scholarly journals Perphenazine and Prochlorperazine Decrease Glioblastoma U87-MG Cells Migration and Invasion: Analysis of the ABCB1 and ABCG2 Transporters, E-Cadherin, α-Tubulin, and Integrins (α3, α5, and β1) Levels.

2021 ◽  
Author(s):  
Michał Otręba ◽  
Jerzy Stojko ◽  
Agata Kabała-Dzik ◽  
Anna Rzepecka-Stojko
Keyword(s):  
Multidrug Resistance ◽  
Crucial Role ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Main Role ◽  
Multidrug Resistance Proteins ◽  
Phenothiazine Derivatives ◽  
Human Glioblastoma ◽  
The Impact ◽  
E Cadherin

Abstract Purpose: Glioblastoma multiforme is the most frequent malignant brain tumor as well as one of the most lethal and untreatable human tumors with a very poor survival rate. Thus, novel and effective strategies of treatment are required. Integrins play a crucial role in the regulation of cellular adhesion and invasion. Moreover, integrins and alpha-tubulin are very important in cell migration, while E-cadherin plays the main role in tumor metastasis. Their ability to penetrate the BBB and signs of intracerebral activity are very important in glioblastoma therapy. ABC transporters ABCB1 and ABCG2, which are localized in the brain endothelial capillaries of BBB, play a crucial role in the development of multidrug resistance, and are modulated by phenothiazine derivatives. Methods: The impact on the motility of human glioblastoma U87-MG was evaluated with a wound healing assay; cellular migration, and invasion by the transwell assay, while ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins content was determined with the Western blot.Results: This study explores the effect of perphenazine and prochlorperazine on ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins (α3, α5, and β1) amount as well as on migration and invasion ability of human glioblastoma (U87-MG) cells. The results suggest that perphenazine and prochlorperazine modulate multidrug resistance proteins (they decrease ABCB1 and increase ABCG2), E-cadherin, α-tubulin, and integrins amount as well as impair migration and invasion of the U87-MG cell line. Conclusions: The decrease of migration and invasion ability after phenothiazine derivatives treatment due to the increase of ABCG2 and E-cadherin as well as the decrease of α-tubulin, and integrins amounts can support the hypothesis that perphenazine and prochlorperazine have the anticancer effect on human glioblastoma U87-MG cells.

Perphenazine And Prochlorperazine Decrease Glioblastoma Cells Migration And Invasion: Analysis of ABCB1 And ABCG2 Transporters, e-cadherin, α-tubulin, And Integrins (α3, α5, and β1) Expression in U87-MG Cells

2021 ◽  
Author(s):  
Michał Otręba ◽  
Jerzy Stojko ◽  
Agata Kabała-Dzik ◽  
Anna Rzepecka-Stojko
Keyword(s):  
Multidrug Resistance ◽  
Cancer Metastasis ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Multidrug Resistance Proteins ◽  
Phenothiazine Derivatives ◽  
Human Glioblastoma ◽  
Anticancer Chemotherapy ◽  
The Impact ◽  
E Cadherin

Abstract Purpose: Glioblastoma multiforme is the most frequent malignant brain tumor as well as one of the most lethal and untreatable human tumors with a very poor survival rate (up to 18 months). Thus, novel and effective strategies of treatment are still required since resistance and metastasis are major problems of anticancer chemotherapy. Interestingly, ABC transporters, which play a crucial role in the development of multidrug resistance, are modulated by phenothiazine derivatives, while cancer metastasis, migration, and invasion are regulated by cadherins, α-tubulin, and integrins. Methods: The impact on the motility of human glioblastoma U87-MG was performed by wound healing assay, cellular migration and invasion were performed by transwell assay, while ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins (α3, α5, and β1) content were determined by Western blot.Results: The present study explores the effect of perphenazine and prochlorperazine on ABCB1, ABCG2, E-cadherin, α-tubulin, and integrins (α3, α5, and β1) amount as well as migration and invasion ability of human glioblastoma (U87-MG) cells suggesting that phenothiazine derivatives impair multidrug resistance proteins (ABCB1 and ABCG2), E-cadherin, α-tubulin, and integrins amount as well as impair migration and invasion of the U87-MG cell line. Conclusions: The study demonstrated that an increase of ABCG2 and E-cadherin as well as a decrease of α-tubulin, and integrins amount may explain the decrease of migration and invasion ability after phenothiazine derivatives treatment. Moreover, only prochlorperazine significantly reduces the rate of cell migration. Thus, the drug may be considered for the development of new and effective glioblastoma therapy.

scholarly journals Magnolol Suppresses Pancreatic Cancer Development In Vivo and In Vitro via Negatively Regulating TGF-β/Smad Signaling

