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HES1 Inhibitor

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https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#1
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27880939/inhibition-of-the-transcriptional-repressor-complex-bcl-6-bcor-induces-endothelial-sprouting-but-does-not-promote-tumor-growth
#2
Elisabeth Buchberger, Dietmar Payrhuber, Miriam El Harchi, Branislav Zagrapan, Katharina Scheuba, Anna Zommer, Edina Bugyik, Balazs Dome, Julia Barbara Kral, Waltraud Cornelia Schrottmaier, Gernot Schabbauer, Peter Petzelbauer, Marion Gröger, Martin Bilban, Christine Brostjan
The oncogenic potential of the transcriptional repressor Bcl-6 (B-cell lymphoma 6) was originally discovered in non-Hodgkin patients and the soluble Bcl-6 inhibitor 79-6 was developed to treat diffuse large B-cell lymphomas with aberrant Bcl-6 expression. Since we found Bcl-6 and its co-repressor BCoR (Bcl-6 interacting co-repressor) to be regulated in human microvascular endothelium by colorectal cancer cells, we investigated their function in sprouting angiogenesis which is central to tumor growth. Based on Bcl-6/BCoR gene silencing we found that the transcriptional repressor complex in fact constitutes an endogenous inhibitor of vascular sprouting by supporting the stalk cell phenotype: control of Notch target genes (HES1, HEY1, DLL4) and cell cycle regulators (cyclin A and B1)...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27861873/notch-signaling-pathway-regulates-angiogenesis-via-endothelial-cell-in-3d-co-culture-model
#3
Dan Zhao, Changyue Xue, Shiyu Lin, Sirong Shi, Qianshun Li, Mengting Liu, Xiaoxiao Cai, Yunfeng Lin
This study aimed to investigate the role of Notch signaling pathway for angiogenesis in a three-dimensional (3D) collagen gel model with co-culture of adipose-derived stromal cells (ASCs) and endothelial cells (ECs). A 3D collagen gel model was established in vitro by implanting both ASCs from green fluorescent protein-labeled mouse and ECs from red fluorescent protein-labeled mouse, and the phenomena of angiogenesis with Notch signaling inducer Jagged1, inhibitor DAPT and PBS, respectively were observed by confocal laser scanning microscopy...
November 10, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27852366/-effects-and-mechanisms-of-notch-signaling-pathway-on-immune-imbalance-in-chronic-obstructive-pulmonary-disease
#4
X N Yang, X J Liu, L T Zhao, X L Zeng, H R Bao
Objective: To explore the role of Notch signaling pathway on immune imbalance in chronic obstructive pulmonary disease (COPD). Methods: Thirty BALB/c mice were randomly assigned into the healthy control group, COPD group, and COPD Gamma secretase inhibitors (GSI) group. Cigarette smoke exposure was used to establish the COPD model. T cells were enriched by filtering through nylon wool columns. The proportion of spleen-derived T-lymphocyte subsets was detected by flow cytometry. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to detect the expression of splenic T cells' Notch1 and its downstream Hes1 mRNA and protein respectively...
