Eriocitrin, a dietary flavonoid suppressed cell proliferation, induced apoptosis through modulation of JAK2/STAT3 and JNK/p38 MAPKs signaling pathway in MCF‐7 cells

2021 ◽  
Author(s):  
Chengliang Yuan ◽  
Guoping Chen ◽  
Chengbao Jing ◽  
Mengxue Liu ◽  
Bo Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Dietary Flavonoid ◽  
Induced Apoptosis ◽  
Mcf 7 ◽  
P38 Mapks

scholarly journals miR-195 Regulates Proliferation and Apoptosis through Inhibiting the mTOR/p70s6k Signaling Pathway by Targeting HMGA2 in Esophageal Carcinoma Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yong Li ◽  
Dapeng Wu ◽  
Pei Wang ◽  
Xiaohui Li ◽  
Gongning Shi
Keyword(s):  
Cell Proliferation ◽  
Esophageal Carcinoma ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Ki 67 ◽  
Proliferation And Apoptosis ◽  
Ec Cells ◽  
Induced Apoptosis

miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC). The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC. The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown. In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated. Dual-luciferase reporter assay demonstrated that HMGA2 is a target of miR-195. MTT assay and flow cytometry revealed that miR-195 overexpression inhibited cell proliferation and induced apoptosis by targeting HMGA2. We also found that HMGA2 restored the inhibitory effect of miR-195 on phosphorylation of mTOR and p70S6K. Furthermore, rapamycin, a specific inhibitor of the mTOR/p70S6K signaling pathway, decreased the levels of Ki-67 and Bcl-2/Bax ratio, inhibited cell proliferation, and promoted apoptosis in EC cells. In conclusion, upregulation of miR-195 significantly suppressed cell growth and induced apoptosis of EC cells via suppressing the mTOR/p70s6k signaling pathway by targeting HMGA2.

scholarly journals MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC

2020 ◽  
Vol 28 (2) ◽  
pp. 147-159 ◽  
Author(s):  
ZiJun Liao ◽  
Qi Zheng ◽  
Ting Wei ◽  
YanBing Zhang ◽  
JieQun Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Exogenous Expression ◽  
Induced Apoptosis

MicroRNAs (miRNAs) play crucial roles in tumorigenesis and tumor progression. miR-561 has been reported to be downregulated in gastric cancer and affects cancer cell proliferation and metastasis. However, the role and underlying molecular mechanism of miR-561 in human non-small cell lung cancer (NSCLC) remain unknown and need to be further elucidated. In this study, we discovered that miR-561 expression was downregulated in human NSCLC tissues and cell lines. The overexpression of miR-561 inhibited NSCLC cell proliferation and cell cycle G1/S transition and induced apoptosis. The inhibition of miR-561 facilitated cell proliferation and G1/S transition and suppressed apoptosis. miR-561 expression was inversely correlated with P-REX2a expression in NSCLC tissues. P-REX2a was confirmed to be a direct target of miR-561 using a luciferase reporter assay. The overexpression of miR-561 decreased P-REX2a expression, and the suppression of miR-561 increased P-REX2a expression. Particularly, P-REX2a silencing recapitulated the cellular and molecular effects observed upon miR-561 overexpression, and P-REX2a overexpression counteracted the effects of miR-561 overexpression on NSCLC cells. Moreover, both exogenous expression of miR-561 and silencing of P-REX2a resulted in suppression of the PTEN/AKT signaling pathway. Our study demonstrates that miR-561 inhibits NSCLC cell proliferation and G1/S transition and induces apoptosis through suppression of the PTEN/AKT signaling pathway by targeting P-REX2a. These findings indicate that miR-561 plays a significant role in NSCLC progression and serves as a potential therapeutic target for NSCLC.

scholarly journals miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway

2018 ◽  
Vol 26 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Xiaowen Chen ◽  
Jianli Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
And Migration ◽  
Mcf 7

This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.

scholarly journals Radiation-Triggered NF-κB Activation is Responsible for the Angiogenic Signaling Pathway and Neovascularization for Breast Cancer Cell Proliferation and Growth

