scholarly journals Glucosamine induces cell-cycle arrest and hypertrophy of mesangial cells: implication of gangliosides

2005 ◽  
Vol 388 (2) ◽  
pp. 537-544 ◽  
Author(s):  
Elodie MASSON ◽  
Nicolas WIERNSPERGER ◽  
Michel LAGARDE ◽  
Samer El BAWAB
Keyword(s):  
Cell Cycle ◽  
Diabetic Nephropathy ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Mesangial Cell ◽  
Kinase Inhibitor ◽  
Mesangial Cells ◽  
Potential Implication ◽  
Cycle Arrest ◽  
Hexosamine Pathway

Alterations in proliferation and hypertrophy of renal mesangial cells are typical features of diabetic nephropathy. The HP (hexosamine pathway) has been proposed as a biochemical hypothesis to explain microvascular alterations due to diabetic nephropathy; however, involvement of HP in the regulation of mesangial cell growth or hypertrophy has been poorly studied. Although gangliosides are known to regulate cell proliferation, their potential role in mesangial cell-growth perturbations has hardly been explored. In the present study, we investigated the effects of the HP activation, mimicked by GlcN (glucosamine) treatment, on mesangial cell growth and hypertrophy and the potential implication of gangliosides in these processes. Our results indicate that GlcN induced hypertrophy of mesangial cells, as measured by an increase in the protein/cell ratio, and it caused cell-cycle arrest by an increase in the expression of cyclin-dependent kinase inhibitor p21Waf1/Cip1. Furthermore, GlcN treatment resulted in a massive increase in the levels of gangliosides GM2 and GM1. Treatment of cells with exogenous GM2 and GM1 reproduced the effects of 0.5 mM GlcN on p21Waf1/Cip1 expression, cell-cycle arrest and hypertrophy, suggesting that gangliosides GM2 and GM1 are probably involved in mediating GlcN effects. These results document a new role of the HP in the regulation of mesangial cell growth and hypertrophy. They also suggest a potential new mechanism of action of the HP through modulation of ganglioside levels.

Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome

2020 ◽  
Vol 19 (16) ◽  
pp. 2019-2033 ◽  
Author(s):  
Pratibha Pandey ◽  
Mohammad H. Siddiqui ◽  
Anu Behari ◽  
Vinay K. Kapoor ◽  
Kumudesh Mishra ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Gall Bladder ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Gall Bladder Cancer ◽  
Cell Growth Inhibition ◽  
Cycle Arrest ◽  
Apoptotic Induction

Background: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. Objective: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. Methods: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. Results: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5μM) in combination with Jab1-siRNA. Conclusion: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of gall bladder cancer.

scholarly journals ei24, a p53 Response Gene Involved in Growth Suppression and Apoptosis

2000 ◽  
Vol 20 (1) ◽  
pp. 233-241 ◽  
Author(s):  
Zhengming Gu ◽  
Cathy Flemington ◽  
Thomas Chittenden ◽  
Gerard P. Zambetti
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Apoptotic Cell ◽  
Functional Characterization ◽  
Growth Control ◽  
P53 Tumor Suppressor ◽  
Cycle Arrest ◽  
P53 Response

ABSTRACT DNA damage and/or hyperproliferative signals activate the wild-type p53 tumor suppressor protein, which induces a G1 cell cycle arrest or apoptosis. Although the mechanism of p53-mediated cell cycle arrest is fairly well defined, the p53-dependent pathway regulating apoptosis is poorly understood. Here we report the functional characterization of murine ei24 (also known asPIG8), a gene directly regulated by p53, whose overexpression negatively controls cell growth and induces apoptotic cell death. Ectopic ei24 expression markedly inhibits cell colony formation, induces the morphological features of apoptosis, and reduces the number of β-galactosidase-marked cells, which is efficiently blocked by coexpression of Bcl-XL. Theei24/PIG8 gene is localized on human chromosome 11q23, a region frequently altered in human cancers. These results suggest that ei24 may play an important role in negative cell growth control by functioning as an apoptotic effector of p53 tumor suppressor activities.

scholarly journals Mitogen-Activated Protein Kinase Hog1 Mediates Adaptation to G1 Checkpoint Arrest during Arsenite and Hyperosmotic Stress

2008 ◽  
Vol 7 (8) ◽  
pp. 1309-1317 ◽  
Author(s):  
Iwona Migdal ◽  
Yulia Ilina ◽  
Markus J. Tamás ◽  
Robert Wysocki
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cell Cycle Arrest ◽  
Kinase Inhibitor ◽  
Hyperosmotic Stress ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
Cycle Arrest ◽  
Mitogen Activated Protein

ABSTRACT Cells slow down cell cycle progression in order to adapt to unfavorable stress conditions. Yeast (Saccharomyces cerevisiae) responds to osmotic stress by triggering G1 and G2 checkpoint delays that are dependent on the mitogen-activated protein kinase (MAPK) Hog1. The high-osmolarity glycerol (HOG) pathway is also activated by arsenite, and the hog1Δ mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1Δ cells. Yeast cell cycle regulation in response to arsenite and the role of Hog1 in this process have not yet been analyzed. Here, we found that long-term exposure to arsenite led to transient G1 and G2 delays in wild-type cells, whereas cells that lack the HOG1 gene or are defective in Hog1 kinase activity displayed persistent G1 cell cycle arrest. Elevated levels of intracellular arsenite and “cross talk” between the HOG and pheromone response pathways, observed in arsenite-treated hog1Δ cells, prolonged the G1 delay but did not cause a persistent G1 arrest. In contrast, deletion of the SIC1 gene encoding a cyclin-dependent kinase inhibitor fully suppressed the observed block of G1 exit in hog1Δ cells. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1Δ cells. Interestingly, Sic1-dependent persistent G1 arrest was also observed in hog1Δ cells during hyperosmotic stress. Taken together, our data point to an important role of the Hog1 kinase in adaptation to stress-induced G1 cell cycle arrest.