November 12, 2016: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27821050/stringent-comparative-sequence-analysis-reveals-sox10-as-a-putative-inhibitor-of-glial-cell-differentiation
#5
Chetna Gopinath, William D Law, José F Rodríguez-Molina, Arjun B Prasad, Lingyun Song, Gregory E Crawford, James C Mullikin, John Svaren, Anthony Antonellis
BACKGROUND: The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a context-dependent, pro-myelination transcription factor. As such, the identification of genes regulated by SOX10 will provide insight into Schwann cell biology and related diseases. While genome-wide studies have successfully revealed SOX10 target genes, these efforts mainly focused on myelinating stages of Schwann cell development...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27807176/hiv-tat-impairs-neurogenesis-through-functioning-as-a-notch-ligand-and-activation-of-notch-signaling-pathway
#6
Yan Fan, Xiang Gao, Jinhui Chen, Ying Liu, Johnny J He
: Alterations in adult neurogenesis have been noted in the brain of HIV-infected individuals and are likely linked to HIV-associated neurocognitive deficits, including those in learning and memory. But the underlying molecular mechanisms are not fully understood. In the study, we took advantage of doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) and determined the relationship between Tat expression and neurogenesis. Tat expression in astrocytes was associated with fewer neuron progenitor cells (NPCs), fewer immature neurons, and fewer mature neurons in the dentate gyrus of the hippocampus of the mouse brain...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27760204/fine-tuning-of-the-kaposi-s-sarcoma-associated-herpesvirus-life-cycle-in-neighboring-cells-through-the-rta-jag1-notch-pathway
#7
Shasha Li, Hao Hu, Zhiheng He, Deguang Liang, Rui Sun, Ke Lan
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27753144/melatonin-rescues-cardiac-thioredoxin-system-during-ischemia-reperfusion-injury-in-acute-hyperglycemic-state-by-restoring-notch1-hes1-akt-signaling-in-a-membrane-receptor-dependent-manner
#8
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
https://www.readbyqxmd.com/read/27677287/numb-notch-signaling-pathway-modulation-enhances-human-pancreatic-cancer-cell-radiosensitivity
#9
Yi-Liang Bi, Min Min, Wei Shen, Yan Liu
The present study aims to evaluate whether repression of the Numb/Notch signaling pathway affects the radiosensitivity of human pancreatic cancer cell lines. Different doses of X-rays (0, 2, 3, 4, and 5 Gy) were applied to the PANC-1, SW1990, and MIA PaCa-2 human pancreatic cancer cell lines, and the Numb/Notch pathway inhibitor DAPT was added at different doses (0, 1, 3, and 5 μmol/l). MTT assay, colony formation assay, flow cytometry, scratch assay, and Transwell experiments were performed, and qRT-PCR and Western blot were conducted for the detection of Numb expression...
September 27, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27661116/targeting-notch-signaling-as-a-novel-therapy-for-retinoblastoma
#10
Laura Asnaghi, Arushi Tripathy, Qian Yang, Harpreet Kaur, Allison Hanaford, Wayne Yu, Charles G Eberhart
Retinoblastoma is the most common intraocular malignancy of childhood. Notch plays a key role in retinal cells from which retinoblastomas arise, and we therefore studied the role of Notch signaling in promoting retinoblastoma proliferation. Moderate or strong nuclear expression of Hes1 was found in 10 of 11 human retinoblastoma samples analyzed immunohistochemically, supporting a role for Notch in retinoblastoma growth. Notch pathway components were present in WERI Rb1 and Y79 retinoblastoma lines, with Jag2 and DLL4 more highly expressed than other ligands, and Notch1 and Notch2 more abundant than Notch3...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27630117/protective-effect-of-melatonin-on-soluble-a%C3%AE-1-42-induced-memory-impairment-astrogliosis-and-synaptic-dysfunction-via-the-musashi1-notch1-hes1-signaling-pathway-in-the-rat-hippocampus
#11
Shuman Zhang, Pan Wang, Lili Ren, Chunli Hu, Jing Bi
BACKGROUND: Amyloid-beta (Aβ) plays a key role in Alzheimer's disease (AD) pathogenesis, and soluble Aβ oligomers are more cytotoxic than Aβ fibrils. Recent evidence suggests that Notch signaling is affected by AD and other brain diseases. Melatonin exerts beneficial effects on many aspects of AD and may protect against myocardial ischemia via Notch1 signaling regulation. Therefore, we hypothesized that the Notch1 signaling pathway is involved in the neuroprotective role of melatonin against soluble Aβ1-42...