2012 ◽  
Vol 6 ◽  
pp. BCBCR.S9592 ◽  
Author(s):  
Hui Yu ◽  
Sumathy Mohan ◽  
Mohan Natarajan
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Radiation Exposure ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Mcf 7

Tumors require blood supply to survive, grow, and metastasize. This involves the process of angiogenesis signaling for new blood vessel growth into a growing tumor mass. Understanding the mechanism of the angiogenic signaling pathway and neovascularization for breast cancer cell proliferation and growth would help to develop molecular interventions and achieve disease free survival. Our hypothesis is that the surviving cancer cell(s) after radiotherapy can initiate angiogenic signaling pathway in the neighboring endothelial cells resulting in neovascularization for breast cancer cell growth. The angiogenic signaling pathway is initiated by angiogenic factors, VEGF and FGF-2, through activation of a transcriptional regulator NF-κB, which in turn is triggered by therapeutic doses of radiation exposure Human breast adenocarcinoma cells (MCF-7 cells) were exposed to Cesium-137 (137Cs) γ rays to a total dose of 2 Gy at a dose rate of 1.03 Gy/min. The results of mobility shift assay showed that radiation at clinical doses (2 Gy) could induce NF-κB DNA-binding activity. Then, we examined the communication of angiogenic signals from irradiated MCF-7 cells to vascular endothelial cells. At the protein level, the western blot showed induction of angiogenic factors VEGF and FGF-2 in MCF-7 cells irradiated with 2 Gy. Inhibition of NF-κB activation attenuated VEGF and FGF-2 levels. These factors are secreted into the medium. The levels of VEGF and FGF-2 in the extra cellular medium were both increased, after 2 Gy exposures. We also observed corresponding expression of VEGFR2 and FGFR1 in non-irradiated endothelial cells that were co-cultured with irradiated MCF-7 cells. In support of this, in vitro tube formation assays provided evidence that irradiated MCF-7 cells transmit signals to potentiate cultured non-irradiated endothelial cells to form tube networks, which is the hallmark of neovascularization. Inhibition of NF-κB activation attenuated irradiated MCF-7-induced tube network formation. The data provide evidence that the radiation exposure is responsible for tumor growth and maintenance by inducing an angiogenic signaling pathway through activation of NF-κB.

scholarly journals Molecular Mechanism Analysis the Apoptosis of Leukemia Cells Induced By CRM1 Selective Inhibitor KPT-330

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5901-5901 ◽  
Author(s):  
Jun Lu ◽  
Shaoyan Hu ◽  
Weiwei DU ◽  
Jian Pan ◽  
Junli Ren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Differentially Expressed Genes ◽  
Cell Apoptosis ◽  
Leukemia Cells ◽  
Glutathione Metabolism ◽  
Toll Like Receptor ◽  
Receptor Signaling Pathway ◽  
Induced Apoptosis

Abstract Objective: To investigate the effect and mechanisms of KPT-330 on cell apoptosis of human leukemia cells. Methods: CCK-8 assay was used to quantify the growth inhibition of cells after exposure to KPT-330 for 24 hours. Fluorescence microscope was used to observe the morphological change of leukemia cell when treated with KPT330 for 24 hours. Annexin V/propidium iodide staining followed by flow cytometric analysis was used to detect apoptosis of leukemia cells. Then Western blot was used to detect the expression level of CRM1 and the activation of apoptosis related protein Caspase-9、Caspase-3 and PARP level. LncRNA microarray was used to analyze the differentially expressed genes from the cluster analyses. Results: The inhibition of cell proliferation of leukemia cells was in a dose-dependent manner and KPT-330 treatment induced expression of CRM1 down-regulated .Abnormal cells were observed under fluorescence microscopy. Cell apoptosis, cell cycle and activation of apoptosis markers demonstrates that KPT-330 induced apoptosis in leukemia cells. LncRNA microarray analysis showed differently expressed mRNAs and lncRNAs in KPT-330 treated HL-60 cells compared with control group. Molecular function analysis showed that KPT-330 induced apoptosis in leukemia cells partially related with Glutathione metabolism and Toll-like receptor signaling pathway. Conclusion: In this study, KPT-330 treatment resulted in inhibition of cell proliferation and induction of apoptosis in leukemia cells. LncRNA microarray analysis showed differentially expressed genes and lncRNAs in KPT-330 treated HL-60 cells and we demonstrated that KPT-330 induced apoptosis in leukemia cells partially related with Glutathione metabolism and Toll-like receptor signaling pathway. These results may provide new clue about molecular mechanism of KPT-330 induced apoptosis; however, underlying details will be required to determine further. Taken together, our findings suggest that for the first time that KPT-330 may act as new candidate's drug for leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nuclear receptor 4A1 as a drug target for breast cancer chemotherapy

