Cell Cycle Regulation of Hippocampal Progenitor Cells in Experimental Models of Depression and after Treatment with Fluoxetine

Changes in adult hippocampal cell proliferation and genesis have been largely implicated in depression and antidepressant action, though surprisingly, the underlying cell cycle mechanisms are largely undisclosed. Using both an in vivo unpredictable chronic mild stress (uCMS) rat model of depression and in vitro rat hippocampal-derived neurosphere culture approaches, we aimed to unravel the cell cycle mechanisms regulating hippocampal cell proliferation and genesis in depression and after antidepressant treatment. We show that the hippocampal dentate gyrus (hDG) of uCMS animals have less proliferating cells and a decreased proportion of cells in the G2/M phase, suggesting a G1 phase arrest; this is accompanied by decreased levels of cyclin D1, E, and A expression. Chronic fluoxetine treatment reversed the G1 phase arrest and promoted an up-regulation of cyclin E. In vitro, dexamethasone (DEX) decreased cell proliferation, whereas the administration of serotonin (5-HT) reversed it. DEX also induced a G1-phase arrest and decreased cyclin D1 and D2 expression levels while increasing p27. Additionally, 5-HT treatment could partly reverse the G1-phase arrest and restored cyclin D1 expression. We suggest that the anti-proliferative actions of chronic stress in the hDG result from a glucocorticoid-mediated G1-phase arrest in the progenitor cells that is partly mediated by decreased cyclin D1 expression which may be overcome by antidepressant treatment.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20153705 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3705 ◽

Cited By ~ 1

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.

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

Therapeutic Advances in Hematology ◽

10.1177/2040620720932686 ◽

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.

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6-Gingerol induces cell-cycle G1-phase arrest through AKT–GSK 3β–cyclin D1 pathway in renal-cell carcinoma

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-019-03999-9 ◽

2019 ◽

Vol 85 (2) ◽

pp. 379-390

Author(s):

Shan Xu ◽

Haibao Zhang ◽

Tianjie Liu ◽

Wenjie Yang ◽

Wei Lv ◽

...

Keyword(s):

Cell Cycle ◽

Renal Cell Carcinoma ◽

Cyclin D1 ◽

Renal Cell ◽

Colony Formation ◽

G1 Phase ◽

Phase Arrest ◽

G1 Phase Arrest ◽

Gsk 3Β

Abstract Purpose 6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary. Methods The effects of 6-gingerol on proliferation, colony formation, and cell cycle in RCC cells were detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and propidium iodide (PI) staining, respectively. Western blotting, an immunofluorescence assay, and immunohistochemical staining were performed to assess the expression of relevant proteins. A subcutaneous tumor model was set up to investigate the 6-gingerol effects on tumor growth in vivo, and the pharmacokinetics of 6-gingerol in mice were detected by LC/MS assays. Results 6-Gingerol treatment exerted time- and dose-dependent inhibition of the growth and colony formation of ACHN, 786-O, and 769-P cells, leading to a concomitant induction of cell-cycle G1-phase arrest and decrease in Ki-67 expression in the cell nucleus. Western-blotting results showed that 6-gingerol reduces phosphorylation of protein kinase B (AKT) Ser 473, cyclin-dependent kinases (CDK4), and cyclin D1 and, meanwhile, increases glycogen synthase kinase (GSK 3β) protein amount. Furthermore, the efficacy of 6-gingerol was demonstrated in an in vivo murine model of 786-O. Conclusion The above results indicate that 6-gingerol can induce cell-cycle arrest and cell-growth inhibition through the AKT–GSK 3β–cyclin D1 signaling pathway in vitro and in vivo, suggesting that 6-gingerol should be useful for renal-cell carcinoma treatment.

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Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

BMC Cancer ◽

10.1186/1471-2407-12-321 ◽

2012 ◽

Vol 12 (1) ◽

Cited By ~ 36

Author(s):

Fumihiko Uchida ◽

Katsuhiro Uzawa ◽

Atsushi Kasamatsu ◽

Hiroaki Takatori ◽

Yosuke Sakamoto ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Oral Cancer ◽

Cancer Progression ◽

G1 Phase ◽

Phase Arrest ◽

Cell Cycle Regulator ◽

G1 Phase Arrest

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Tubeimoside-1 induces oxidative stress-mediated apoptosis and G0/G1 phase arrest in human prostate carcinoma cells in vitro

Acta Pharmacologica Sinica ◽

10.1038/aps.2016.34 ◽

2016 ◽

Vol 37 (7) ◽

pp. 950-962 ◽

Cited By ~ 17

Author(s):

Jing-bo Yang ◽

Muhammad Khan ◽

Yang-yang He ◽

Min Yao ◽

Yong-ming Li ◽

...

Keyword(s):

Oxidative Stress ◽

Prostate Carcinoma ◽

Carcinoma Cells ◽

Human Prostate ◽

G1 Phase ◽

Phase Arrest ◽

G1 Phase Arrest ◽

Human Prostate Carcinoma

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

Molecules and Cells ◽

10.14348/molcells.2015.0007 ◽

2015 ◽

Vol 38 (5) ◽

pp. 457-465 ◽

Cited By ~ 15

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

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An in vitro attempt at precision toxicology reveals the involvement of DNA methylation alteration in ochratoxin A-induced G0/G1 phase arrest

Epigenetics ◽

10.1080/15592294.2019.1644878 ◽

2019 ◽

Vol 15 (1-2) ◽

pp. 199-214 ◽

Cited By ~ 4

Author(s):

Boyang Zhang ◽

Liye Zhu ◽

Yaqi Dai ◽

Hongyu Li ◽

Kunlun Huang ◽

...

Keyword(s):

Dna Methylation ◽

Ochratoxin A ◽

G1 Phase ◽

Methylation Alteration ◽

Phase Arrest ◽

G1 Phase Arrest

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Zona Occludens-2 Inhibits Cyclin D1 Expression and Cell Proliferation and Exhibits Changes in Localization along the Cell Cycle

Molecular Biology of the Cell ◽

10.1091/mbc.e08-03-0277 ◽

2009 ◽

Vol 20 (3) ◽

pp. 1102-1117 ◽

Cited By ~ 58

Author(s):

Rocio Tapia ◽

Miriam Huerta ◽

Socorro Islas ◽

Antonia Avila-Flores ◽

Esther Lopez-Bayghen ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cyclin D1 ◽

Target Gene ◽

Glycogen Synthase ◽

G1 Phase ◽

Junction Protein ◽

Cell Progression ◽

Zona Occludens ◽

Darby Canine Kidney

Here, we have studied the effect of the tight junction protein zona occludens (ZO)-2 on cyclin D1 (CD1) protein expression. CD1 is essential for cell progression through the G1 phase of the cell cycle. We have found that in cultures of synchronized Madin-Darby canine kidney cells, ZO-2 inhibits cell proliferation at G0/G1 and decreases CD1 protein level. These effects occur in response to a diminished CD1 translation and an augmented CD1 degradation at the proteosome triggered by ZO-2. ZO-2 overexpression decreases the amount of Glycogen synthase kinase-3β phosphorylated at Ser9 and represses β-catenin target gene expression. We have also explored the expression of ZO-2 through the cell cycle and demonstrate that ZO-2 enters the nucleus at the late G1 phase and leaves the nucleus when the cell is in mitosis. These results thus explain why in confluent quiescent epithelia ZO-2 is absent from the nucleus and localizes at the cellular borders, whereas in sparse proliferating cultures ZO-2 is conspicuously present at the nucleus.

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