scholarly journals Diosmetin Inhibits Cell Proliferation, Induces Cell Apoptosis and Cell Cycle Arrest in Liver Cancer

2020 ◽  
Vol Volume 12 ◽  
pp. 3537-3546 ◽  
Author(s):  
Aiqing Ma ◽  
Rui Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Liver Cancer ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Cycle Arrest

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.

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.

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 BAI1 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer via Modulating p73 Transactivation

2020 ◽  
Author(s):  
Xia yang ◽  
Ping Wei ◽  
Ruohong Shui
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Triple Negative Breast Cancer ◽  
Cell Apoptosis ◽  
Transcriptional Activity ◽  
Triple Negative ◽  
Cycle Arrest ◽  
Underlying Mechanisms

Abstract Background: Brain-specific angiogenesis inhibitor 1 (BAI1) which belongs to putative G-protein-coupled receptors (GPCRs), has been found down-expressed in various cancers and involved in cancer pathogenesis. However, the role and underlying mechanisms of BAI1 in triple negative breast cancer (TNBC) are still unclear. Methods: The expression levels of BAI1 in TNBC samples and cell lines were examined by immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting (WB). The functional effects of BAI1 on biological behaviors of TNBC cells were detected using plasmid and siRNA for BAI1 overexpression and knockdown, and the underlying mechanisms were investigated by Immunoprecipitation (IP), immunofluorescence (IF) and luciferase reporter assay. Results: BAI1 was downregulated in TNBC tissues and was significantly associated with poor disease-free survival. Functional experiments indicated that BAI1 inhibited cell proliferation and induced cell apoptosis and cell cycle arrest. Additionally, BAI1 overexpressed cells were more sensitive to cisplatin. Mechanistically, BAI1 interacted with MDM2, thereby enhanced p73 transcriptional activity, then promoted p21and BAX mRNA and protein expression. Overexpression of p73 abolished the BAI1 knockdown induced cell proliferation and the G2 phase cell population of TNBC, the sensitivity to cisplatin also rescued by overregulating p73 in BAI1 knockdown TNBC cells. Conclusions: Our results indicate that BAI1 is a promising prognostic factor in TNBC, and the expression of BAI1 inhibits cell proliferation and induces cell apoptosis and cell cycle arrest; Meanwhile, BAI1 increases the sensitivity of TNBC to cisplatin. For the underlying mechanism, BAI1 specifically binds to MDM2, and exerts its anti-tumor function by affecting the transcriptional activity of p73 protein, then inhibits the malignant progression of TNBC. The BAI1/MDM2/p73 axis may represent a potential target in the future research for TNBC.

scholarly journals PTENInhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/hTERTPathway in Lung Adenocarcinoma A549 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-Xiao Lu ◽  
Lan-Yu Cao ◽  
Xi Chen ◽  
Jian Xiao ◽  
Yong Zou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Akt Pathway ◽  
Wild Type ◽  
Cycle Arrest ◽  
Lung Adenocarcinoma A549

PTENplays an essential role in tumorigenesis and both its mutation and inactivation can influence proliferation, apoptosis, and cell cycle progression in tumor cells. However, the precise role ofPTENin lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutantPTENas well as A549 cells expressing a siRNA directed toward endogenousPTEN. Overexpression of wild-typePTENprofoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase proteinhTERT. In contrast, in cells expressing aPTENdirected siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, andhTERTprotein expression were observed. A549 cells transfected with aPTENmutant lacking phosphatase activity (PTEN-C124A) or an empty vector (null) did not show any effect. Furthermore, using the PI3K/AKT pathway blocker LY294002, we confirmed that the PI3K/AKT pathway was involved in mediating these effects ofPTEN. Taken together, we have demonstrated thatPTENdownregulates the PI3K/AKT/hTERTpathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma.

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