scholarly journals Sulfated Glycosides from the Sea Cucumbers Block Ca2+ Flow in Murine Neuroblastoma Cells

2018 ◽  
Vol 13 (8) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Evgeny A. Pislyagin ◽  
Ekaterina S. Menchinskaya ◽  
Dmitry L. Aminin ◽  
Sergey A. Avilov ◽  
Alexandra S. Silchenko
Keyword(s):  
Cytotoxic Activity ◽  
Cellular Immunity ◽  
Immune Cells ◽  
Purinergic Receptors ◽  
Neuroblastoma Cells ◽  
Triterpene Glycosides ◽  
P2x7 Receptors ◽  
Sea Cucumbers ◽  
Scientific Task

Recently the ability of triterpene glycosides from sea cucumbers to interact with purinergic receptors of P2X family on the membranes of immune cells enhancing the reversible ATP-dependent Ca2+ intake and therefore modulating (stimulating) the receptor's activity was discovered. As a result the activation of cellular immunity on the organism level was observed. Purinergic receptors are associated with a series of important functions in normal and pathophysiology, thus the searching of its new modulators (both stimulants and blockers) seems to be very important medical and scientific task. The cytotoxic activity of four triterpene glycosides isolated from different species of sea cucumbers: liouvilloside A (1) from Pseudocolochirus violaceus, fallaxoside D1 (2) from Cucumaria fallax and magnumosides C3 (3) and C4 (4) from Massinium (=Neothynidium) magnum against neuroblastoma Neuro 2A cells was tested. The glycosides 1 and 4 were the most cytotoxic in the series (EC50 5.0 μM and 21.5 μM, correspondingly). Moreover, non-cytotoxic concentration (1 μM) of these compounds inhibited ATP-dependent Ca2+ intake into the Neuro 2A cells, containing P2X7 receptors on the surface, by 53 and 47%, correspondingly. The ability of sea cucumbers triterpene glycosides to block the purinergic receptors in vitro is first discovered.

scholarly journals Comparison of the proliferation, cytotoxic activity and cytokine secretion function of cascade primed immune cells and cytokine-induced killer cells in vitro

2015 ◽  
Vol 12 (2) ◽  
pp. 2629-2635 ◽  
Author(s):  
GUI-XIN LI ◽  
SHU-SHU ZHAO ◽  
XU-GUANG ZHANG ◽  
WEN-HAO WANG ◽  
JIN LIU ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Immune Cells ◽  
Cytokine Secretion ◽  
Killer Cells

scholarly journals Increased immune cell infiltration in patient-derived tumor explants treated with Traniplatin: an original Pt(iv) pro-drug based on Cisplatin and Tranilast

2018 ◽  
Vol 54 (60) ◽  
pp. 8324-8327 ◽  
Author(s):  
Daniele Lo Re ◽  
Diego Montagner ◽  
Dina Tolan ◽  
Claudio Di Sanza ◽  
Mar Iglesias ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Lung Cancer Cells ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Traniplatin shows increased in vitro cytotoxic activity against colon and lung cancer cells but decreased activity against immune cells in comparison to Cisplatin.

In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen

1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse
Keyword(s):  
Cell Differentiation ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Initial Value ◽  
Initial Rise ◽  
Biphasic Effect ◽  
Contrast Microscopy ◽  
Morphological Sign

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

Molecular iodine synergized and sensitized neuroblastoma cells to the antineoplastic effect of ATRA

2020 ◽  
Vol 27 (12) ◽  
pp. 699-710
Author(s):  
Irasema Mendieta ◽  
Gabriel Rodríguez-Gómez ◽  
Bertha Rueda-Zarazúa ◽  
Julia Rodríguez-Castelán ◽  
Winniberg Álvarez-León ◽  
...  
Keyword(s):  
Residual Disease ◽  
Neuroblastoma Cells ◽  
Survivin Expression ◽  
Body Weight Loss ◽  
Immunohistochemical Analysis ◽  
Molecular Iodine ◽  
Tyrosine Kinase Receptor ◽  
Adjuvant Effect

Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) is used as a treatment to decrease minimal residual disease. Molecular iodine (I2) induces differentiation and/or apoptosis in several neoplastic cells through activation of PPARγ nuclear receptors. Here, we analyzed whether the coadministration of I2 and ATRA increases the efficacy of NB treatment. ATRA-sensitive (SH-SY5Y), partially-sensitive (SK-N-BE(2)), and non-sensitive (SK-N-AS) NB cells were used to analyze the effect of I2 and ATRA in vitro and in xenografts (Foxn1 nu/nu mice), exploring actions on cellular viability, differentiation, and molecular responses. In the SH-SY5Y cells, 200 μM I2 caused a 100-fold (0.01 µM) reduction in the antiproliferative dose of ATRA and promoted neurite extension and neural marker expression (tyrosine hydroxylase (TH) and tyrosine kinase receptor alpha (Trk-A)). In SK-N-AS, the I2 supplement sensitized these cells to 0.1 μM ATRA, increasing the ATRA-receptor (RARα) and PPARγ expression, and decreasing the Survivin expression. The I2 supplement increased the mitochondrial membrane potential in SK-N-AS suggesting the participation of mitochondrial-mediated mechanisms involved in the sensibilization to ATRA. In vivo, oral I2 supplementation (0.025%) synergized the antitumor effect of ATRA (1.5 mg/kg BW) and prevented side effects (body weight loss and diarrhea episodes). The immunohistochemical analysis showed that I2 supplementation decreased the intratumoral vasculature (CD34). We suggest that the I2 + ATRA combination should be studied in preclinical and clinical trials to evaluate its potential adjuvant effect in addition to conventional treatments.

p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
Author(s):  
İrem Bozbey ◽  
Suat Sari ◽  
Emine Şalva ◽  
Didem Kart ◽  
Arzu Karakurt
Keyword(s):  
Molecular Modeling ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Modeling Studies ◽  
Broth Microdilution Method ◽  
Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents

2019 ◽  
Vol 19 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Faeze Khalili ◽  
Sara Akrami ◽  
Malihe Safavi ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Mina Saeedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
High Yield ◽  
Breast Cancer Cell Lines ◽  
Pyridine Derivatives ◽  
One Pot ◽  
Standard Drug ◽  
Three Component Reaction ◽  
Anti Cancer

Background: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives. Objective: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated. Methods: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death. Results: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods. Conclusion: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

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