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Glucosamine and cancer

Lan V Pham, Jerry L Bryant, Richard Mendez, Juan Chen, Archito T Tamayo, Zijun Y Xu-Monette, Ken H Young, Ganiraju C Manyam, David Yang, L Jeffrey Medeiros, Richard J Ford
The hexosamine biosynthetic pathway (HBP) requires two key nutrients glucose and glutamine for O-linked N-acetylglucosamine (O-GlcNAc) cycling, a post-translational protein modification that adds GlcNAc to nuclear and cytoplasmic proteins. Increased GlcNAc has been linked to regulatory factors involved in cancer cell growth and survival. However, the biological significance of GlcNAc in diffuse large B-cell lymphoma (DLBCL) is not well defined. This study is the first to show that both the substrate and the endpoint O-GlcNAc transferase (OGT) enzyme of the HBP were highly expressed in DLBCL cell lines and in patient tumors compared with normal B-lymphocytes...
October 3, 2016: Oncotarget
Deep Pooja, Hitesh Kulhari, Madhusudana Kuncha, Shyam Sunder Rachamalla, David J Adams, Vipul Bansal, Ramakrishna Sistla
Oral delivery of anticancer drugs remains challenging despite the most convenient route of drug administration. Hydrophobicity and non-specific toxicities of anticancer agents are major impediments in the development of oral formulation. In this study, we developed wheat germ agglutinin (WGA)-conjugated, solid lipid nanoparticles to improve the oral delivery of the hydrophobic anticancer drug, paclitaxel (PTX). This study was focused to improve the PTX loading in biocompatible lipid matrix with high bioconjugation efficiency...
October 3, 2016: Molecular Pharmaceutics
Michal Rivlin, Gil Navon
The efficacy of glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) as agents for chemical exchange saturation transfer (CEST) magnetic resonance molecular imaging of tumors is demonstrated. Both agents reflect the metabolic activity and malignancy of the tumors. The method was tested in two types of tumors implanted orthotopically in mice: 4T1 (mouse mammary cancer cells) and MCF7 (human mammary cancer cells). 4T1 is a more aggressive type of tumor than MCF7 and exhibited a larger CEST effect. Two methods of administration of the agents, intravenous (IV) and oral (PO), gave similar results...
2016: Scientific Reports
Muobarak J Tuorkey
Exploiting the immune system to abolish cancer growth via vaccination is a promising strategy but that is limited by many clinical issues. For DNA vaccines, viral vectors as a delivery system mediate a strong immune response due to their protein structure, which could afflect the cellular uptake of the genetic vector or even induce cytotoxic immune responses against transfected cells. Recently, synthetic DNA delivery systems have been developed and recommended as much easier and simple approaches for DNA delivery compared with viral vectors...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Hemant K Patel, Virendra Gajbhiye, Prashant Kesharwani, Narendra K Jain
The present investigation was aimed at developing various ligands-anchored dendrimers and comparing their brain targeting potential at one platform. Sialic acid (S), glucosamine (G) and concanavalin A (C) anchored poly(propyleneimine) (PPI) dendritic nanoconjugates were developed and evaluated for delivery of anti-cancer drug, paclitaxel (PTX) to the brain. MTT assay on U373MG human astrocytoma cells indicated IC50 values of 0.40, 0.65, 0.95, 2.00 and 3.50μM for PTX loaded SPPI, GPPI, CPPI, PPI formulations, and free PTX, respectively...
November 15, 2016: Journal of Colloid and Interface Science
Saurav J Sarma, Aslam A Khan, Lalit N Goswami, Satish S Jalisatgi, M Frederick Hawthorne
The construction and application of a unique monodisperse closomer drug-delivery system (CDDS) integrating three different functionalities onto an icosahedral closo-dodecaborane [B12 ](2-) scaffold is described. Eleven B-OH vertices of [closo-B12 (OH)12 ](2-) were used to attach eleven copies of the anticancer drug chlorambucil and the targeting vector glucosamine through a bifurcating lysine linker. The remaining twelfth vertex was used to attach a fluorescent imaging probe. The presence of multiple glucosamine units offered a monodisperse and highly water-soluble CDDS with a high payload of therapeutic cargo...
August 26, 2016: Chemistry: a European Journal
Elizabeth D Kantor, Xuehong Zhang, Kana Wu, Lisa B Signorello, Andrew T Chan, Charles S Fuchs, Edward L Giovannucci
Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non-vitamin, non-mineral supplements and risk of CRC in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow-up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred...