2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27570480/gamma-secretase-inhibitor-prevents-proliferation-and-migration-of-ductus-arteriosus-smooth-muscle-cells-through-the-notch3-hes1-2-5-pathway
#12
Jiunn-Ren Wu, Jwu-Lai Yeh, Shu-Fen Liou, Zen-Kong Dai, Bin-Nan Wu, Jong-Hau Hsu
Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA closure. Notch signaling is an important mediator of vascular remodelling but its role in DA is unkonwn. We investigated the effects and underlying mechanisms of γ-secretase inhibitor DAPT, a Notch signaling inhibitor on angiotensin II (Ang II)-induced proliferation and migration of DASMCs. Proliferation and migration of DASMCs cultured from neonatal Wistar rats were induced by Ang II, with or without DAPT pre-treatment...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27476167/inhibition-on-numb-notch-signal-pathway-enhances-radiosensitivity-of-lung-cancer-cell-line-h358
#13
Shi-Gang Song, Hong-Yang Yu, Yan-Wei Ma, Feng Zhang, Xiang-Ying Xu
The objective of the study is to investigate the effects of the Numb/Notch signal pathway on the radiosensitivity of lung cancer cell line H358. MTT assay and colony forming assay were used to detect the effects of different doses of X-rays and MW167 on the in vitro proliferation of the lung cancer cell line H358. Flow cytometry was applied to evaluate the effects of X rays on the apoptosis of H358. Scratch assay and Transwell invasion assay were used to examine the effects of X-rays on the migration and invasion abilities of H358...
July 30, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27269414/use-of-hes1-gfp-reporter-mice-to-assess-activity-of-the-hes1-promoter-in-bone-cells-under-chronic-inflammation
#14
Hengwei Zhang, Wen Sun, Xing Li, Mengmeng Wang, Brendan F Boyce, Matthew J Hilton, Lianping Xing
Notch signaling plays a critical role in maintaining bone homeostasis partially by controlling the formation of osteoblasts from mesenchymal stem cells (MSCs). We reported that TNF activates Notch signaling in MSCs which inhibits osteoblast differentiation in TNF transgenic (TNF-Tg) mice, a mouse model of chronic inflammatory arthritis. In the current study, we used Hes1-GFP and Hes1-GFP/TNF-Tg mice to study the distribution and dynamic change of Notch active cells in normal and inflammatory bone loss and mechanisms mediating their enhanced proliferation...
September 2016: Bone
https://www.readbyqxmd.com/read/27220406/notch-signaling-represses-hypoxia-inducible-factor-1%C3%AE-induced-activation-of-wnt-%C3%AE-catenin-signaling-in-osteoblasts-under-cobalt-mimicked-hypoxia
#15
Chen-Tian Li, Jian-Xiu Liu, Bo Yu, Rui Liu, Chao Dong, Song-Jian Li
The modification of Wnt and Notch signaling pathways by hypoxia, and its association with osteoblast proliferation and apoptosis remain to be fully elucidated. To investigate Wnt-Notch crosstalk, and its role in hypoxia-induced osteoblast proliferation and apoptosis regulation, the present study investigated the effects of cobalt‑mimicked hypoxia on the mouse pre-osteoblast-like cell line, MC3T3‑E1, when the Notch signals were repressed using a γ‑secretase inhibitor DAPT. The data showed that the cobalt‑mimicked hypoxia suppressed cell proliferation under normal conditions, but increased cell proliferation under conditions of Notch repression, in a concentration‑dependent manner...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27206767/lfa-1-icam-1-ligation-in-human-t-cells-promotes-th1-polarization-through-a-gsk3%C3%AE-signaling-dependent-notch-pathway
#16
Navin K Verma, M H U Turabe Fazil, Seow Theng Ong, Madhavi Latha S Chalasani, Jian Hui Low, Amuthavalli Kottaiswamy, Praseetha P, Atish Kizhakeyil, Sunil Kumar, Aditya K Panda, Michael Freeley, Sinead M Smith, Bernhard O Boehm, Dermot Kelleher
In this study, we report that the integrin LFA-1 cross-linking with its ligand ICAM-1 in human PBMCs or CD4(+) T cells promotes Th1 polarization by upregulating IFN-γ secretion and T-bet expression. LFA-1 stimulation in PBMCs, CD4(+) T cells, or the T cell line HuT78 activates the Notch pathway by nuclear translocation of cleaved Notch1 intracellular domain (NICD) and upregulation of target molecules Hey1 and Hes1. Blocking LFA-1 by a neutralizing Ab or specific inhibition of Notch1 by a γ-secretase inhibitor substantially inhibits LFA-1/ICAM-1-mediated activation of Notch signaling...
