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https://www.readbyqxmd.com/read/28693255/sodium-butyrate-enhances-the-growth-inhibitory-effect-of-sunitinib-in-human-renal-cell-carcinoma-cells
#1
Hiromi Sato, Miaki Uzu, Tatsuro Kashiba, Rina Suzuki, Takuya Fujiwara, Hiroko Okuzawa, Koichi Ueno
Sunitinib (SU) is a small molecule that inhibits the receptor tyrosine kinase (RTK) signaling pathway, and has been clinically used to treat advanced renal cell carcinoma (RCC). However, SU is not always effective as RCC is a highly chemoresistant type of cancer. One of the factors that confer chemoresistance to RCC is a hypoxic condition. Lack of oxygen activates hypoxia-inducible factor (HIF) protein, which is followed by the upregulation of growth factors, including vascular endothelial growth factor and activation of the RTK signaling pathway...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#2
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28674407/hdac6-a-novel-histone-deacetylase-implicated-in-pulmonary-arterial-hypertension
#3
Olivier Boucherat, Sophie Chabot, Roxane Paulin, Isabelle Trinh, Alice Bourgeois, François Potus, Marie-Claude Lampron, Caroline Lambert, Sandra Breuils-Bonnet, Valérie Nadeau, Renée Paradis, Elena A Goncharova, Steeve Provencher, Sébastien Bonnet
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with limited therapeutic options. Although exposed to stressful conditions, pulmonary artery (PA) smooth muscle cells (PASMCs) exhibit a "cancer-like" pro-proliferative and anti-apoptotic phenotype. HDAC6 is a cytoplasmic histone deacetylase regulating multiple pro-survival mechanisms and overexpressed in response to stress in cancer cells. Due to the similarities between cancer and PAH, we hypothesized that HDAC6 expression is increased in PAH-PASMCs to face stress allowing them to survive and proliferate, thus contributing to vascular remodeling in PAH...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28651835/andrographolide-reduced-vegfa-expression-in-hepatoma-cancer-cells-by-inactivating-hif-1%C3%AE-the-involvement-of-jnk-and-mta1-hdca
#4
Liang Shi, Guoqing Zhang, Zhiyong Zheng, Bin Lu, Lili Ji
Andrographolide (Andro) is the main active compound in medicinal herb Andrographis paniculata Nees (Acanthaceae). Vascular endothelial growth factor A (VEGFA), a key pro-angiogenic factor, contributes greatly to tumor growth. The purpose of this study is to observe the inhibition of Andro on VEGFA expression in hepatoma cancer cells and its engaged mechanism. Andro decreased mRNA and protein expression of VEGFA in hepatoma Hep3B and HepG2 cells. Andro also decreased hypoxia-inducible factor 1-alpha (HIF-1α) protein expression and its subsequent nuclear translocation...
June 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28648907/sulfated-dehydropolymer-of-caffeic-acid-in-vitro-anti-lung-cell-death-activity-and-in-vivo-intervention-in-emphysema-induced-by-vegf-receptor-blockade
#5
Tien M Truong, Hua Li, Sneha Dhapare, Umesh R Desai, Nobert F Voelkel, Masahiro Sakagami
Induced lung cell death and impaired hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) signaling are proposed as a pathobiologic mechanism for alveolar structural destruction and loss in emphysema. We hypothesized that our sulfated dehydropolymer of caffeic acid, CDSO3, exerts anti-cell death activities and therapeutic interventions in emphysema by virtue of Fe(2+) chelation-based HIF-1α/VEGF stabilization and elevation. The Fe(2+) chelating activity was determined in the chromogenic ferrozine-Fe(2+) chelation inhibitory assay...
June 22, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-type-2-diabetic-patients-with-target-hba1c-levels
#6
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D), however the underlining mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigates whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in T2D patients despite IGC...
June 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28611287/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#7
Chao Zhang, Chunzhang Yang, Michael J Feldman, Herui Wang, Ying Pang, Dominic M Maggio, Dongwang Zhu, Cody L Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O Brady, Karel Pacak, Zhengping Zhuang
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28606050/insights-into-the-targeting-potential-of-thymoquinone-for-therapeutic-intervention-against-triple-negative-breast-cancer
#8
Md Abul Barkat, Harshita Abul, Javed Ahmad, Mohammad Ahmed Khan, Sarwar Beg, Farhan Jalees Ahmad
BACKGROUND: Thymoquinone (TQ) is a bioactive phytoconstituent obtained from Nigella sativa (black seeds). It has promising potential in cancer prevention. OBJECTIVE: Previous studies have shown that TQ can modulate signaling pathways responsible for cancer progression, thus enhances the efficacy and improve safety profile of clinically used anticancer drugs. METHOD: TQ acts on cell cycle and inhibits progression from G1 to S phase by targeting various proteins (cyclin D1, cyclin E, and p27)...