November 1, 2016: International Journal of Cancer. Journal International du Cancer
Štěpán Horník, Lucie Červenková Šťastná, Petra Cuřínová, Jan Sýkora, Kateřina Káňová, Roman Hrstka, Ivana Císařová, Martin Dračínský, Jindřich Karban
BACKGROUND: Derivatives of D-glucosamine and D-galactosamine represent an important family of the cell surface glycan components and their fluorinated analogs found use as metabolic inhibitors of complex glycan biosynthesis, or as probes for the study of protein-carbohydrate interactions. This work is focused on the synthesis of acetylated 3-deoxy-3-fluoro, 4-deoxy-4-fluoro and 3,4-dideoxy-3,4-difluoro analogs of D-glucosamine and D-galactosamine via 1,6-anhydrohexopyranose chemistry...
2016: Beilstein Journal of Organic Chemistry
Akash K Kaushik, Ali Shojaie, Katrin Panzitt, Rajni Sonavane, Harene Venghatakrishnan, Mohan Manikkam, Alexander Zaslavsky, Vasanta Putluri, Vihas T Vasu, Yiqing Zhang, Ayesha S Khan, Stacy Lloyd, Adam T Szafran, Subhamoy Dasgupta, David A Bader, Fabio Stossi, Hangwen Li, Susmita Samanta, Xuhong Cao, Efrosini Tsouko, Shixia Huang, Daniel E Frigo, Lawrence Chan, Dean P Edwards, Benny A Kaipparettu, Nicholas Mitsiades, Nancy L Weigel, Michael Mancini, Sean E McGuire, Rohit Mehra, Michael M Ittmann, Arul M Chinnaiyan, Nagireddy Putluri, Ganesh S Palapattu, George Michailidis, Arun Sreekumar
The precise molecular alterations driving castration-resistant prostate cancer (CRPC) are not clearly understood. Using a novel network-based integrative approach, here, we show distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for CRPC. Expression of HBP enzyme glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is found to be significantly decreased in CRPC compared with localized prostate cancer (PCa). Genetic loss-of-function of GNPNAT1 in CRPC-like cells increases proliferation and aggressiveness, in vitro and in vivo...
2016: Nature Communications
Jennifer Lee, Eva-Maria Katzenmaier, Jürgen Kopitz, Johannes Gebert
Transforming growth factor-β (TGF-β) signaling plays a key role in regulating normal cell growth and differentiation, and mutations affecting members of this pathway contribute to cancer development and metastasis. In DNA mismatch repair (MMR)-deficient colorectal cancers that exhibit the microsatellite instability (MSI) phenotype, biallelic frameshift mutations in the transforming growth factor β receptor type 2 (TGFBR2) gene occur at high frequency that lead to altered signal transduction and downstream target gene expression...
August 2016: Cellular Signalling
Surendra R Punganuru, A G M Mostofa, Hanumantha Rao Madala, Debasish Basak, Kalkunte S Srivenugopal
Ethacrynic acid (EA), a known inhibitor of the neoplastic marker glutathione S-transferase P1 and other GSTs, exerts a weak antiproliferative activity against human cancer cells. The clinical use of EA (Edecrin) as an anticancer drug is limited by its potent loop diuretic activity. In this study, we developed a non-diuretic 2-amino-2-deoxy-d-glucose conjugated EA (EAG) to target tumors cells via the highly expressed glucose transporter 1 (GLUT1). Cell survival assays revealed that EAG had little effect on normal cells, but was cytotoxic 3 to 4...
June 15, 2016: Bioorganic & Medicinal Chemistry Letters
Gilbert Wasonga, Yota Tatara, Ikuko Kakizaki, Xuefei Huang
Elevated hyaluronan expression is a hallmark of many types of cancer. Therefore, inhibition of hyaluronan biosynthesis can potentially slow the growth of tumor cells. Herein, we explore a chain termination strategy to reduce hyaluronan synthesis by tumor cells. Several analogs of glucosamine were prepared, which contained modifications at the C-3 positions. These analogs can possibly cap the nonreducing end of a growing hyaluronan chain, thus lowering the amount of hyaluronan synthesized. Upon incubation with pancreatic cancer cells, a fluorine-containing glucosamine analog was found to exhibit significant inhibitory activities of hyaluronan synthesis...
2013: Journal of Carbohydrate Chemistry
Razieh Dalirfardouei, Gholamreza Karimi, Khadijeh Jamialahmadi
Glucosamine and its acetylated derivative, N-acetyl glucosamine, are naturally occurring amino sugars found in human body. They are important components of glycoproteins, proteoglycans and glycosaminoglycans. Scientific studies have supported that glucosamine has the beneficial pharmacological effects to relieve osteoarthritis symptoms. Glucosamine can also be as a promising candidate for the prevention and/or treatment of some other diseases due to its anti-oxidant and anti-inflammatory activities. Most of its function is exerted by modulation of inflammatory responses especially through Nuclear Factor-κB (NF-κB) that can control inflammatory cytokine production and cell survival...
