Antitumoral Effects of Curcumin (Curcuma longa L.) and Thymoquinone (Nigella sativa L.) on Neuroblastoma Cell Lines

2020 ◽  
pp. 1-5
Author(s):  
Johanna Maria Korff ◽  
Katrin Menke ◽  
Melanie Schwermer ◽  
Katharina Falke ◽  
Alexander Schramm ◽  
...  
Keyword(s):  
Cell Lines ◽  
Nigella Sativa ◽  
Curcuma Longa ◽  
Neuroblastoma Cell ◽  
Primary Human Fibroblast ◽  
Cytotoxic Effects ◽  
Anti Cancer ◽  
Ic50 Values ◽  
Neuroblastoma Cell Lines

<b><i>Introduction:</i></b> Overall survival of high-risk neuroblastoma patients is still poor, emphasizing the need for novel therapeutic options. There is evidence for anti-cancer properties of the herbal substances thymoquinone and curcumin. These substances are isolated from <i>Nigella sativa</i> L. and <i>Curcuma longa</i> L., respectively, which are used in traditional medicine. <b><i>Objective:</i></b> We investigated cytotoxic effects of thymoquinone and curcumin on neuroblastoma cell lines NLF, NB69, and SK-N-BE(2), in vitro. <b><i>Methods:</i></b> Cytotoxicity of compounds was investigated by MTT cell viability assays. For analyzing effects on cell proliferation BrdU assays were employed and induction of apoptosis was detected by Cell Death ELISA assays. <b><i>Results:</i></b> Both substances showed cytotoxic effects in all three neuroblastoma cell lines, whereby primary human fibroblast cells reacted less sensitively. Overall, lower IC50 values could be calculated for curcumin (3.75–7.42 µM) than for thymoquinone (5.16–16.3 µM). Decreased proliferation and increased apoptosis rates were observed under treatment. <b><i>Conclusions:</i></b> Both substances showed anti-tumoral properties on neuroblastoma cell lines and should be further investigated as therapeutic agents.

scholarly journals Anti-cancer effects of bortezomib against chemoresistant neuroblastoma cell lines in vitro and in vivo

2006 ◽  
Author(s):  
Martin Michaelis ◽  
Iduna Fichtner ◽  
Diana Behrens ◽  
Wolfram Haider ◽  
Florian Rothweiler ◽  
...  
Keyword(s):  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Anti Cancer ◽  
Neuroblastoma Cell Lines

scholarly journals Anti-Cancer Effect of Kaffir Lime (Citrus Hystrix DC) Leaf Extract in Cervical Cancer and Neuroblastoma Cell Lines

2015 ◽  
Vol 14 ◽  
pp. 465-468 ◽  
Author(s):  
Woro Anindito Sri Tunjung ◽  
Jindrich Cinatl ◽  
Martin Michaelis ◽  
C. Mark Smales
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Leaf Extract ◽  
Neuroblastoma Cell ◽  
Anti Cancer ◽  
Neuroblastoma Cell Lines

scholarly journals A Context-Dependent Role for MiR-124-3p on Cell Phenotype, Viability and Chemosensitivity in Neuroblastoma in vitro

2020 ◽  
Vol 8 ◽  
Author(s):  
John C. Nolan ◽  
Manuela Salvucci ◽  
Steven Carberry ◽  
Ana Barat ◽  
Miguel F. Segura ◽  
...  
Keyword(s):  
Cell Lines ◽  
Epithelial To Mesenchymal Transition ◽  
Neuroblastoma Cell ◽  
Chemotherapy Resistance ◽  
Cellular Transformation ◽  
Cell Phenotype ◽  
Drug Resistant ◽  
Mesenchymal Transition ◽  
Neuroblastoma Cell Lines

