Selective Antisense Oligonucleotide Inhibition of Human IRF4 Prevents Malignant Myeloma Regeneration Via Cell Cycle Disruption

2020 ◽  
Author(s):  
Phoebe K. Mondala ◽  
Ashni A. Vora ◽  
Tianyuan Zhou ◽  
Elisa Lazzari ◽  
Luisa Ladel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antisense Oligonucleotide ◽  
Cell Cycle Disruption

scholarly journals Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption

2021 ◽  
Author(s):  
Phoebe K. Mondala ◽  
Ashni A. Vora ◽  
Tianyuan Zhou ◽  
Elisa Lazzari ◽  
Luisa Ladel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antisense Oligonucleotide ◽  
Cell Cycle Disruption

Neurotoxicity of zearalenone’s metabolites and beauvericin mycotoxins via apoptosis and cell cycle disruption

Toxicology ◽  
2021 ◽  
pp. 152784
Author(s):  
Fojan Agahi ◽  
Cristina Juan ◽  
Guillermina Font ◽  
Ana Juan-García
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Disruption

scholarly journals The Human Transcriptome During Nontyphoid Salmonella and HIV Coinfection Reveals Attenuated NFκB-Mediated Inflammation and Persistent Cell Cycle Disruption

2011 ◽  
Vol 204 (8) ◽  
pp. 1237-1245 ◽  
Author(s):  
Fernanda Schreiber ◽  
David J. Lynn ◽  
Angela Houston ◽  
Joanna Peters ◽  
Gershom Mwafulirwa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Human Transcriptome ◽  
Hiv Coinfection ◽  
Cell Cycle Disruption ◽  
Persistent Cell

Targeted Modulation of FAK/PI3K/PDK1/AKT and FAK/p53 Pathways by Cucurbitacin B for the Antiproliferation Effect Against Human Cholangiocarcinoma Cells

2020 ◽  
Vol 48 (06) ◽  
pp. 1475-1489
Author(s):  
Sirinapha Klungsaeng ◽  
Veerapol Kukongviriyapan ◽  
Auemduan Prawan ◽  
Sarinya Kongpetch ◽  
Laddawan Senggunprai
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Cucurbitacin B ◽  
M Phase ◽  
Cell Cycle Disruption

Inadequate responses to traditional chemotherapeutic agents in cholangiocarcinoma (CCA) emphasize a requirement for new effective compounds for the treatment of this malignancy. This study aimed to investigate the antiproliferative property of cucurbitacin B on KKU-100 CCA cells. The determination of underlying molecular mechanisms was also carried out. The results revealed that cucurbitacin B suppressed growth and replicative ability to form colonies of CCA cells, suggesting the antiproliferative effect of this compound against the cells. Flow cytometry analysis demonstrated that the interfering effect of cucurbitacin B on the CCA cell cycle at the G2/M phase was accountable for its antiproliferation property. Accompanied with cell cycle disruption, cucurbitacin B altered the expression of proteins involved in the G2/M phase transition including downregulation of cyclin A, cyclin D1, and cdc25A, and upregulation of p21. Additional molecular studies demonstrated that cucurbitacin B suppressed the activation of focal adhesion kinase (FAK) which consequently resulted in inhibition of its kinase-dependent and kinase-independent downstream targets contributing to the regulation of cell proliferation including PI3K/PDK1/AKT and p53 proteins. In this study, the transient knockdown of FAK using siRNA was employed to ascertain the role of FAK in CCA cell proliferation. Finally, the effect of cucurbitacin B on upstream receptor tyrosine kinases regulating FAK activation was elucidated. The results showed that the inhibitory effect of cucurbitacin B on FAK activation in CCA cells is mediated via interference of EGFR and HER2 expression. Collectively, cucurbitacin B might be a promising drug for CCA treatment by targeting FAK protein.

Simultaneous Inhibition of Mcl-1 and XIAP To Induce Apoptosis in AML Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1520-1520
Author(s):  
Bing Z. Carter ◽  
Duncan Mak ◽  
Wendy Schober ◽  
Erich Koller ◽  
Nicholas M. Dean ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Signaling Pathway ◽  
Antisense Oligonucleotide ◽  
Annexin V ◽  
Mapk Signaling ◽  
Caspase Inhibitor ◽  
Caspase Activation ◽  
Simultaneous Inhibition ◽  
Apoptotic Cascade

