scholarly journals Ribophorin II is upregulated in myelodysplastic syndromes and prevents apoptosis and cell cycle progression

2020 ◽  
Vol 245 (12) ◽  
pp. 1009-1015
Author(s):  
Jinhai Ren ◽  
Ying Wang ◽  
Lihua Wang ◽  
Xiaoling Guo ◽  
Xiaonan Guo
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Myelodysplastic Syndromes ◽  
Cell Apoptosis ◽  
Dependent Manner ◽  
Hematopoietic Stem ◽  
Cycle Arrest ◽  
Ezh2 Expression ◽  
Enhancer Of Zeste

Myelodysplastic syndromes (MDSs) are a series of heterogeneous diseases affecting hematopoietic stem cells that result in hematopoiesis disturbance and leukemic transformation. As an essential cell cycle regulator, ribophorin II (RPN2) has been extensively identified as a prospective predictor of prognosis in diverse malignant tumors. However, its effects on MDS are unclear. We observed increased mRNA expression RPN2 in samples from MDS patients, compared with samples from normal healthy controls. RPN2 overexpression promoted the proliferation of Ontario Cancer Institute OCI-acute myeloid leukemia 3 (OCI-AML3) cells, whereas RPN2 silencing clearly suppressed the proliferation of OCI-AML3 cells. Furthermore, RPN2 silencing caused G1/S cell cycle arrest and cell apoptosis. In addition, RPN2 overexpression led to a higher proportion of cells in the G2/M phase and reduced cell apoptosis. RPN2 overexpression downregulated enhancer of zeste homolog-2 (EZH2) expression, whereas RPN2 downregulation increased EZH2 expression in a dose-dependent manner. Co-immunoprecipitation showed an interaction between RPN2 and EZH2. Additionally, the administration of 3-deazaneplanocin A, an EZH2 inhibitor, reversed the function of RPN2 silencing in cell cycle arrest and apoptosis induction in OCI-AML3 cells. Hence, RPN2 is an essential regulator of cell proliferation. This study described the etiology of OCI-AML3 cell proliferation regulated by RPN2 and EZH2. Impact statement This study explored the role of ribophorin II (RPN2) in myelodysplastic syndromes (MDSs) cell proliferation and growth and revealed that RPN2 knockdown suppressed OCI-AML3 cell growth and proliferation and triggered cell cycle arrest and elicited apoptosis in OCI-AML3 cells. In addition, it shed light on the etiology of RPN2’s role in MDS cell proliferation that RPN2 can negatively impact enhancer of zeste homolog-2 (EZH2) expression, which in turn is able to modulate the cell cycle location and death in OCI-AML3 cells. Hence, RPN2 expression could be a latent predictor of prognosis in patients with MDS.

Celastrol inhibits the proliferation and induces apoptosis of colorectal cancer cells via downregulating NF-κB/COX-2 signaling pathways

2021 ◽  
Vol 21 ◽  
Author(s):  
Hua Zhang ◽  
Xiaojin Zhao ◽  
Fajun Shang ◽  
Huan Sun ◽  
Xu Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
The World ◽  
Cox 2

Background: Colorectal cancer (CRC) is the third-ranked malignant tumor in the world that contributes to the death of a major population of the world. Celastrol, a bioactive natural product isolated from the medicinal plant Tripterygium wilfordii Hook F, has been proved to be an effective anti-tumor inhibitor for multiple tumors. Objective: To reveal the therapeutic effect and underlying mechanisms of celastrol on CRC cells. Methods: CCK-8 and clonogenic assay were used to analyze the cell proliferation in CRC cells. Flow cytometry analysis was conducted to assess the cell cycle and cell apoptosis. Wound-healing and cell invasion assay were used to evaluate the migrating and invasion capability of CRC cells. The potential antitumor mechanism of celastrol was investigated by qPCR, western blot, and confocal immunofluorescence analyses. Results: Celastrol effectively inhibited CRC cell proliferation by activating caspase-dependent cell apoptosis and facilitating G1 cell cycle arrest in a dose-dependent manner, as well as cell migration and invasion by downregulating the MMP2 and MMP9. Mechanistic protein expression revealed that celastrol suppressed the expression of COX-2 by inhibiting the phosphorylation of NF-κB p65 and subsequently leading to cytoplasmic retention of p65 protein, thereby inhibiting its nuclear translocation and transcription activities. Conclusion: These findings indicate that celastrol is an effective inhibitor for CRC, regulating the NF-κB/COX-2 pathway, leading to the inhibition of cell proliferation characterized by cell cycle arrest and caspase-dependent apoptosis, providing a potential alternative therapeutic agent for CRC patients.