Neuroblastoma (NB) is a neural crest-derived tumor, which develops before birth or in early childhood, with metastatic dissemination typically preceding diagnosis. Tumors are characterized by a highly heterogeneous combination of cellular phenotypes demonstrating varying degrees of differentiation along different lineage pathways, and possessing distinct super-enhancers and core regulatory circuits, thereby leading to highly varied malignant potential and divergent clinical outcomes. Cytoskeletal reorganization is fundamental to cellular transformations, including the processes of cellular differentiation and epithelial to mesenchymal transition (EMT), previously reported by our lab and others to coincide with chemotherapy resistance and enhanced metastatic ability of tumor cells. This study set out to investigate the ability of the neuronal miR-124-3p to reverse the cellular transformation associated with drug resistance development and assess the anti-oncogenic role of this miRNA in in vitro models of drug-resistant adrenergic (ADRN) and mesenchymal (MES) neuroblastoma cell lines. Low expression of miR-124-3p in a cohort of neuroblastomas was significantly associated with poor overall and progression-free patient survival. Over-expression of miR-124-3p in vitro inhibited cell viability through the promotion of cell cycle arrest and induction of apoptosis in addition to sensitizing drug-resistant cells to chemotherapeutics in a panel of morphologically distinct neuroblastoma cell lines. Finally, we describe miR-124-3p direct targeting and repression of key up-regulated cytoskeletal genes including MYH9, ACTN4 and PLEC and the reversal of the resistance-associated EMT and enhanced invasive capacity previously reported in our in vitro model (SK-N-ASCis24).

In vitro cytotoxicity of fenthion and related metabolites in human neuroblastoma cell lines

Chemosphere ◽  
1995 ◽  
Vol 30 (9) ◽  
pp. 1709-1715 ◽  
Author(s):  
D. Cova ◽  
R. Perego ◽  
C. Nebuloni ◽  
G. Fontana ◽  
G.P. Molinari
Keyword(s):  
Cell Lines ◽  
Neuroblastoma Cell ◽  
In Vitro Cytotoxicity ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Neuroblastoma Cell Lines

Taurolidine Specifically Inhibits Growth of Neuroblastoma Cell Lines In Vitro

2014 ◽  
Vol 36 (4) ◽  
pp. e219-e223 ◽  
Author(s):  
Christian Luckert ◽  
Georg Eschenburg ◽  
Beate Roth ◽  
Birgit Appl ◽  
Konrad Reinshagen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Lines

scholarly journals The choroid plexus may be an underestimated site of tumor invasion to the brain: an in vitro study using neuroblastoma cell lines

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Elodie Vandenhaute ◽  
Carolin Stump-Guthier ◽  
María Lasierra Losada ◽  
Tobias Tenenbaum ◽  
Henriette Rudolph ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Cell Lines ◽  
Tumor Invasion ◽  
Neuroblastoma Cell ◽  
In Vitro Study ◽  
Vitro Study ◽  
Neuroblastoma Cell Lines ◽  
The Brain

scholarly journals ALT Neuroblastoma Chemoresistance due to ATM Activation by Telomere Dysfunction is Reversible with the ATM Inhibitor AZD0156

2021 ◽  
Author(s):  
Balakrishna Koneru ◽  
Ahsan Farooqi ◽  
Thinhh H. Nguyen ◽  
Wan Hsi Chen ◽  
Ashly Hindle ◽  
...  
Keyword(s):  
Cell Lines ◽  
De Novo ◽  
Clinical Stage ◽  
Neuroblastoma Cell ◽  
Telomere Dysfunction ◽  
Atm Kinase ◽  
Kinase Activation ◽  
Neuroblastoma Cell Lines

AbstractCancers overcome replicative immortality by activating either telomerase or an alternative lengthening of telomeres (ALT) mechanism. ALT occurs in ∼ 25% of high-risk neuroblastomas and relapse or progression in ALT neuroblastoma patients during or after front-line therapy is frequent and almost uniformly fatal. Temozolomide + irinotecan is commonly used as salvage therapy for neuroblastoma. Patient-derived cell-lines and xenografts established from relapsed ALT neuroblastoma patients demonstrated de novo resistance to temozolomide + irinotecan (as SN-38 in vitro, P<0.05) and in vivo (mouse event-free survival (EFS) P<0.0001) relative to telomerase-positive neuroblastomas. We observed that ALT neuroblastoma cells manifest constitutive ATM kinase activation due to spontaneous telomere dysfunction while telomerase- positive tumors lacked constitutive ATM activation or spontaneous telomere DNA damage. We demonstrated that induction of telomere dysfunction resulted in ATM activation that in turn conferred resistance to temozolomide + SN-38 (4.2 fold-change in IC50, P<0.001). ATM kinase shRNA knock-down or inhibition using a clinical-stage small molecule inhibitor (AZD0156) reversed resistance to temozolomide + irinotecan in ALT neuroblastoma cell-lines in vitro (P<0.001) and in 4 ALT xenografts in vivo (EFS P<0.0001). AZD0156 showed modest to no enhancement of temozolomide + irinotecan activity in telomerase-positive neuroblastoma cell lines and xenografts. ATR inhibition using AZD6738 did not enhance temozolomide + SN-38 activity in ALT neuroblastoma cell lines. Thus, resistance to chemotherapy in ALT neuroblastoma occurs via ATM kinase activation and was reversed with the ATM inhibitor AZD0156. Combining AZD0156 with temozolomide + irinotecan warrants clinical testing in neuroblastoma.One Statement SummaryATM activation at telomeres confers resistance to DNA damaging chemotherapy in ALT neuroblastoma that was reversed with ATM knockdown or inhibition.

