Mesenchymal stem cell-derived exosomes suppress proliferation of T cells by inducing cell cycle arrest through p27kip1/Cdk2 signaling

2020 ◽  
Vol 225 ◽  
pp. 16-22 ◽  
Author(s):  
Sunho Lee ◽  
Sueon Kim ◽  
Hyunwoo Chung ◽  
Ji Hwan Moon ◽  
Seong Jun Kang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

scholarly journals Semi-purified extracts of Commelina benghalensis (Commelinaceae) induce apoptosis and cell cycle arrest in Jurkat-T cells

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Kgomotso Welheminah Lebogo ◽  
Matlou Phineas Mokgotho ◽  
Victor Patrick Bagla ◽  
Thabe Moses Matsebatlela ◽  
Vusi Mbazima ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Cycle Arrest ◽  
Jurkat T Cells ◽  
Commelina Benghalensis ◽  
Cycle Arrest

scholarly journals Glioblastoma Multiforme Stem Cell Cycle Arrest by Alkylaminophenol through the Modulation of EGFR and CSC Signaling Pathways

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 681 ◽  
Author(s):  
Phuong Doan ◽  
Aliyu Musa ◽  
Akshaya Murugesan ◽  
Vili Sipilä ◽  
Nuno R. Candeias ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Glioblastoma Multiforme ◽  
Cell Cycle Arrest ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Cell Population ◽  
Significant Role ◽  
Dependent Manner ◽  
Cycle Arrest

Cancer stem cells (CSCs), a small subpopulation of cells existing in the tumor microenvironment promoting cell proliferation and growth. Targeting the stemness of the CSC population would offer a vital therapeutic opportunity. 3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol (THTMP), a small synthetic phenol compound, is proposed to play a significant role in controlling the CSC proliferation and survival. We assessed the potential therapeutic effects of THTMP on glioblastoma multiforme (GBM) and its underlying mechanism in various signaling pathways. To fully comprehend the effect of THTMP on the CSCs, CD133+ GBM stem cell (GSC) and CD133- GBM Non-stem cancer cells (NSCC) population from LN229 and SNB19 cell lines was used. Cell cycle arrest, apoptosis assay and transcriptome analysis were performed for individual cell population. THTMP strongly inhibited NSCC and in a subtle way for GSC in a time-dependent manner and inhibit the resistance variants better than that of temozolomide (TMZ). THTMP arrest the CSC cell population at both G1/S and G2/M phase and induce ROS-mediated apoptosis. Gene expression profiling characterize THTMP as an inhibitor of the p53 signaling pathway causing DNA damage and cell cycle arrest in CSC population. We show that the THTMP majorly affects the EGFR and CSC signaling pathways. Specifically, modulation of key genes involved in Wnt, Notch and Hedgehog, revealed the significant role of THTMP in disrupting the CSCs’ stemness and functions. Moreover, THTMP inhibited cell growth, proliferation and metastasis of multiple mesenchymal patient-tissue derived GBM-cell lines. THTMP arrests GBM stem cell cycle through the modulation of EGFR and CSC signaling pathways.

scholarly journals Vasoactive Intestinal Peptide Induces Cell Cycle Arrest and Regulatory Functions in Human T Cells at Multiple Levels

2010 ◽  
Vol 30 (10) ◽  
pp. 2537-2551 ◽  
Author(s):  
Per Anderson ◽  
Elena Gonzalez-Rey
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Cycle Arrest ◽  
Vasoactive Intestinal Peptide ◽  
Molecular Mechanisms ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Experimental Models ◽  
Cycle Arrest ◽  
Human T Cells

ABSTRACT Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory neuropeptide that, by inhibiting Th1-driven responses and inducing the emergence of regulatory T cells (Treg), has been proven successful in the induction of tolerance in various experimental models of autoimmune disorders. Here, we investigate the molecular mechanisms involved in VIP-induced tolerance. VIP treatment in the presence of T-cell receptor (TCR) signaling and CD28 costimulation induced cell cycle arrest in human T cells. VIP blocked G1/S transition and inhibited the synthesis of cyclins D3 and E and the activation of the cyclin-dependent kinases (CDKs) cdk2 and cdk4. This effect was accompanied by maintenance of threshold levels of the CDK inhibitor p27kip1 and impairment of phosphatidylinositol 3-kinase (PI3K)-Akt signaling. Inhibition of interleukin 2 (IL-2) transcription and downregulation of signaling through NFAT, AP-1, and Ras-Raf paralleled the VIP-induced cell cycle arrest. Noteworthy from a functional point of view is the fact that VIP-treated T cells show a regulatory phenotype characterized by high expression of CD25, cytotoxic-T-lymphocyte-associated protein 4 (CTLA4), and Forkhead box protein 3 (FoxP3) and potent suppressive activities against effector T cells. CTLA4 appears to be critically involved in the generation and suppressive activities of VIP-induced Treg. Finally, cyclic AMP (cAMP) and protein kinase A (PKA) activation seems to mediate the VIP-induced cell cycle arrest and Treg generation.

Newly discovered role for Fas ligand in the cell-cycle arrest of CD4+ T cells

10.1038/3965 ◽  
1998 ◽  
Vol 4 (12) ◽  
pp. 1377-1382 ◽  
Author(s):  
Julie Desbarats ◽  
Richard C. Duke ◽  
M. Karen Newell
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Cycle Arrest ◽  
Cd4 T Cells ◽  
Fas Ligand ◽  
Cycle Arrest

A Secreted Low--Molecular-Weight Protein From Helicobacter pylori Induces Cell-Cycle Arrest of T Cells

2005 ◽  
Vol 128 (5) ◽  
pp. 1327-1339 ◽  
Author(s):  
Markus Gerhard ◽  
Christian Schmees ◽  
Petra Voland ◽  
Nicole Endres ◽  
Markus Sander ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Weight ◽  
T Cells ◽  
Helicobacter Pylori ◽  
Cell Cycle Arrest ◽  
Low Molecular Weight ◽  
Molecular Weight Protein ◽  
Cycle Arrest ◽  
Weight Protein ◽  
Low Molecular Weight Protein

scholarly journals Protein Kinase A Phosphorylation Activates Vpr-Induced Cell Cycle Arrest during Human Immunodeficiency Virus Type 1 Infection

2010 ◽  
Vol 84 (13) ◽  
pp. 6410-6424 ◽  
Author(s):  
R. Anthony Barnitz ◽  
Fengyi Wan ◽  
Vinay Tripuraneni ◽  
Diane L. Bolton ◽  
Michael J. Lenardo
Keyword(s):  
Cell Cycle ◽  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Protein Kinase ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Kinase A

ABSTRACT Infection with human immunodeficiency virus type 1 (HIV-1) causes an inexorable depletion of CD4+ T cells. The loss of these cells is particularly pronounced in the mucosal immune system during acute infection, and the data suggest that direct viral cytopathicity is a major factor. Cell cycle arrest caused by the HIV-1 accessory protein Vpr is strongly correlated with virus-induced cell death, and phosphorylation of Vpr serine 79 (S79) is required to activate G2/M cell cycle blockade. However, the kinase responsible for phosphorylating Vpr remains unknown. Our bioinformatic analyses revealed that S79 is part of a putative phosphorylation site recognized by protein kinase A (PKA). We show here that PKA interacts with Vpr and directly phosphorylates S79. Inhibition of PKA activity during HIV-1 infection abrogates Vpr cell cycle arrest. These findings provide new insight into the signaling event that activates Vpr cell cycle arrest, ultimately leading to the death of infected T cells.

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