May 1, 2016: Life Sciences
Patrick R Lawler, Akintunde O Akinkuolie, Paulette D Chandler, M Vinayaga Moorthy, Martin J Vandenburgh, Debra A Schaumberg, I-Min Lee, Robert J Glynn, Paul M Ridker, Julie E Buring, Samia Mora
RATIONALE: Circulating glycoprotein N-acetyl glucosamine residues have recently been associated with incident cardiovascular disease and diabetes mellitus. OBJECTIVE: Using a plasma glycan biosignature (GlycA) to identify circulating N-acetyl glycan groups, we examined the longitudinal association between GlycA and mortality among initially healthy individuals. METHODS AND RESULTS: We quantified GlycA by 400 MHz (1)H nuclear magnetic resonance spectroscopy in 27,524 participants in the Women's Health Study (NCT00000479)...
April 1, 2016: Circulation Research
Fuxing Zhou, Junwei Huo, Yu Liu, Haixia Liu, Gaowei Liu, Ying Chen, Biliang Chen
Endometrial cancer (EC) is one of the most common gynecological malignancies in the world. Associations between fasting glucose levels (greater than 5.6mmol/L) and the risk of cancer fatality have been reported. However, the underlying link between glucose metabolic disease and EC remains unclear. In the present study, we explored the influence of elevated glucose levels on the WNT/β-catenin pathway in EC. Previous studies have suggested that elevated concentrations of glucose can drive the hexosamine biosynthesis pathway (HBP) flux, thereby enhancing the O-GlcNAc modification of proteins...
May 2016: Journal of Steroid Biochemistry and Molecular Biology
Sanna Oikari, Katri Makkonen, Ashik Jawahar Deen, Ilari Tyni, Riikka Kärnä, Raija H Tammi, Markku I Tammi
UDP-N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a key substrate for the synthesis of glycoconjugates like hyaluronan, and as a metabolic sensor that controls cell functions through O-GlcNAc modification of intracellular proteins. However, little is known about the regulation of hexosamine biosynthesis that controls UDP-GlcNAc content. Four enzymes can catalyze the crucial starting point of the pathway, conversion of fructose-6-phosphate (Fru6P) to glucosamine-6-phosphate (GlcN6P): glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) and glucosamine-6-phosphate deaminases (GNPDA1 and 2)...
July 2016: Glycobiology
Smita Pawar, Ganesh Shevalkar, Pradeep Vavia
BACKGROUND: Efficacy of anticancer drug is limited due to non-selectivity and toxicities allied with the drug; therefore the heart of the present work is to formulate drug delivery systems targeted selectively towards cancer cells with minimal toxicity to normal cells. PURPOSE: Targeted drug delivery system of doxorubicin (DOX)-loaded niosomes using synthesized N-lauryl glucosamine (NLG) as a targeting ligand. METHODS: NLG-anchored DOX niosomes were developed using ethanol injection method...
September 2016: Journal of Drug Targeting
Yau Sang Chan, Lixin Xia, Tzi Bun Ng
A 60-kDa glucosamine binding lectin, white kidney bean lectin (WKBL), was purified from Phaseolus vulgaris cv. white kidney beans, by application of anion exchange chromatography on Q-Sepharose, affinity chromatography on Affi-gel blue gel, and FPLC-size exclusion on Superdex 75. The anti-proliferative activity of WKBL on HONE1 cells and HepG2 cells was stronger than the activity on MCF7 cells and WRL68 cells (IC50 values for a 48-h treatment with WKBL on HONE1 cells: 18.8 μM; HepG2 cells: 19.7 μM; MCF7 cells: 26...
April 2016: International Journal of Biological Macromolecules
Dong-Kwon Lim, Ryan G Wylie, Robert Langer, Daniel S Kohane
Vascular endothelial growth factor 165 (VEGF165) is an important extracellular protein involved in pathological angiogenesis in diseases such as cancer, wet age-related macular degeneration (wet-AMD) and retinitis pigmentosa. VEGF165 exists in two different isoforms: the angiogenic VEGF165a, and the anti-angiogenic VEGF165b. In some angiogenic diseases the proportion of VEGF165b may be equal to or higher than that of VEGF165a. Therefore, developing therapeutics that inhibit VEGF165a and not VEGF165b may result in greater anti-angiogenic activity and therapeutic benefit...
January 2016: Biomaterials
Jessica L Woodman, Min Sung Suh, Jianxing Zhang, Yuvabharath Kondaveeti, Diane J Burgess, Bruce A White, Glenn D Prestwich, Liisa T Kuhn
Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44(+)/CD24(-/low) human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP...
2015: International Journal of Cell Biology
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