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ICG-001

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https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#1
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28893318/icg-001-suppresses-growth-of-gastric-cancer-cells-and-reduces-chemoresistance-of-cancer-stem-cell-like-population
#2
Yi Liu, Hui Chen, Peiming Zheng, Yingxia Zheng, Qin Luo, Guohua Xie, Yanhui Ma, Lisong Shen
BACKGROUND: ICG-001, a small molecule, binds CREB-binding protein (CBP) to disrupt its interaction with β-catenin and inhibits CBP function as a co-activator of Wnt/β-catenin-mediated transcription. Given its ability to inhibit Wnt/β-catenin signaling pathway, ICG-001 has been used in some tumor types to exert its anticarcinogenic effect. Here, we examined ICG-001 and its potential role as a therapeutic in gastric cancer (GC). METHODS: The gastric cancer cell lines SGC-7901, MGC-803, BGC-823 and MKN-45 were used in vitro and in vivo...
September 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28837560/wnt-%C3%AE-catenin-signaling-pathway-inhibits-the-proliferation-and-apoptosis-of-u87-glioma-cells-via-different-mechanisms
#3
Liyang Gao, Bing Chen, Jinhong Li, Fan Yang, Xuecheng Cen, Zhuangbing Liao, Xiao'ao Long
The Wnt signaling pathway is necessary for the development of the central nervous system and is associated with tumorigenesis in various cancers. However, the mechanism of the Wnt signaling pathway in glioma cells has yet to be elucidated. Small-molecule Wnt modulators such as ICG-001 and AZD2858 were used to inhibit and stimulate the Wnt/β-catenin signaling pathway. Techniques including cell proliferation assay, colony formation assay, Matrigel cell invasion assay, cell cycle assay and Genechip microarray were used...
2017: PloS One
https://www.readbyqxmd.com/read/28810055/impact-of-mir-26b-on-cardiomyocyte-differentiation-in-p19-cells-through-regulating-canonical-non-canonical-wnt-signalling
#4
Duo Wang, Chang Liu, Yumei Wang, Wenjing Wang, Kang Wang, Xiujuan Wu, Zhigang Li, Cuimei Zhao, Li Li, Luying Peng
BACKGROUND AND OBJECTIVES: The control of cardiomyocyte differentiation is tightly linked to microRNAs (miRNAs), which have been emerging as important players in heart development. However, the regulation mechanisms mediated by miRNAs in early heart development remains speculative. Here, we evaluated the impact of miR-26b during the progression of cardiomyocyte differentiation from the P19 cell line. MATERIALS AND METHODS: The overexpression of miR-26b in P19 cells was performed by transduction with lentivirus vector...
August 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28732196/sam68-offers-selectively-aimed-modulation-of-transcription-in-cancer-stem-cells
#5
Kai Fu, Fengyi Wan
In this issue of Cell Chemical Biology,Benoit et al. (2017) report the selective targeting of cancer stem cells (CSCs) by the ICG-001/CWP family of molecules. Their findings reveal that Sam68 is a transcriptional modulator uniquely required for the dysregulated Wnt/β-catenin signaling in CSCs over healthy stem cells.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28648376/sam68-allows-selective-targeting-of-human-cancer-stem-cells
#6
Yannick D Benoit, Ryan R Mitchell, Ruth M Risueño, Luca Orlando, Borko Tanasijevic, Allison L Boyd, Lili Aslostovar, Kyle R Salci, Zoya Shapovalova, Jennifer Russell, Masakatsu Eguchi, Diana Golubeva, Monica Graham, Anargyros Xenocostas, Michael R Trus, Ronan Foley, Brian Leber, Tony J Collins, Mickie Bhatia
Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28578904/role-of-ras-wnt-%C3%AE-catenin-axis-activation-in-the-pathogenesis-of-podocyte-injury-and-tubulo-interstitial-nephropathy
#7
Lin Chen, Dan-Qian Chen, Ming Wang, Dan Liu, Hua Chen, Fang Dou, Nosratola D Vaziri, Ying-Yong Zhao
Renin-angiotensin system (RAS) plays a key role in the development and progression of chronic kidney disease (CKD). Recent studies have demonstrated activation of Wnt/β-catenin pathway by RAS in CKD. However, the underlying mechanisms of RAS and Wnt/β-catenin signaling interaction and their contribution to the pathogenesis of CKD have not been fully elucidated. Present study is designed to investigate the role of RAS/Wnt/β-catenin axis activation in tubulo-interstitial fibrosis and glomerulosclerosis by the cultured HK-2 and podocytes...
