scholarly journals Dermal fibroblasts induce cell cycle arrest and block epithelial–mesenchymal transition to inhibit the early stage melanoma development

2016 ◽  
Vol 5 (7) ◽  
pp. 1566-1579 ◽  
Author(s):  
Linli Zhou ◽  
Kun Yang ◽  
R. Randall Wickett ◽  
Yuhang Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Dermal Fibroblasts ◽  
Induce Cell Cycle Arrest ◽  
Mesenchymal Transition ◽  
Cycle Arrest

scholarly journals Knockdown of SIRT1 Suppresses Bladder Cancer Cell Proliferation and Migration and Induces Cell Cycle Arrest and Antioxidant Response through FOXO3a-Mediated Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Qingxuan Hu ◽  
Gang Wang ◽  
Jianping Peng ◽  
Guofeng Qian ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Cycle Arrest ◽  
Metabolic Diseases ◽  
Epithelial Mesenchymal Transition ◽  
Cell Model ◽  
Antioxidant Response ◽  
Close Link ◽  
Mesenchymal Transition ◽  
Cycle Arrest

Bladder cancer (BCa) is one of the most common tumors, but its underlying mechanism has not been fully clarified. Our transcriptome analysis suggested a close link of Sirtuins, Peroxisome Proliferator-Activated Receptor (PPAR), cell cycle regulation, reactive oxygen species (ROS) metabolism, and Forkhead Box Class O (FOXO) signaling pathway in BCa. SIRT1 is a key member of Sirtuins, playing important roles in aging and energy metabolism, which has been reported to be involved in various metabolic diseases and tumors. We observed that SIRT1 was upregulated in BCa tissues at both mRNA and protein levels. By establishing a SIRT1-knockdown BCa cell model, our results suggested that proliferation and viability were suppressed. Moreover, migration rate was inhibited as well, possibly via reduction of epithelial-mesenchymal transition (EMT). In addition, cell cycle arrest was significantly induced, consisting with strongly decreased proteins involved (CDK2/4/6). Furthermore, ROS production was slightly reduced, accompanied by increasing of antioxidant enzymes and total/acetylated FOXO3a. Consistently with our Path-net analysis, we observed no significant alteration of apoptosis in the SIRT1-knockdown BCa cells. Taken together, our results suggested that SIRT1 deficiency in BCa cells could suppress cell viability by activating antioxidant response and inducing cell cycle arrest possibly via FOXO3a-related pathways.

scholarly journals Snai1-induced partial epithelial–mesenchymal transition orchestrates p53–p21-mediated G2/M arrest in the progression of renal fibrosis via NF-κB-mediated inflammation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruochen Qi ◽  
Jiyan Wang ◽  
Yamei Jiang ◽  
Yue Qiu ◽  
Ming Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Mesenchymal Transition ◽  
Cycle Arrest ◽  
Renal Fibrogenesis

AbstractRenal fibrosis is the common feature of all progressive kidney diseases and exerts great burden on public health worldwide. The maladaptive repair mechanism of tubular epithelial cells, an important mediator of renal fibrogenesis, manifests with partial epithelial–mesenchymal transition (EMT) and cell cycle arrest. The aim of this study is to investigate the possible correlation between partial EMT and cell cycle arrest, and elucidate the underlying mechanism. We examined human kidney allograft samples with interstitial fibrosis and three mice renal fibrosis models, unilateral ureter obstruction (UUO), ischemia–reperfusion injury, and Adriamycin nephropathy. The partial EMT process and p53–p21 axis were elevated in both human allograft with interstitial fibrosis, as well as three mice renal fibrosis models, and showed a time-dependent increase as fibrosis progressed in the UUO model. Snai1 controlled the partial EMT process, and led to parallel changes in renal fibrosis, G2/M arrest, and inflammation. p53–p21 axis arrested cell cycle at G2/M, and prompted partial EMT and fibrosis together with inflammation. NF-κB inhibitor Bay11-7082 disrupted the reciprocal loop between Snai1-induced partial EMT and p53–p21-mediated G2/M arrest. We demonstrated the reciprocal loop between partial EMT and G2/M arrest of TECs during renal fibrogenesis and revealed NF-κB-mediated inflammatory response as the underlying mechanism. This study suggests that targeting NF-κB might be a plausible therapeutic strategy to disrupt the reciprocal loop between partial EMT and G2/M arrest, therefore alleviating renal fibrosis.