2020 ◽  
Vol 10 ◽  
Author(s):  
Shuo Chen ◽  
Jiaqi Shen ◽  
Jing Zhao ◽  
Jiazhong Wang ◽  
Tao Shan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cellular Migration ◽  
Growth Effect ◽  
Migration And Invasion ◽  
Therapeutic Drug ◽  
Antitumor Effects ◽  
Mesenchymal Transition ◽  
E Cadherin

Magnolol, a hydroxylated biphenyl extracted from Magnolia officinalis, has recently drawn attention due to its anticancer potential. The present study was aimed to explore the effects of Magnolol on restraining the proliferation, migration and invasion of pancreatic cancer in vivo and in vitro. Magnolol showed significant anti-growth effect in an orthotopic xenograft nude mouse model, and immunohistochemical staining of the xenografts revealed that Magnolol suppressed vimentin expression and facilitated E-cadherin expression. The cytoactive detection using CCK-8 assay showed Magnolol inhibited PANC-1 and AsPC-1 concentration-dependently. Scratch healing assay and the Transwell invasion assay proved the inhibiting effects of Magnolol on cellular migration and invasion at a non-cytotoxic concentration. Western blot and rt-PCR showed that Magnolol suppressed epithelial-mesenchymal-transition by increasing the expression level of E-cadherin and decreasing those of N-cadherin and vimentin. Magnolol suppressed the TGF-β/Smad pathway by negatively regulating phosphorylation of Smad2/3. Moreover, TGF-β1 impaired the antitumor effects of Magnolol in vivo. These results demonstrated that Magnolol can inhibit proliferation, migration and invasion in vivo and in vitro by suppressing the TGF-β signal pathway and EMT. Magnolol could be a hopeful therapeutic drug for pancreatic malignancy.

Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia

2001 ◽  
Vol 120 (5) ◽  
pp. A93-A93
Author(s):  
D ROST ◽  
J KONIG ◽  
G WEISS ◽  
E KLAR ◽  
W STREMMEL ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistance Proteins ◽  
Human Gallbladder ◽  
Resistance Proteins

scholarly journals HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Chun Cheng ◽  
Jun Yang ◽  
Si-Wei Li ◽  
Guofu Huang ◽  
Chenxi Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Therapeutic Target ◽  
Histone Deacetylases ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractHistone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.

scholarly journals Microgravity Induces Transient EMT in Human Keratinocytes by Early Down-Regulation of E-Cadherin and Cell-Adhesion Remodeling

2020 ◽  
Vol 11 (1) ◽  
pp. 110
Author(s):  
Giulia Ricci ◽  
Alessandra Cucina ◽  
Sara Proietti ◽  
Simona Dinicola ◽  
Francesca Ferranti ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Human Keratinocytes ◽  
Short Exposure ◽  
Migration And Invasion ◽  
Hacat Cells ◽  
Invasive Phenotype ◽  
Adhesion Properties ◽  
Mesenchymal Transition ◽  
Cell Matrix ◽  
E Cadherin

Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promotes an early epithelial–mesenchymal transition (EMT). Herein, we developed this investigation to verify if the cells maintain the acquired invasive phenotype after an extended period of weightlessness exposure. We also evaluated cells’ capability in recovering epithelial characteristics when seeded again into a normal gravitational field after short microgravity exposure. We evaluated the ultra-structural junctional features of HaCaT cells by Transmission Electron Microscopy and the distribution pattern of vinculin and E-cadherin by confocal microscopy, observing a rearrangement in cell–cell and cell–matrix interactions. These results are mirrored by data provided by migration and invasion biological assay. Overall, our studies demonstrate that after extended periods of microgravity, HaCaT cells recover an epithelial phenotype by re-establishing E-cadherin-based junctions and cytoskeleton remodeling, both being instrumental in promoting a mesenchymal–epithelial transition (MET). Those findings suggest that cytoskeletal changes noticed during the first weightlessness period have a transitory character, given that they are later reversed and followed by adaptive modifications through which cells miss the acquired mesenchymal phenotype.

scholarly journals Jinlong capsule inhibits migration and invasion in human glioblastoma cells via the modulation of mTOR/S6 signaling pathway

2019 ◽  
Vol Volume 13 ◽  
pp. 1023-1032 ◽  
Author(s):  
Jingren Shi ◽  
Wenli Zhang ◽  
Lu He ◽  
Fanhong Kong ◽  
Meichen Pan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Migration And Invasion ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cells

scholarly journals Cooperation/Competition between Halogen Bonds and Hydrogen Bonds in Complexes of 2,6-Diaminopyridines and X-CY3 (X = Cl, Br; Y = H, F)

Symmetry ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 766
Author(s):  
Barbara Bankiewicz ◽  
Marcin Palusiak
Keyword(s):  
Complex Formation ◽  
Hydrogen Bonds ◽  
Dft Calculations ◽  
Electrostatic Interactions ◽  
Dipole Moments ◽  
Main Role ◽  
Halogen Bonds ◽  
Topological Parameters ◽  
Leading Role ◽  
The Impact

