scholarly journals Targeting Aryl Hydrocarbon Receptor with small molecule, 1′H-indole-3′-carbonyl-thiazole-4-carboxylic acid methyl ester blocked human glioma cell invasion via MYH9

2020 ◽  
Author(s):  
Lijiao Zhao ◽  
Qiuting Shu ◽  
Hui Sun ◽  
Yunlong Ma ◽  
Dandan Kang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Carboxylic Acid ◽  
Methyl Ester ◽  
Glioma Cell ◽  
Acid Methyl Ester ◽  
Glioma Cells ◽  
Human Glioma ◽  
Aryl Hydrocarbon ◽  
Acid Methyl ◽  
Glioma Cell Migration

AbstractAryl hydrocarbon receptor (AHR) was a master regulator of anti-tumor cell migration in various cell types. Whether and how AHR regulates glioma cell migration is largely unknown. We found that small molecule 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous AHR ligand, can significantly block glioma cell migration and invasion in vitro, ex vivo and in vivo. Knocking down AHR by siRNA abolished ITE’s migration-inhibiting effects. ITE increased the number of filopodia-like protrusion formation, but reduced protrusion attachment to the extracellular matrix, and inhibited the rear retraction of migrating glioma cells. Moreover, both mesenchymal and amoeboid migrating cells were observed in the DMSO control group while none of the cells display amoeboid migration in the ITE treated group. MYH9 was significantly reduced by ITE treatment in human glioma cells. Over-expression of MYH9 abrogated ITE’s migration-inhibiting effects, with the expression level of MYH9 correlated with cell migration ability. Since MYH9 is a component of non-muscle myosin IIA (NMIIA), which is essential for cell migration in 3D confined space, and not a discovered target of AHR, the fact that ITE affects MYH9 via AHR opens a new research and development avenue.

scholarly journals 1′H-Indole-3′-Carbonyl-Thiazole-4-Carboxylic Acid Methyl Ester Blocked Human Glioma Cell Invasion via Aryl Hydrocarbon Receptor’s Regulation of Cytoskeletal Contraction

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Lijiao Zhao ◽  
Qiuting Shu ◽  
Hui Sun ◽  
Yunlong Ma ◽  
Dandan Kang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Carboxylic Acid ◽  
Methyl Ester ◽  
Cell Invasion ◽  
Glioma Cell ◽  
Acid Methyl Ester ◽  
Confined Space ◽  
Aryl Hydrocarbon ◽  
Acid Methyl

Blocking glioma cell invasion has been challenging due to cancer cells that can swiftly switch their migration mode, and agents that can block more than one migration mode are sought after. We found that small molecule 2-(1H-indole-3-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous aryl hydrocarbon receptor (AHR) agonist, can block more than one mode of glioma cell migration, based on cultured cell behavior captured by videos. Data from wound-healing assays and mouse xenograft glioma models corroborated ITE’s migration-inhibiting effects while knocking down AHR by siRNA abolished these effects. To identify genes that mediated ITE-AHR’s effect, we first collected gene expression changes upon ITE treatment by RNA-seq, then compared them against literature reported migration-related genes in glioma and that were potentially regulated by AHR. MYH9, a component of nonmuscle myosin IIA (NMIIA), was confirmed to be reduced by ITE treatment. When MYH9 was overexpressed in the glioma cells, a good correlation was observed between the expression level and the cell migration ability, determined by wound-healing assay. Correspondingly, overexpression of MYH9 abrogated ITE’s migration-inhibiting effects, indicating that ITE-AHR inhibited cell migration via inhibiting MYH9 expression. MYH9 is essential for cell migration in 3D confined space and not a discovered target of AHR; the fact that ITE affects MYH9 via AHR opens a new research and development avenue.

Induction of glioma cell migration by vitronectin in human serum and cerebrospinal fluid

2007 ◽  
Vol 107 (3) ◽  
pp. 578-585 ◽  
Author(s):  
Yuji Fukushima ◽  
Masakazu Tamura ◽  
Hidemitsu Nakagawa ◽  
Kazuyuki Itoh
Keyword(s):  
Cerebrospinal Fluid ◽  
Cell Migration ◽  
Healthy Volunteers ◽  
Human Serum ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Heat Inactivation ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Glioma Cell Migration