scholarly journals Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial–Mesenchymal Transition

2021 ◽  
Vol 8 ◽  
Author(s):  
Yongmei Zhao ◽  
Kaikai Wang ◽  
Yuanlin Zheng ◽  
Xiaobao Zeng ◽  
Yi Chieh Lim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Cycle Arrest ◽  
Epithelial Mesenchymal Transition ◽  
Disease Recurrence ◽  
Cell Surface Glycoprotein ◽  
Efficient Treatment ◽  
Mesenchymal Transition ◽  
Cycle Arrest

Malignant cancer is a devastating disease often associated with a poor clinical prognosis. For decades, modern drug discoveries have attempted to identify potential modulators that can impede tumor growth. Cancer stem cells however are more resistant to therapeutic intervention, which often leads to treatment failure and subsequent disease recurrence. Here in this study, we have developed a specific multi-target drug delivery nanoparticle system against breast cancer stem cells (BCSCs). Therapeutic agents curcumin and salinomycin have complementary functions of limiting therapeutic resistance and eliciting cellular death, respectively. By conjugation of CD44 cell-surface glycoprotein with poly(lactic-co-glycolic acid) (PLGA) nanoparticles that are loaded with curcumin and salinomycin, we investigated the cellular uptake of BCSCs, drug release, and therapeutic efficacy against BCSCs. We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial–mesenchymal transition. This curcumin and salinomycin co-delivery system can be an efficient treatment approach to target malignant cancer without the repercussion of disease recurrence.

N6-Isopentenyladenosine and its Analogue N6-Benzyladenosine Induce Cell Cycle Arrest and Apoptosis in Bladder Carcinoma T24 Cells

2013 ◽  
Vol 13 (4) ◽  
pp. 672-678 ◽  
Author(s):  
Sara Castiglioni ◽  
Silvana Casati ◽  
Roberta Ottria ◽  
Pierangela Ciuffreda ◽  
Jeanette A.M. Maier
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Bladder Carcinoma ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
T24 Cells

scholarly journals Molecular disruption of DNA polymerase β for platinum sensitisation and synthetic lethality in epithelial ovarian cancers

Oncogene ◽  
2021 ◽  
Author(s):  
Reem Ali ◽  
Adel Alblihy ◽  
Islam M. Miligy ◽  
Muslim L. Alabdullah ◽  
Mansour Alsaleem ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Dna Polymerase ◽  
Synthetic Lethality ◽  
Ovarian Cancer Cells ◽  
Dna Polymerase Β ◽  
Mesenchymal Transition ◽  
Platinum Sensitivity ◽  
Cycle Arrest ◽  
Ovarian Cancers

AbstractTargeting PARP1 [Poly(ADP-Ribose) Polymerase 1] for synthetic lethality is a new strategy for BRCA germ-line mutated or platinum sensitive ovarian cancers. However, not all patients respond due to intrinsic or acquired resistance to PARP1 inhibitor. Development of alternative synthetic lethality approaches is a high priority. DNA polymerase β (Polβ), a critical player in base excision repair (BER), interacts with PARP1 during DNA repair. Here we show that polβ deficiency is a predictor of platinum sensitivity in human ovarian tumours. Polβ depletion not only increased platinum sensitivity but also reduced invasion, migration and impaired EMT (epithelial to mesenchymal transition) of ovarian cancer cells. Polβ small molecular inhibitors (Pamoic acid and NSC666719) were selectively toxic to BRCA2 deficient cells and associated with double-strand breaks (DSB) accumulation, cell cycle arrest and increased apoptosis. Interestingly, PARG [Poly(ADP-Ribose) Glycohydrolase] inhibitor (PDD00017273) [but not PARP1 inhibitor (Olaparib)] was synthetically lethal in polβ deficient cells. Selective toxicity to PDD00017273 was associated with poly (ADP-ribose) accumulation, reduced nicotinamide adenine dinucleotide (NAD+) level, DSB accumulation, cell cycle arrest and increased apoptosis. In human tumours, polβ-PARG co-expression adversely impacted survival in patients. Our data provide evidence that polβ targeting is a novel strategy and warrants further pharmaceutical development in epithelial ovarian cancers.

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