Abstract The apoptotic cascade is regulated by both upstream Bcl-2 and the distal IAP family proteins. Mcl-1, a member of antiapoptotic Bcl-2 family proteins is highly expressed in various cancer cells. It was reported that its expression is elevated at the time of leukemic relapse (Blood1998;19:991–1000). XIAP, the most potent cellular caspase inhibitor, inhibits both the initiator caspase-9 and the effector caspase-3 and suppresses apoptosis. Our previous study showed that decrease of XIAP by its antisense oligonucleotide enhances Ara-C-induced apoptosis (Leukemia2003;17:2081–2089). In this study, we investigated the regulation of Mcl-1 expression, its potential as a therapeutic target, and apoptosis induction by simultaneous inhibition of Mcl-1 and XIAP in AML cells. We found that like survivin, Mcl-1 protein level is decreased by MEK inhibition in HL-60 and OCI-AML2 cells suggesting that Mcl-1 expression is regulated through the MAPK signaling pathway. However, in contrast to survivin levels, no significant differences in Mcl-1 expression in G0/G1, S, and G2M cells were observed in FACS-sorted HL-60 cells. Downregulation of Mcl-1 by its antisense oligonucleotide (Mcl-1-AS, 20408, ISIS Pharmaceuticals) induced cell death accompanied by decrease in mitochondrial membrane potential (MMP), caspase activation and annexin V positivity in HL-60 cells, while control oligonucleotide was not toxic. By itself, MEK inhibitor primarily induced G1/G0 cell cycle block and no apoptosis. When combined with Mcl-1-AS, MEK inhibition further decreased Mcl-1 protein levels and significantly increased Mcl-1-AS induced cell death (from 25.8±1.3% to 40±3.8%, p=0.02). Inhibition of XIAP by its antisense oligonucleotide (XIAP-AS, 102369, ISIS Pharmaceuticals) did not induce significant loss of MMP at 24 hrs and slightly increased annexin V positive cells at 48 hrs (14.5%±2.9% dead cells vs. 6.2%±0.72% in XIAP-NS treated cells). However, when combined with Mcl-1 inhibition, significant increases in loss of MMP at 24 hrs and annexin V positive cells at 48 hrs (p=0.003), more than inhibition of each protein alone, was observed indicating that activating the upstream and downstream apoptotic cascade will amplify the caspase activation loop and more efficiently induce cell death. Our study suggests that Mcl-1 is regulated by the MAPK signaling pathway. Its expression is cell cycle independent. Mcl-1 is essential for HL-60 cell survival and simultaneously downregulation of the upstream anti-apoptotic protein Mcl-1 and the downstream caspase inhibitor XIAP significantly enhances leukemia cell apoptosis.

Nuclear failure, DNA damage, and cell cycle disruption after migration through small pores: a brief review

2019 ◽  
Vol 63 (5) ◽  
pp. 569-577
Author(s):  
Charlotte R. Pfeifer ◽  
Manasvita Vashisth ◽  
Yuntao Xia ◽  
Dennis E. Discher
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Local Density ◽  
Nuclear Lamina ◽  
Nuclear Deformation ◽  
Nuclear Factors ◽  
A Cell ◽  
Dense Tissue ◽  
Cell Cycle Disruption ◽  
Dependent Processes

Abstract In many contexts of development, regeneration, or disease such as cancer, a cell squeezes through a dense tissue or a basement membrane, constricting its nucleus. Here, we describe how the severity of nuclear deformation depends on a nucleus’ mechanical properties that are mostly determined by the density of chromatin and by the nuclear lamina. We explain how constriction-induced nuclear deformation affects nuclear contents by causing (i) local density changes in chromatin and (ii) rupture of the nuclear lamina and envelope. Both processes mislocalize diffusible nuclear factors including key DNA repair and regulatory proteins. Importantly, these effects of constricted migration are accompanied by excess DNA damage, marked by phosphorylated histone γH2AX in fixed cells. Rupture has a number of downstream consequences that include a delayed cell cycle—consistent with a damage checkpoint—and modulation of differentiation, both of which are expected to affect migration-dependent processes ranging from wound healing to tumorigenic invasion.

Cell Cycle Disruption in Wild Rodent Populations as an Endpoint in Detecting Exposure and Effect

2000 ◽  
Vol 64 (3) ◽  
pp. 448-454 ◽  
Author(s):  
J. K. Wickliffe ◽  
R. M. Pitts ◽  
S. Iverson ◽  
J. W. Bickham
Keyword(s):  
Cell Cycle ◽  
Wild Rodent ◽  
Cell Cycle Disruption ◽  
Rodent Populations

scholarly journals Impact of Cell Cycle Disruption on Impaired Hepatic Regeneration in Aged Livers with Ischemic Insult

2012 ◽  
Vol 173 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Atsushi Suzuki ◽  
Takanori Sakaguchi ◽  
Keisuke Inaba ◽  
Shohachi Suzuki ◽  
Hiroyuki Konno
Keyword(s):  
Cell Cycle ◽  
Hepatic Regeneration ◽  
Ischemic Insult ◽  
Cell Cycle Disruption

Aluminium-induced oxidative DNA damage recognition and cell-cycle disruption in different regions of rat brain

Toxicology ◽  
2009 ◽  
Vol 264 (3) ◽  
pp. 137-144 ◽  
Author(s):  
Vijay Kumar ◽  
Amanjit Bal ◽  
Kiran Dip Gill
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Rat Brain ◽  
Oxidative Dna Damage ◽  
Damage Recognition ◽  
Cell Cycle Disruption ◽  
Dna Damage Recognition
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