Object Malignant gliomas are often highly invasive and can migrate along blood vessels. The purpose of the current study was to identify the substance in human serum and/or cerebrospinal fluid (CSF) that promotes glioma cell migration. Methods The authors used a Boyden chamber cell migration assay to study the effect of serum from patients with glioma and healthy volunteers on chemotaxis of A172 human glioma cells. Heat inactivation, trypsinization, and ultra-filtration of serum were used to establish the nature of the active factor. Vitronectin and fibronectin were chosen for further investigations; chemotactic effects were studied in both serum and CSF. Results Serum from both patients with glioma and healthy volunteers was found to promote chemotaxis of human glioma cells. This activity was greatly reduced by heat inactivation or trypsinization. Fractionation of the serum by ultrafiltration through membranes with various pore sizes showed that the active molecule was larger than 50 kD. Antibodies against integrin αv or αvβ5 or arginine-glycine-aspartic acid–containing peptides, both of which block the vitronectin–glioma cell interactions, significantly reduced serum-induced cell migration, whereas blocking the interaction of glioma cells with fibronectin had no effect. Furthermore, the ability of serum to promote the migration of A172 or T98G glioma cells was suppressed by immunodepletion of vitronectin and restored by the addition of exogenous vitronectin. The migration of glioma cells induced by CSF collected from the postoperative cavity of a malignant glioma patient was also reduced by blocking the interaction of glioma cells with vitronectin. Conclusions These results suggest that vitronectin is one of the major factors in serum- and CSF-induced glioma cell migration.

scholarly journals Thermodynamic Properties of Three Pyridine Carboxylic Acid Methyl Ester Isomers

2007 ◽  
Vol 52 (2) ◽  
pp. 580-585 ◽  
Author(s):  
Maria D. M. C. Ribeiro da Silva ◽  
Vera L. S. Freitas ◽  
Luís M. N. B. F. Santos ◽  
Michal Fulem ◽  
M. J. Sottomayor ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Methyl Ester ◽  
Thermodynamic Properties ◽  
Acid Methyl Ester ◽  
Pyridine Carboxylic Acid ◽  
Acid Methyl ◽  
Pyridine Carboxylic

scholarly journals Regulation of human glioma cell migration, tumor growth, and stemness gene expression using a Lck targeted inhibitor

Oncogene ◽  
2018 ◽  
Vol 38 (10) ◽  
pp. 1734-1750 ◽  
Author(s):  
J. P. Zepecki ◽  
K. M. Snyder ◽  
M. M. Moreno ◽  
E. Fajardo ◽  
A. Fiser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Tumor Growth ◽  
Glioma Cell ◽  
Human Glioma ◽  
Human Glioma Cell ◽  
Glioma Cell Migration

3β-(4-Ethyl-3-iodophenyl)nortropane-2β- carboxylic Acid Methyl Ester as a High-Affinity Selective Ligand for the Serotonin Transporter

1997 ◽  
Vol 40 (24) ◽  
pp. 3861-3864 ◽  
Author(s):  
Bruce E. Blough ◽  
Philip Abraham ◽  
Andrew C. Mills ◽  
Anita H. Lewin ◽  
John W. Boja ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Methyl Ester ◽  
Serotonin Transporter ◽  
Acid Methyl Ester ◽  
High Affinity ◽  
Acid Methyl ◽  
Selective Ligand

3β-(p-Trimethylsilylphenyl)tropane-2β-carboxylic acid methyl ester: A new precursor for the preparation of [123I]RTI-55

1996 ◽  
Vol 47 (1) ◽  
pp. 79-81 ◽  
Author(s):  
John L. Musachio ◽  
Kathryn I. Keverline ◽  
F.Ivy Carroll ◽  
Robert F. Dannals
Keyword(s):  
Carboxylic Acid ◽  
Methyl Ester ◽  
Acid Methyl Ester ◽  
Acid Methyl

Selective induced polarization through electron transfer in acetone and pyrazole ester derivatives via C–H⋯OC interaction

2014 ◽  
Vol 38 (10) ◽  
pp. 4885-4892 ◽  
Author(s):  
Ashish Kumar Tewari ◽  
Priyanka Srivastava ◽  
Ved P. Singh ◽  
Praveen Singh ◽  
Ranjeet Kumar ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Carboxylic Acid ◽  
Methyl Ester ◽  
Organic Compounds ◽  
Acid Methyl Ester ◽  
Induced Polarization ◽  
Acetone Molecule ◽  
Acid Methyl

A set of organic compounds (pyrazole ester derivatives,viz.5-[3-(substituted)-propoxy]-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester and 5-[2-(substituted)-ethoxy]-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester) was synthesized and their affinity and stability towards the acetone molecule were tested by NMR.

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