scholarly journals P8‐164: Paclitaxel inhibits EGFR‐mutated PC9 cell proliferation via the induction of necroptosis and G1 phase arrest

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 352-352
Keyword(s):  
Cell Proliferation ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Egfr Mutated

scholarly journals Cell Proliferation and Motility Are Inhibited by G1 Phase Arrest in 15-kDa Selenoprotein-Deficient Chang Liver Cells

2015 ◽  
Vol 38 (5) ◽  
pp. 457-465 ◽  
Author(s):  
Jeyoung Bang ◽  
Jang Hoe Huh ◽  
Ji-Woon Na ◽  
Qiao Lu ◽  
Bradley A. Carlson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cells ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Chang Liver

scholarly journals ESRP1 Induces Cervical Cancer Cell G1-Phase Arrest Via Regulating Cyclin A2 mRNA Stability

2019 ◽  
Vol 20 (15) ◽  
pp. 3705 ◽  
Author(s):  
Zhi-Hong Chen ◽  
Ya-Jie Jing ◽  
Jian-Bo Yu ◽  
Zai-Shu Jin ◽  
Zhu Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Cyclin A2 ◽  
The Stability

Accumulating evidence indicates that epithelial splicing regulatory protein 1 (ESRP1) can inhibit the epithelial-to-mesenchymal transition (EMT), thus playing a central role in regulating the metastatic progression of tumors. However, it is still not clear whether ESRP1 directly influences the cell cycle, or what the possible underlying molecular mechanisms are. In this study, we showed that ESRP1 protein levels were significantly correlated with the Ki-67 proliferative index (r = −0.521; p < 0.01), and that ESRP1 overexpression can significantly inhibit cervical carcinoma cell proliferation and induced G1-phase arrest by downregulating cyclin A2 expression. Importantly, ESRP1 can bind to GGUGGU sequence in the 3′UTR of the cyclin A2 mRNA, and ESRP1 overexpression significantly decreases the stability of the cyclin A2 mRNA. In addition, our experimental results confirm that ESRP1 overexpression results in enhanced CDC20 expression, which is known to be responsible for cyclin A2 degradation. This study provides the first evidence that ESRP1 overexpression induces G1-phase cell cycle arrest via reducing the stability of the cyclin A2 mRNA, and inhibits cervical carcinoma cell proliferation. The findings suggest that the ESRP1/cyclin A2 regulatory axis may be essential as a regulator of cell proliferation, and may thus represent an attractive target for cervical cancer prevention and treatment.

scholarly journals BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis

2020 ◽  
Vol 11 ◽  
pp. 204062072093268
Author(s):  
Guang Li ◽  
Yan-Hua Zheng ◽  
Li Xu ◽  
Juan Feng ◽  
Hai-Long Tang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Tumor Model ◽  
G1 Phase ◽  
Bortezomib Treatment ◽  
Phase Arrest ◽  
G1 Phase Arrest

Background: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. Methods: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. Results: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. Conclusion: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM.

scholarly journals Caffeine Inhibits Cell Proliferation by G0/G1 Phase Arrest in JB6 Cells

2004 ◽  
Vol 64 (9) ◽  
pp. 3344-3349 ◽  
Author(s):  
Takashi Hashimoto ◽  
Zhiwei He ◽  
Wei-Ya Ma ◽  
Patricia C. Schmid ◽  
Ann M. Bode ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Jb6 Cells

ECPIRM, a Potential Therapeutic Agent for Cutaneous T-Cell Lymphoma, Inhibits Cell Proliferation and Promotes Apoptosis via a JAK/STAT Pathway

2018 ◽  
Vol 18 (3) ◽  
pp. 401-411 ◽  
Author(s):  
Hua Yang ◽  
Pengcheng Ma ◽  
Yuping Cao ◽  
Mengli Zhang ◽  
Lingjun Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
T Cell ◽  
Biological Activities ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Stat Signaling ◽  
Induced Apoptosis ◽  
Stat Pathway

Background: Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells. Objective: The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM. Methods: The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis. Results: ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling. Conclusion: ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.

scholarly journals Ubiquitin Ligase Cbl-b Is Involved in Icotinib (BPI-2009H)-Induced Apoptosis and G1 Phase Arrest ofEGFRMutation-Positive Non-Small-Cell Lung Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaodong Mu ◽  
Ye Zhang ◽  
Xiujuan Qu ◽  
Kezuo Hou ◽  
Jian Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Ubiquitin Ligase ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
G1 Phase ◽  
Small Cell Lung ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Egfr Mutated

Epidermal growth factor receptor (EGFR) is one of the most promising targets for non-small-cell lung cancer (NSCLC). Icotinib, a highly selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has shown promising clinical efficacy and safety in patients with NSCLC. The exact molecular mechanism of icotinib remains unclear. In this study, we first investigated the antiproliferative effect of icotinib on NSCLC cells. Icotinib significantly inhibited proliferation of the EGFR-mutated lung cancer HCC827 cells. The IC50values at 48 and 72 h were 0.67 and 0.07 μM, respectively. Flow cytometric analysis showed that icotinib caused the G1 phase arrest and increased the rate of apoptosis in HCC827 cells. The levels of cyclin D1 and cyclin A2 were decreased. The apoptotic process was associated with activation of caspase-3, -8, and poly(ADP-ribose) polymerase (PARP). Further study revealed that icotinib inhibited phosphorylation of EGFR, Akt, and extracellular signal-regulated kinase. In addition, icotinib upregulated ubiquitin ligase Cbl-b expression. These observations suggest that icotinib-induced upregulation of Cbl-b is responsible, at least in part, for the antitumor effect of icotinib via the inhibition of phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase pathways in EGFR-mutated NSCLC cells.

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