRL1 facilitates FKHRL1-induced apoptosis and sensitizes to cell death induced by DNA-damaging agents, which supports the central role of PI3K-PKB-FKHRL1 signaling in drug resistance of human NB.

scholarly journals Involvement of Dihydroceramide Desaturase in Cell Cycle Progression in Human Neuroblastoma Cells

2007 ◽  
Vol 282 (23) ◽  
pp. 16718-16728 ◽  
Author(s):  
Jacqueline M. Kraveka ◽  
Li Li ◽  
Zdzislaw M. Szulc ◽  
Jacek Bielawski ◽  
Besim Ogretmen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Cycle Progression ◽  
Dihydroceramide Desaturase

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

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 275
Author(s):  
Alessandro Maugeri ◽  
Giovanni Enrico Lombardo ◽  
Laura Musumeci ◽  
Caterina Russo ◽  
Sebastiano Gangemi ◽  
...  
Keyword(s):  
Essential Oil ◽  
Neuroblastoma Cells ◽  
Point Of View ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Related Factors ◽  
Human Neuroblastoma ◽  
Proliferative Effect ◽  
Initial Hypothesis ◽  
Citrus Bergamia

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.

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