scholarly journals Itchy E3 ubiquitin-protein ligase promotes neuroblastoma progression in vitro and in vivo

2021 ◽  
Vol 3 (4) ◽  
pp. 12-24
Author(s):  
Mabao YUAN ◽  
Hanjiao HANG ◽  
Lubin YAN ◽  
Xuanjie HUANG ◽  
Ziyang SANG ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Luciferase Reporter ◽  
Ubiquitin Protein Ligase ◽  
Neuroblastoma Cell Lines ◽  
Dual Luciferase Reporter Assay

[Objective] Neuroblastoma is the most common pediatric neuroendocrine tumor. Patients with high-risk neuroblastoma have poor clinical outcomes. Understanding the mechanisms underlying neuroblastoma progression could help identify potential therapeutic targets. This study aimed to explore the roles of itchy E3 ubiquitin-protein ligase (ITCH) in neuroblastoma progression using neuroblastoma cell lines and xenograft models of neuroblastoma. [Methods] ITCH-silencing or overexpressing neuroblastoma cells were established using two different human neuroblastoma cell lines, SK-N-AS and SH-SY5Y. In vitro and in vivo experiments were carried out to determine the effects of ITCH on neuroblastoma cell behaviors. The dual-luciferase reporter assay and co-transfection experiments were applied to determine the interaction of ITCH and miR-145-5p during neuroblastoma progression. [Results] In both cell lines, ITCH overexpression significantly promotes the proliferation, migration, and invasion capacities of neuroblastoma cells, while ITCH silencing with ShITCH suppressed neuroblastoma cell proliferation and induced apoptosis. Moreover, overexpression of ITCH decreased 51% and 54% the protein expressions of large tumor suppressor kinase 1 (LATS1), and inhibited 59% and 66% the phosphorylation of Yes-associated protein (YAP), concomitant with 2.02-fold and 2.56-fold increased expressions of cell proliferation marker Ki67 and 2.51-fold and 2.26-fold elevated levels of anti-apoptosis marker Bcl2 in SK-N-AS and SH-SY5Y cells, respectively. The dual-luciferase reporter assay demonstrated that ITCH interacted with miR-145-5p. Further in vitro and xenograft experiments showed that ITCH negatively affected the tumor-suppressive effect of miR-145-5p. [Conclusion] ITCH promotes neuroblastoma cell proliferation and metastasis by inhibiting LATS1 and promoting YAP nuclear translocation.

scholarly journals Combined ALK and MDM2 inhibition increases antitumor activity and overcomes resistance in human ALK mutant neuroblastoma cell lines and xenograft models

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Hui Qin Wang ◽  
Ensar Halilovic ◽  
Xiaoyan Li ◽  
Jinsheng Liang ◽  
Yichen Cao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Human Neuroblastoma Cell ◽  
Wild Type ◽  
Combination Strategy ◽  
Human Neuroblastoma ◽  
Xenograft Models ◽  
Neuroblastoma Cell Lines

The efficacy of ALK inhibitors in patients with ALK-mutant neuroblastoma is limited, highlighting the need to improve their effectiveness in these patients. To this end, we sought to develop a combination strategy to enhance the antitumor activity of ALK inhibitor monotherapy in human neuroblastoma cell lines and xenograft models expressing activated ALK. Herein, we report that combined inhibition of ALK and MDM2 induced a complementary set of anti-proliferative and pro-apoptotic proteins. Consequently, this combination treatment synergistically inhibited proliferation of TP53 wild-type neuroblastoma cells harboring ALK amplification or mutations in vitro, and resulted in complete and durable responses in neuroblastoma xenografts derived from these cells. We further demonstrate that concurrent inhibition of MDM2 and ALK was able to overcome ceritinib resistance conferred by MYCN upregulation in vitro and in vivo. Together, combined inhibition of ALK and MDM2 may provide an effective treatment for TP53 wild-type neuroblastoma with ALK aberrations.

Sign in / Sign up

Export Citation Format

Share Document