July 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27183608/tgf-%C3%AE-signaling-in-dendritic-cells-governs-colonic-homeostasis-by-controlling-epithelial-differentiation-and-the-luminal-microbiota
#17
Sozaburo Ihara, Yoshihiro Hirata, Takako Serizawa, Nobumi Suzuki, Kosuke Sakitani, Hiroto Kinoshita, Yoku Hayakawa, Hayato Nakagawa, Hideaki Ijichi, Keisuke Tateishi, Kazuhiko Koike
Dendritic cells (DCs) mediate host immune responses to gut microbes and play critical roles in inflammatory bowel disease. In this study, we examined the role of TGF-β signaling in DCs in colonic homeostasis. CD11c-cre Tgfbr2(fl/fl) mice developed spontaneous colitis, and CD11c-cre Tgfbr2(fl/+) mice exhibited susceptibility to dextran sulfate sodium-induced colitis. Colitis in these mice was characterized by goblet cell depletion and dysbiosis caused by Enterobacteriaceae enrichment. Wild-type mice gavaged with Enterobacteriaceae from CD11c-cre Tgfbr2(fl/fl) mice feces showed severe colitis after dextran sulfate sodium treatment, whereas those treated with Notch inhibitor exhibited attenuated colonic injury with increased goblet cell numbers, thickened mucus layer, and fewer fecal Enterobacteriaceae Wild-type mice transplanted with CD11c-cre Tgfbr2(fl/fl) bone marrow developed colitis showing increased Jagged1 and Jagged2 in DCs, increased Hes1 levels in epithelium, and goblet cell depletion...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27176495/valproic-acid-exhibits-different-cell-growth-arrest-effect-in-three-hpv-positive-negative-cervical-cancer-cells-and-possibly-via-inducing-notch1-cleavage-and-e6-downregulation
#18
Shuyu Feng, Yue Yang, Jingyi Lv, Lichun Sun, Mingqiu Liu
We investigated the effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, and the mechanism of VPA-induced growth inhibition on three cervical cancer cell lines with different molecular and genetic background. We found that VPA induced proliferation suppression, cell apoptosis and cell cycle arrest in all tested cell lines, with an increase of Notch1 active form ICN1 as a tumor suppressor and its target gene HES1. Noteworthy, blocking of Notch signaling with DAPT resulted in growth inhibition in ICN1-overexpressing CaSki and HT-3 cells...
July 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27108536/notch1-inhibition-enhances-the-efficacy-of-conventional-chemotherapeutic-agents-by-targeting-head-neck-cancer-stem-cell
#19
Zhi-Li Zhao, Lu Zhang, Cong-Fa Huang, Si-Rui Ma, Lin-Lin Bu, Jian-Feng Liu, Guang-Tao Yu, Bing Liu, J Silvio Gutkind, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
Cancer stem cells (CSCs) are considered responsible for tumor initiation and chemoresistance. This study was aimed to investigate the possibility of targeting head neck squamous cell carcinoma (HNSCC) by NOTCH1 pathway inhibition and explore the synergistic effect of combining NOTCH inhibition with conventional chemotherapy. NOTCH1/HES1 elevation was found in human HNSCC, especially in tissue post chemotherapy and lymph node metastasis, which is correlated with CSCs markers. NOTCH1 inhibitor DAPT (GSI-IX) significantly reduces CSCs population and tumor self-renewal ability in vitro and in vivo...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27082308/microrna-101-inhibits-cell-proliferation-and-induces-apoptosis-by-targeting-eya1-in-breast-cancer
#20
Haitao Guan, Zhijun Dai, Yuguang Ma, Zhongwei Wang, Xiaoxu Liu, Xijing Wang
MicroRNAs (miRNAs or miRs) regulate gene expression by negatively modulating the stability or translational efficiency of their target genes by targeting the 3'-untranslated region (3'-UTR). Aberrant miRNA expression has been reported in various types of cancer; miRNAs can function as either oncogenes or tumor suppressor genes in cancer. In this study, we examined the expression level of miR‑101 in breast cancer tissues and cell lines by RT-qPCR, and found that miR‑101 expression was downregulated in breast cancer tissues and cell lines; indeed, in 6 of the 28 tissue samples, miR‑101 could not be detected...
June 2016: International Journal of Molecular Medicine
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