The DFT calculations have been performed on a series of two-element complexes formed by substituted 2,6-diaminopyridine (R−PDA) and pyridine (R−Pyr) with X−CY3 molecules (where X = Cl, Br and Y = H, F). The primary aim of this study was to examine the intermolecular hydrogen and halogen bonds in the condition of their mutual coexistence. Symmetry/antisymmetry of the interrelation between three individual interactions is addressed. It appears that halogen bonds play the main role in the stabilization of the structures of the selected systems. However, the occurrence of one or two hydrogen bonds was associated with the favourable geometry of the complexes. Moreover, the impact of different substituent groups attached in the para position to the aromatic ring of the 2,6-diaminopyridine and pyridine on the character of the intermolecular hydrogen and halogen bonds was examined. The results indicate that the presence of electron-donating substituents strengthens the bonds. In turn, the presence of electron-withdrawing substituents reduces the strength of halogen bonds. Additionally, when hydrogen and halogen bonds lose their leading role in the complex formation, the nonspecific electrostatic interactions between dipole moments take their place. Analysis was based on geometric, energetic, and topological parameters of the studied systems.

scholarly journals Identification of PIM1 substrates reveals a role for NDRG1 phosphorylation in prostate cancer cellular migration and invasion

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Russell J. Ledet ◽  
Sophie E. Ruff ◽  
Yu Wang ◽  
Shruti Nayak ◽  
Jeffrey A. Schneider ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Invasion And Metastasis ◽  
Serine Threonine Kinase ◽  
Prostate Tumorigenesis ◽  
Threonine Kinase ◽  
Chemical Genetic ◽  
Protein Levels

AbstractPIM1 is a serine/threonine kinase that promotes and maintains prostate tumorigenesis. While PIM1 protein levels are elevated in prostate cancer relative to local disease, the mechanisms by which PIM1 contributes to oncogenesis have not been fully elucidated. Here, we performed a direct, unbiased chemical genetic screen to identify PIM1 substrates in prostate cancer cells. The PIM1 substrates we identified were involved in a variety of oncogenic processes, and included N-Myc Downstream-Regulated Gene 1 (NDRG1), which has reported roles in suppressing cancer cell invasion and metastasis. NDRG1 is phosphorylated by PIM1 at serine 330 (pS330), and the level of NDRG1 pS330 is associated higher grade prostate tumors. We have shown that PIM1 phosphorylation of NDRG1 at S330 reduced its stability, nuclear localization, and interaction with AR, resulting in enhanced cell migration and invasion.

scholarly journals Survivin drives tumor-associated macrophage reprogramming: a novel mechanism with potential impact for obesity

2021 ◽  
Author(s):  
E. Benaiges ◽  
V. Ceperuelo-Mallafré ◽  
A. Madeira ◽  
R. Bosch ◽  
C. Núñez-Roa ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Expression Patterns ◽  
Intracellular Localization ◽  
Immunohistochemical Analysis ◽  
Subcellular Fractionation ◽  
Migration And Invasion ◽  
Macrophage Phenotype ◽  
Tumor Associated Macrophages ◽  
Obesity And Cancer ◽  
The Impact

Abstract Purpose Recent studies point to adipose-derived stem cells (ASCs) as a link between obesity and cancer. We aimed to determine whether survivin, which is highly secreted by ASCs from subjects with obesity, might drive a pro-tumoral phenotype in macrophages. Methods The effect of ASC conditioned medium on the macrophage phenotype was assessed by expression studies. Survivin intracellular localization and internalization were examined by subcellular fractionation and immunofluorescence, respectively. Loss- and gain-of-function studies were performed using adenoviral vectors, and gene expression patterns, migration and invasion capacities of cancer cells were examined. Heterotypic cultures of ASCs, macrophages and cancer cells were established to mimic the tumor microenvironment. Survivin-blocking experiments were used to determine the impact of survivin on both macrophages and cancer cells. Immunohistochemical analysis of survivin was performed in macrophages from ascitic fluids of cancer patients and healthy controls. Results We found that obese-derived ASCs induced a phenotypic switch in macrophages characterized by the expression of both pro- and anti-inflammatory markers. Macrophages were found to internalize extracellular survivin, generating hybrid macrophages with a tumor-associated phenotype that included secretion of survivin. Exogenous expression of survivin in macrophages generated a similar phenotype and enhanced the malignant characteristics of cancer cells by a mechanism dependent on survivin phosphorylation at threonine 34. Survivin secreted by both ASCs from subjects with obesity and tumor-associated macrophages synergistically boosted the malignancy of cancer cells. Importantly, survivin was mainly detected in ascites-associated macrophages from patients with a malignant diagnosis. Conclusion Our data indicate that survivin may serve as a molecular link between obesity and cancer and as a novel marker for tumor-associated macrophages.

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