2015 ◽  
Vol 22 (5) ◽  
pp. 831-840 ◽  
Author(s):  
Erik Hedrick ◽  
Syng-Ook Lee ◽  
Ravi Doddapaneni ◽  
Mandip Singh ◽  
Stephen Safe
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Nuclear Receptor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Induced Apoptosis ◽  
Mcf 7

The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in mammary tumors and breast cancer cell lines. The functional activity of this receptor was investigated by RNA interference with oligonucleotides targeted to NR4A1 (siNR4A1) and by treatment with NR4A1 antagonists. Breast cancer cells were treated with NR4A1 antagonists or transfected with siNR4A. Effects on cell proliferation and apoptosis as well as specific genes associated with these responses were investigated in MCF-7, SKBR3, and MDA-MB-231 cells, and in athymic nude mice bearing MDA-MB-231 cells as xenografts. Transfection of MCF-7, MDA-MB-231, and SKBR3 breast cancer cells with siNR4A1 decreased cell proliferation and induced apoptosis in these cell lines. Transfection of breast cancer cells with siNR4A1 also decreased expression of Sp-regulated genes includingsurvivin,bcl-2, and epidermal growth factor receptor, inhibited mTOR signaling in MCF-7 cells that express WT p53, and activated oxidative and endoplasmic reticulum stress through downregulation of thioredoxin domain-containing 5 and isocitrate dehydrogenase 1. 1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes (C-DIMs) are NR4A1 ligands that act as NR4A1 antagonists. Treatment with selected analogs also inhibited breast cancer cell and tumor growth and induced apoptosis. The effects of C-DIM/NR4A1 antagonists were comparable to those observed after NR4A1 knockdown. Results with siNR4A1 or C-DIMs/NR4A1 antagonists in breast cancer cells and tumors were similar to those previously reported in pancreatic, lung, and colon cancer cells. They demonstrate the potential clinical applications of NR4A1 antagonists in patients with tumors that overexpress this receptor.

scholarly journals Dibenzofuran, 4-Chromanone, Acetophenone, and Dithiecine Derivatives: Cytotoxic Constituents from Eupatorium fortunei

2021 ◽  
Vol 22 (14) ◽  
pp. 7448
Author(s):  
Chun-Hao Chang ◽  
Semon Wu ◽  
Kai-Cheng Hsu ◽  
Wei-Jan Huang ◽  
Jih-Jung Chen
Keyword(s):  
Cell Proliferation ◽  
Aerial Part ◽  
Caspase 3 ◽  
Colony Formation Assay ◽  
Western Blot Test ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
New Compounds ◽  
Potent Inhibitory Activity ◽  
Mcf 7

Five new compounds, eupatodibenzofuran A (1), eupatodibenzofuran B (2), 6-acetyl-8-methoxy-2,2-dimethylchroman-4-one (3), eupatofortunone (4), and eupatodithiecine (5), have been isolated from the aerial part of Eupatorium fortunei, together with 11 known compounds (6‒16). Compounds 1 and 2 featured a new carbon skeleton with an unprecedented 1-(9-(4-methylphenyl)-6-methyldibe nzo[b,d]furan-2-yl)ethenone. Among the isolates, compound 1 exhibited potent inhibitory activity with IC50 values of 5.95 ± 0.89 and 5.55 ± 0.23 μM, respectively, against A549 and MCF-7 cells. The colony-formation assay demonstrated that compound 1 (5 μM) obviously decreased A549 and MCF-7 cell proliferation, and Western blot test confirmed that compound 1 markedly induced apoptosis of A549 and MCF-7 cells through mitochondrial- and caspase-3-dependent pathways.

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