June 11, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28588072/salt-inducible-kinase-induces-cytoplasmic-histone-deacetylase-4-to-promote-vascular-calcification
#9
Alon Abend, Omer Shkedi, Michal Fertouk, Lilac H Caspi, Izhak Kehat
A pathologic osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) promotes arterial calcifications, a process associated with significant morbidity and mortality. The molecular pathways promoting this pathology are not completely understood. We studied VSMCs, mouse aortic rings, and human aortic valves and showed here that histone deacetylase 4 (HDAC4) is upregulated early in the calcification process. Gain- and loss-of-function assays demonstrate that HDAC4 is a positive regulator driving this pathology...
July 2017: EMBO Reports
https://www.readbyqxmd.com/read/28576976/pleiotropic-and-adverse-effects-of-statins-do-epigenetics-play-a-role
#10
Stephanie C Allen, Cyril Ds Mamotte
Statins are widely used to prevent major cardiovascular events through the lowering of serum cholesterol. There is evidence that statins have pleiotropic effects, that is cholesterol-independent effects, that may also confer protection from cardiovascular disease and potentially numerous other pathologies including cancer. Statins also have a number of well described adverse effects including myopathy, rhabdomyolysis, liver damage and type 2 diabetes. This paper examines the evidence of epigenetic modifications as a contributory factor to the pleiotropic and adverse effects of statins...
June 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28485540/proteinase-activated-receptor-2-modulates-ve-cadherin-expression-to-affect-human-vascular-endothelial-barrier-function
#11
Rui Zhang, Jianjun Ge
Published data indicate that the protease-activated receptor (PAR) 2 is involved in the pathogenesis of some cardiovascular diseases; the underlying mechanism is to be further investigated. Ve-cadherin is a critical molecule in maintaining the endothelial barrier integrity. This study aims to investigate the role of PAR2 activation in compromising the cardiac endothelial barrier function. In this study, human umbilical vein endothelial cells (Huvec cells) were cultured into monolayers using as an in vitro model of barrier function...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28471989/valproic-acid-treatment-inhibits-vasopermeability-and-improves-survival-in-rats-with-lethal-scald-injury
#12
Fu-Bo Tang, Yue-Long Dai, Guo-Yong Zhou, Wen-Hua Zhang, Hai-Bin Wang, Yan-Guang Li, Rui-Liu, Hong-Min Luo, Sen Hu
The aim of this study was to examine whether administration of valproic acid (VPA), a histone deacetylase inhibitor, inhibits proinflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability evoking mediators. SD rats were subjected to a 50% TBSA full-thickness scald injury, and treated with either saline or VPA (300 mg/kg) intraperitoneally. Pulmonary vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), pulmonary microvascular permeability, water content, and acetylation of histone H3K9 of lungs were evaluated...
April 28, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28457391/cross-talk-between-sirtuin-1-and-high-mobility-box-1-in-steatotic-liver-graft-preservation
#13
M A Zaouali, A Panisello, A Lopez, E Folch, C Castro-Benítez, R Adam, J Roselló-Catafau
BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide +-dependent histone deacetylase that regulates various pathways involved in ischemia-reperfusion injury (IRI). Moreover, high-mobility group box 1 protein (HMGB1) has also been involved in inflammatory processes during IRI. However, the roles of both SIRT1 and HMGB1 in liver preservation is poorly understood. In this communication, we evaluated the potential relationship between SIRT1 and HMGB1 in steatotic and non-steatotic liver grafts preserved in Institute Georges Lopez solution (IGL-1) preservation solution enriched or not enriched with trimetazidine (TMZ)...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28411180/co-expression-of-sall4-with-hdac1-and-or-hdac2-is-associated-with-underexpression-of-pten-and-poor-prognosis-in-patients-with-hepatocellular-carcinoma
#14
Huanlin Wang, Kenichi Kohashi, Tomoharu Yoshizumi, Yukihiko Okumura, Yuki Tanaka, Masahiro Shimokawa, Takeshi Iwasaki, Shinichi Aishima, Yoshihiko Maehara, Yoshinao Oda
Spalt-like transcriptional factor 4 (SALL4), a stem marker, is re-activated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex (NuRD), which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study we investigated the expression status of SALL4, HDAC1 and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the post-hepatectomy specimens of 135 patients with hepatocellular carcinoma (HCC) who were treated at our hospital...