Inhibition of cell growth and induction of G1-phase cell cycle arrest in hepatoma cells by steroid extract from Meretrix meretrix

2006 ◽  
Vol 232 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Ting-He Wu ◽  
Ruo-Lin Yang ◽  
Li-Ping Xie ◽  
Hong-Zhong Wang ◽  
Lei Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Hepatoma Cells ◽  
Phase Cell ◽  
G1 Phase ◽  
Meretrix Meretrix ◽  
Cycle Arrest

scholarly journals MiR-140-5p suppresses retinoblastoma cell growth via inhibiting c-Met/AKT/mTOR pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yujun Liao ◽  
Xiaolong Yin ◽  
Yan Deng ◽  
Xiaowei Peng
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Large Set ◽  
Retinoblastoma Cell ◽  
Cycle Arrest ◽  
Potential Biomarker ◽  
N Classification ◽  
Mirnas Expression ◽  
T Classification

MiR-140-5p is low expression and acts as a tumor suppressor in various types of human cancers. However, the potential role of miR-140-5p in retinoblastoma (RB) remains unknown. In the present study, we performed the miRNA microarray analysis to investigate whether miRNAs expression are associated with RB tumorigenesis in RB tissues. We found that a large set of miRNAs were ectopic expressions and miR-140-5p is most significantly down-regulated in human RB tissues compared with normal retinas. In addition, low miR-140-5p expression is associated with clinicopathological features (differentiation, invasion, T classification, N classification, cTNM stage, and largest tumor base) and poor survival in RB patients. Furthermore, our results showed that overexpression of miR-140-5p suppresses proliferation and induces apoptosis and cell cycle arrest in RB cell. Meanwhile, we confirmed that c-Met is the functional target of miR-140-5p in RB cell, and miR-140-5p expression is negatively correlated with c-Met in RB tissues. We also found that inhibition of c-Met also suppresses proliferation and induces apoptosis and cell cycle arrest in RB cell. Interestingly, c-Met can rescue the suppressive effects of miR-140-5p on RB cell growth and cell cycle arrest. More importantly, our findings indicated that miR-140-5p may inhibit cell growth via blocking c-Met/AKT/mTOR signaling pathway. Collectively, these results suggested that miR-140-5p might be a potential biomarker and target in the diagnosis and treatment of RB.

E4F1 silencing inhibits the cell growth through cell‐cycle arrest in malignant transformed cells induced by hydroquinone

2018 ◽  
Vol 33 (4) ◽  
pp. e22269 ◽  
Author(s):  
Qiang Tan ◽  
Jieyou Li ◽  
Jianming Peng ◽  
Zhidong Liu ◽  
Jiaxian Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Transformed Cells ◽  
Cycle Arrest

12-Deoxyphorbol 13-palmitate mediated cell growth inhibition, G2-M cell cycle arrest and apoptosis in BGC823 cells

2013 ◽  
Vol 700 (1-3) ◽  
pp. 13-22 ◽  
Author(s):  
Hui-Yu Xu ◽  
Zhi-Wei Chen ◽  
He Li ◽  
Li Zhou ◽  
Feng Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Cell Growth Inhibition ◽  
M Cell ◽  
Cycle Arrest

scholarly journals Growth Suppression by Acute PromyelocyticLeukemia-Associated Protein PLZF Is Mediated by Repression ofc-mycExpression

2003 ◽  
Vol 23 (24) ◽  
pp. 9375-9388 ◽  
Author(s):  
Melanie J. McConnell ◽  
Nathalie Chevallier ◽  
Windy Berkofsky-Fessler ◽  
Jena M. Giltnane ◽  
Rupal B. Malani ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Target Genes ◽  
Ectopic Expression ◽  
Growth Suppression ◽  
Quiescent State ◽  
Cycle Arrest

ABSTRACT The transcriptional repressor PLZF was identified by its translocation with retinoic acid receptor alpha in t(11;17) acute promyelocytic leukemia (APL). Ectopic expression of PLZF leads to cell cycle arrest and growth suppression, while disruption of normal PLZF function is implicated in the development of APL. To clarify the function of PLZF in cell growth and survival, we used an inducible PLZF cell line in a microarray analysis to identify the target genes repressed by PLZF. One prominent gene identified was c-myc. The array analysis demonstrated that repression of c-myc by PLZF led to a reduction in c-myc-activated transcripts and an increase in c-myc-repressed transcripts. Regulation of c-myc by PLZF was shown to be both direct and reversible. An interaction between PLZF and the c-myc promoter could be detected both in vitro and in vivo. PLZF repressed the wild-type c-myc promoter in a reporter assay, dependent on the integrity of the binding site identified in vitro. PLZF binding in vivo was coincident with a decrease in RNA polymerase occupation of the c-myc promoter, indicating that repression occurred via a reduction in the initiation of transcription. Finally, expression of c-myc reversed the cell cycle arrest induced by PLZF. These data suggest that PLZF expression maintains a cell in a quiescent state by repressing c-myc expression and preventing cell cycle progression. Loss of this repression through the translocation that occurs in t(11;17) would have serious consequences for cell growth control.

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