August 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28460484/the-%C3%AE-catenin-cbp-antagonist-icg-001-inhibits-pediatric-glioma-tumorigenicity-in-a-wnt-independent-manner
#8
Maria Wiese, Neele Walther, Christopher Diederichs, Fabian Schill, Sebastian Monecke, Gabriela Salinas, Dominik Sturm, Stefan M Pfister, Ralf Dressel, Steven A Johnsen, Christof M Kramm
Pediatric high-grade gliomas (pedHGG) belong to the most aggressive cancers in children with a poor prognosis due to a lack of efficient therapeutic strategies. The β-catenin/Wnt-signaling pathway was shown to hold promising potential as a treatment target in adult high-grade gliomas by abrogating tumor cell invasion and the acquisition of stem cell-like characteristics. Since pedHGG differ from their adult counterparts in genetically and biologically we aimed to investigate the effects of β-catenin/Wnt-signaling pathway-inhibition by the β-catenin/CBP antagonist ICG-001 in pedHGG cell lines...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405131/indocyanine-green-001-icg-001-attenuates-wnt-%C3%AE-catenin-induces-myocardial-injury-following-sepsis
#9
Nasser Ghaly Yousif, Najah R Hadi, Alaa Manea Hassan
OBJECTIVE: To investigate the mechanistic pathway of both indocyanine green (ICG)-001 in attenuated endotoxemia-induced cardiac depression through downregulation cardiac Wnt/ β-catenin cell signaling. MATERIALS AND METHODS: Adult (4-6 months) male Albino-Webster mice, their weights ranged from 25 to 30 g, were pretreated with ICG-001 i.p., following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a microcatheter system. Monocyte chemoattractant protein-1 (MCP-1) and cytokines mediators in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay...
January 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28302627/inhibition-of-smooth-muscle-%C3%AE-catenin-hinders-neointima-formation-after-vascular-injury
#10
Dario F Riascos-Bernal, Prameladevi Chinnasamy, Jordana N Gross, Vanessa Almonte, Lander Egaña-Gorroño, Dippal Parikh, Smitha Jayakumar, Liang Guo, Nicholas E S Sibinga
OBJECTIVE: Smooth muscle cells (SMCs) contribute to neointima formation after vascular injury. Although β-catenin expression is induced after injury, whether its function is essential in SMCs for neointimal growth is unknown. Moreover, although inhibitors of β-catenin have been developed, their effects on SMC growth have not been tested. We assessed the requirement for SMC β-catenin in short-term vascular homeostasis and in response to arterial injury and investigated the effects of β-catenin inhibitors on vascular SMC growth...
May 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28174691/beta-catenin-participates-in-dialysate-induced-peritoneal-fibrosis-via-enhanced-peritoneal-cell-epithelial-to-mesenchymal-transition
#11
Shuiyu Ji, Hao Deng, Wei Jin, Pengpeng Yan, Rending Wang, Lisha Pang, Jingyi Zhou, Jiaming Zhang, Xiaoying Chen, Xiang Zhao, Jia Shen
Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of β-catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg(-1) of the β-catenin inhibitor ICG-001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 μm ICG-001 (HG+ICG) for 48 h...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28088671/melatonin-attenuates-titanium-particle-induced-osteolysis-via-activation-of-wnt-%C3%AE-catenin-signaling-pathway
#12
Zichuan Ping, Xuanyang Hu, Liangliang Wang, Jiawei Shi, Yunxia Tao, Xiexing Wu, Zhenyang Hou, Xiaobin Guo, Wen Zhang, Huilin Yang, Yaozeng Xu, Zhirong Wang, Dechun Geng
Wear debris-induced inhibition of bone regeneration and extensive bone resorption were common features in peri-prosthetic osteolysis (PPO). Here, we investigated the effect of melatonin on titanium particle-stimulated osteolysis in a murine calvariae model and mouse-mesenchymal-stem cells (mMSCs) culture system. Melatonin inhibited titanium particle-induced osteolysis and increased bone formation at osteolytic sites, confirmed by radiological and histomorphometric data. Furthermore, osteoclast numbers decreased dramatically in the low- and high-melatonin administration mice, as respectively, compared with the untreated animals...