Effect of Metformin Intervention on Pancreatic β-Cell Apoptosis

2022 ◽  
Vol 12 (4) ◽  
pp. 873-877
Author(s):  
Dongqian Xie ◽  
Zhicheng Gao ◽  
Mei Liu ◽  
Defeng Wang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
High Glucose Condition ◽  
M Phase ◽  
Signaling Activation

Metformin is shown to have hypoglycemic effects. However, the relationship between metformin’s intervention in FFA-induced endoplasmic reticulum stress-mediated insulin resistance (IR) and insulin β-cell apoptosis under high-glucose condition remains unclear. Our study intends to assess their relationship. Human pancreatic β-cells were treated with metformin and cell proliferation and IR were detected by MTT assay along with detection of Wnt/β-catenin signaling by RT-PCR, cell cycle and apoptosis by flow cytometry. Metformin inhibited β cell proliferation which was mediated by FFA-induced endoplasmic reticulum stress in a time-dependent and dose-dependent manner as well as induced cell cycle arrest at G2/M phase. In addition, metformin inhibited β-catenin signaling activation and decreased the expression of c-myc, Dvl-2, survivin, Dvl-3, GSK-3β (p-ser9) and promoted GSK-3 (p-tyr216) and Axin-2 expression. In conclusion, metformin inhibits Wnt/β-catenin signaling and promotes FFA to induce endoplasmic reticulum stress, thereby mediating pancreatic β-cells behaviors.

Corydalis yanhusuo W.T. Wang Extract Inhibits MCF-7 Cell Proliferation by Inducing Cell Cycle G2/M Arrest

2011 ◽  
Vol 39 (03) ◽  
pp. 579-586 ◽  
Author(s):  
Zengtao Xu ◽  
Xiuping Chen ◽  
Qingwen Zhang ◽  
Lidian Chen ◽  
Yitao Wang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Chinese Herb ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Protein Expressions ◽  
Ros Formation ◽  
Cdc 2 ◽  
Mcf 7

Corydalis yanhusuo W.T. Wang (YHS) is a traditional Chinese herb widely prescribed for promoting blood circulation, reinforcing vital energy and alleviating pain. Our previous studies showed that an ethanol extract of YHS inhibits metastasis of breast cancer cells in vitro. In the present study, the anti-proliferative effect of the extract was determined by MTT assay and the LDH release was measured with a commercial kit. Intracellular reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) were monitored by CM- H2DCF-DA and JC-1 staining, respectively. Cell cycle was analyzed with propidium iodide (PI) staining by flow cytometry and protein expressions were measured by Western blotting. The YHS extract significantly inhibited MCF-7 cell proliferation in a dose-dependent manner. Significant increase of ROS formation and decrease of ΔΨm were observed. Furthermore, it induced MCF-7 cell cycle arrest at the G2/M phases. In addition, the p-cdc-2/cdc-2 protein expression ratio was increased while Rb and p21 protein expressions were decreased. The YHS extract inhibited MCF-7 proliferation by inducing G2/M cell cycle arrest, which might be mediated by inducing ROS formation, decreasing ΔΨm and regulating cell cycle related protein expressions.

scholarly journals The LINC00504/Mir-4739/KLK4 Axis Facilitates Cell Proliferation and Suppresses Cell Apoptosis Through Triggering The Wnt/Β-Catenin Pathway In Triple-Negative Breast Cancer Cells