April 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28393178/b1-a-novel-hdac-inhibitor-induces-apoptosis-through-the-regulation-of-stat3-and-nf-%C3%AE%C2%BAb
#15
Meng-Hsuan Cheng, Yun-Hong Wong, Chia-Ming Chang, Chun-Chien Yang, Shih-Hua Chen, Chun-Lung Yuan, Hsiao-Mei Kuo, Chun-Yuh Yang, Hui-Fen Chiu
We previously demonstrated that B1 induced significant cytotoxic effects, cell cycle G1 arrest and apoptosis in human lung cancer A549 cells through the inhibition of DNA topoisomerase II activity. In the present study, we focused on the histone deacetylase (HDAC) modulation of B1 in A549 cells. HDACs, important enzymes affecting epigenetic regulation, play a crucial role in human carcinogenesis. Our findings showed that B1 could suppress the growth of A549 cells in vitro through the inhibition of HDAC activity...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28392885/the-transcription-factor-bach1-suppresses-the-developmental-angiogenesis-of-zebrafish
#16
Li Jiang, Meng Yin, Jie Xu, Mengping Jia, Shaoyang Sun, Xu Wang, Jianyi Zhang, Dan Meng
Bach1 disrupts Wnt/β-catenin signaling, reduces the proliferation, migration, and tube formation activity of endothelial cells (ECs), and suppresses angiogenesis in mice with surgically induced hind-limb ischemia (HLI). However, the function of Bach1 during developmental angiogenesis in zebrafish remains unclear. Here, we found that zebrafish Bach1 was expressed ubiquitously during early embryonic development in zebrafish. Bach1b mRNA injection of Tg(fli1:gfp) fish disrupted intersegmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) and suppressed endogenous Wnt/β-catenin signaling and Wnt8a stimulated vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) gene expression at early embryonic stages of zebrafish...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28338404/effect-of-histone-deacetylase-inhibitor-butyroyloxymethyl-diethyl-phosphate-an-7-on-corneal-neovascularization-in-a-mouse-model
#17
Michal Schaap-Fogler, Irit Bahar, Ada Rephaeli, Mor Dahbash, Abraham Nudelman, Eitan Livny, Tilda Barliya, Yael Nisgav, Tami Livnat
PURPOSE: To examine whether butyroyloxymethyl-diethyl phosphate (AN-7), a histone deacetylase inhibitor, inhibits chemically induced corneal neovascularization (NV) in mice. METHODS: Corneal NV was induced in the right eye of male C57BL mice by application of a mixture of 75% silver nitrate and 25% potassium nitrate to the corneal center. Immediately thereafter, the mice were randomized into 2 groups, receiving an intraperitoneal injection of AN-7 or saline, which served as control...
July 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28266122/histone-deacetylase-inhibitors-promote-enos-expression-in-vascular-smooth-muscle-cells-and-suppress-hypoxia-induced-cell-growth
#18
Xiaoling Tan, Lan Feng, Xiaoyong Huang, Yidong Yang, Chengzhong Yang, Yuqi Gao
Hypoxia stimulates excessive growth of vascular smooth muscle cells (VSMCs) contributing to vascular remodelling. Recent studies have shown that histone deacetylase inhibitors (HDIs) suppress VSMC proliferation and activate eNOS expression. However, the effects of HDI on hypoxia-induced VSMC growth and the role of activated eNOS in VSMCs are unclear. Using an EdU incorporation assay and flow cytometry analysis, we found that the HDIs, butyrate (Bur) and suberoylanilide hydroxamic acid (SAHA) significantly suppressed the proliferation of hypoxic VSMC lines and induced apoptosis...
March 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28251925/the-rhogap-protein-arhgap18-senex-localizes-to-microtubules-and-regulates-their-stability-in-endothelial-cells
#19
Michael D Lovelace, Elizabeth E Powter, Paul R Coleman, Yang Zhao, Amelia Parker, Garry H Chang, Angelina J Lay, Julie Hunter, Aaron P McGrath, Mika Jormakka, Patrick Bertolino, Geoffrey McCaughan, Maria Kavallaris, Mathew A Vadas, Jennifer R Gamble
RhoGTPases are important regulators of the cell cytoskeleton, controlling cell shape, migration and proliferation. Previously we showed that ARHGAP18 in endothelial cells is important in cell junctions. Here we show, using structured illumination microscopy (SIM), ground-state depletion (GSD), and total internal reflection fluorescence microscopy (TIRF) that a proportion of ARHGAP18 localizes to microtubules in endothelial cells, as well as in nonendothelial cells, an association confirmed biochemically. In endothelial cells, some ARHGAP18 puncta also colocalized to Weibel-Palade bodies on the microtubules...
April 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28243027/effects-of-histone-deacetylase-inhibitor-valproic-acid-on-the-expression-of-hypoxia-inducible-factor-1-alpha-in-human-retinal-m%C3%A3-ller-cells
#20
Young Jun Kim, Sang Jun Park, Na Rae Kim, Hee Seung Chin
PURPOSE: To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal Müller cells under hypoxic conditions. METHODS: Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasing concentrations of cobalt(II) chloride (CoCl2). Müller cells were also treated with a set concentration of CoCl2, along with various concentrations of VPA...
February 2017: Korean Journal of Ophthalmology: KJO
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