January 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/27909720/tetrandrine-inhibits-glioma-stem-like-cells-by-repressing-%C3%AE-catenin-expression
#13
Yong Zhang, Yu-Lin Wen, Ji-Wei Ma, Jie-Cheng Ye, Xiao Wang, Jian-Xian Huang, Chao-Yue Meng, Xiao-Ze Xu, Shao-Xiang Wang, Xue-Yun Zhong
Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27845386/mir-101-targets-the-ezh2-wnt-%C3%AE-catenin-the-pathway-to-promote-the-osteogenic-differentiation-of-human-bone-marrow-derived-mesenchymal-stem-cells
#14
Hongrui Wang, Yake Meng, Quanjun Cui, Fujun Qin, Haisong Yang, Yu Chen, Yajun Cheng, Jiangang Shi, Yongfei Guo
Mounting evidence indicates that microRNAs (miRNAs) are involved in multiple processes of osteogenic differentiation. MicroRNA-101 (miR-101), identified as a tumor suppressor, has been implicated in the pathogenesis of several types of cancer. However, the expression of miR-101 and its roles in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) remain unclear. We found that the miR-101 expression level was significantly increased during the osteogenic differentiation of hBMSCs...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27787561/%C3%AE-catenin-cbp-dependent-signaling-regulates-tgf-%C3%AE-induced-epithelial-to-mesenchymal-transition-of-lens-epithelial-cells
#15
Aftab Taiyab, Anna Korol, Paula A Deschamps, Judith A West-Mays
Purpose: Transforming growth factor-β-induced epithelial-mesenchymal transition (EMT) is one of the main causes of posterior capsular opacification (PCO) or secondary cataract; however, the signaling events involved in TGF-β-induced PCO have not been fully characterized. Here, we focus on examining the role of β-catenin/cyclic AMP response element-binding protein (CREB)-binding protein (CBP) and β-catenin/T-cell factor (TCF)-dependent signaling in regulating cytoskeletal dynamics during TGF-β-induced EMT in lens epithelial explants...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27712599/exosomes-derived-from-hypoxic-colorectal-cancer-cells-promote-angiogenesis-through-wnt4-induced-%C3%AE-catenin-signaling-in-endothelial-cells
#16
Zhe Huang, Yong Feng
Cancer cell-derived exosomes have been actively released into the tumor microenvironment with pleiotropic roles in tumor growth and metastasis, including angiogenesis and immune modulation. However, the functions and underlying mechanisms of exosomes shed by colorectal cancer (CRC) cells under hypoxic conditions remain unknown. Here we found that exosomes derived from hypoxic CRC cells promoted the proliferation and migration of endothelial cells. Suppression of exosome secretion through RAB27a knockdown in CRC cells inhibited exosomal-induced proliferation and migration of endothelial cells...
May 24, 2017: Oncology Research
https://www.readbyqxmd.com/read/27660676/cholangiocarcinoma-gone-without-the-wnt
#17
EDITORIAL
Anne Tr Noll, Thorsten Cramer, Steven Wm Olde Damink, Frank G Schaap
Cholangiocarcinoma (CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells...
September 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27629364/selective-targeting-of-creb-binding-protein-%C3%AE-catenin-inhibits-growth-of-and-extracellular-matrix-remodelling-by-airway-smooth-muscle
#18
Tim Koopmans, Stijn Crutzen, Mark H Menzen, Andrew J Halayko, Tillie-Louise Hackett, Darryl A Knight, Reinoud Gosens
BACKGROUND AND PURPOSE: Asthma is a heterogeneous chronic inflammatory disease, characterized by the development of structural changes (airway remodelling). β-catenin, a transcriptional co-activator, is fundamentally involved in airway smooth muscle growth and may be a potential target in the treatment of airway smooth muscle remodelling. EXPERIMENTAL APPROACH: We assessed the ability of small-molecule compounds that selectively target β-catenin breakdown or its interactions with transcriptional co-activators to inhibit airway smooth muscle remodelling in vitro and in vivo...
September 15, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27624805/blockade-of-%C3%AE-catenin-signaling-attenuates-toluene-diisocyanate-induced-experimental-asthma
#19
L Yao, H Zhao, H Tang, J Xiong, W Zhao, L Liu, H Dong, F Zou, S Cai
BACKGROUND: Aberrant activation of β-catenin signaling by both WNT-dependent and WNT-independent pathways has been demonstrated in asthmatic airways, which is thought to contribute critically in remodeling of the airways. Yet, the exact role of β-catenin in asthma is very poorly defined. As we have previously reported abnormal expression of β-catenin in a toluene diisocyanate (TDI)-induced asthma model, in this study, we evaluated the therapeutic efficacy of two small molecules XAV-939 and ICG-001 in TDI-asthmatic male BALB/c mice, which selectively block β-catenin-mediated transcription...
September 14, 2016: Allergy
https://www.readbyqxmd.com/read/27567978/wnt-%C3%AE-catenin-signaling-inhibitor-icg-001-enhances-pigmentation-of-cultured-melanoma-cells
#20
Kyung-Il Kim, Do-Sun Jeong, Eui Chang Jung, Jeung-Hoon Lee, Chang Deok Kim, Tae-Jin Yoon
BACKGROUND: Wnt/β-catenin signaling is important in development and differentiation of melanocytes. OBJECTIVE: The object of this study was to evaluate the effects of several Wnt/β-catenin signaling inhibitors on pigmentation using melanoma cells. METHODS: Melanoma cells were treated with Wnt/β-catenin signaling inhibitors, and then melanin content and tyrosinase activity were checked. RESULTS: Although some inhibitors showed slight inhibition of pigmentation, we failed to observe potential inhibitory effect of those chemicals on pigmentation of HM3KO melanoma cells...
November 2016: Journal of Dermatological Science
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