2020 ◽  
Author(s):  
Di Wu ◽  
Hongyao Jia ◽  
Zhiru Zhang ◽  
Sijie Li
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Triple Negative Breast Cancer ◽  
Cell Apoptosis ◽  
Triple Negative ◽  
Luciferase Reporter ◽  
Cycle Arrest ◽  
Tnbc Cell

Abstract Background: Currently, long non-coding RNAs (lncRNAs) have been validated to exert critical influence on the malignant progression of triple-negative breast cancer (TNBC). LncRNA long intergenic non-protein coding RNA 504 (LINC00504) has been recently reported as a tumor facilitator in the cellular processes of several cancers. However, its function in TNBC remains unknown.Methods: CCK-8 and colony formation assays were used to detect the cell viability and proliferation in TNBC. Flow cytometry analysis was utilized to measure the cycle and apoptosis of TNBC cells. The levels of key proteins associated with cell apoptosis or the β-catenin pathway were detected through western blot analysis. The activity of the Wnt/β-catenin signaling pathway was measured by the TOP/FOP flash assay. ChIP assay was conducted to confirm the binding between LINC00504 and its transcription factor signal transducer and activator of transcription 3 (STAT3). RIP and luciferase reporter assays were used to detect and verify the interaction among LINC00504 and its downstream molecule.Results: LncRNA LINC00504 was upregulated in TNBC, and silenced LINC00504 suppressed cell proliferation and triggers cell cycle arrest at G0/G1 stage and cell apoptosis in TNBC cells. STAT3 can transcriptionally activate LINC00504 and LINC00504 served as a molecular sponge of microRNA (miR-4379). Kallikrein related peptidase 4 (KLK4) was the target gene of miR-4379 and activates the Wnt/β-catenin pathway. LINC00504 upregulated KLK4 via competitively binding with miR-4379 to activate the Wnt/β-catenin pathway in TNBC. The suppression on TNBC cell proliferation and the promotion on TNBC cell cycle arrest and apoptosis under LINC00504 knockdown were rescued by miR-4379 depletion or KLK4 overexpression.Conclusions: The LINC00504/miR-4379/KLK4 axis promotes cell growth and cell cycle progression as well as suppresses cell apoptosis through activating the Wnt/β-catenin pathway.

scholarly journals Crocin Exhibits Antitumor Effects on Human Leukemia HL-60 Cells In Vitro and In Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yan Sun ◽  
Hui-Juan Xu ◽  
Yan-Xia Zhao ◽  
Ling-Zhen Wang ◽  
Li-Rong Sun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Nude Mice ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Tumor Weight ◽  
Cycle Arrest

Crocin is a carotenoid of the saffron extract that exhibits antitumor activity against many human tumors. However, the effects of crocin on HL-60 cells in vivo have not been evaluated. This study aimed to examine the effects of crocin on HL-60 cells in vitro and in vivo and investigate the underlying mechanisms. HL-60 cells were treated by crocin, and cell proliferation, apoptosis, and cell cycle profiles were examined by MTT assay, AO/EB staining, and flow cytometry, respectively. Furthermore, HL-60 cells were xenografted into nude mice and treated by crocin, the tumor weight and size were calculated, and the expression of Bcl-2 and Bax in xenografts was detected by immunohistochemical staining. The results showed that crocin (0.625–5 mg/mL) inhibited HL-60 cell proliferation and induced apoptosis and cell cycle arrest at G0/G1 phase, in a concentration and time-dependent manner. In addition, crocin (6.25, 25 mg/kg) inhibited the tumor weight and size of HL-60 xenografts in nude mice, inhibited Bcl-2 expression, and increased Bax expression in xenografts. In summary, crocin inhibits the proliferation and tumorigenicity of HL-60 cells, which may be mediated by the induction of apoptosis and cell cycle arrest and the regulation of Bcl-2 and Bax expression.

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