Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Unlocking the Potential of HK2 in Cancer Metabolism and Therapeutics

Author(s): Sara N. Garcia , Rita C. Guedes and M. Matilde Marques*

Volume 26, Issue 41, 2019

Page: [7285 - 7322] Pages: 38

DOI: 10.2174/0929867326666181213092652

Price: $65

Abstract

Glycolysis is a tightly regulated process in which several enzymes, such as Hexokinases (HKs), play crucial roles. Cancer cells are characterized by specific expression levels of several isoenzymes in different metabolic pathways and these features offer possibilities for therapeutic interventions. Overexpression of HKs (mostly of the HK2 isoform) have been consistently reported in numerous types of cancer. Moreover, deletion of HK2 has been shown to decrease cancer cell proliferation without explicit side effects in animal models, which suggests that targeting HK2 is a viable strategy for cancer therapy. HK2 inhibition causes a substantial decrease of glycolysis that affects multiple pathways of central metabolism and also destabilizes the mitochondrial outer membrane, ultimately enhancing cell death. Although glycolysis inhibition has met limited success, partly due to low selectivity for specific isoforms and excessive side effects of the reported HK inhibitors, there is ample ground for progress.

The current review is focused on HK2 inhibition, envisaging the development of potent and selective anticancer agents. The information on function, expression, and activity of HKs is presented, along with their structures, known inhibitors, and reported effects of HK2 ablation/inhibition. The structural features of the different isozymes are discussed, aiming to stimulate a more rational approach to the design of selective HK2 inhibitors with appropriate drug-like properties. Particular attention is dedicated to a structural and sequence comparison of the structurally similar HK1 and HK2 isoforms, aiming to unveil differences that could be explored therapeutically. Finally, several additional catalytic- and non-catalytic roles on different pathways and diseases, recently attributed to HK2, are reviewed and their implications briefly discussed.

Keywords: Hexokinases (HKs), cancer metabolism, cancer therapy, glycolysis, drug development, catalytic- and non-catalytic roles.

« Previous Next »
[1]
Petrelli, A.; Giordano, S. From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. Curr. Med. Chem., 2008, 15(5), 422-432.
[http://dx.doi.org/10.2174/092986708783503212] [PMID: 18288997]
[2]
Raghavendra, N.M.; Pingili, D.; Kadasi, S.; Mettu, A.; Prasad, S.V.U.M. Dual or multi-targeting inhibitors: The next generation anticancer agents. Eur. J. Med. Chem., 2018, 143(1), 1277-1300.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.021] [PMID: 29126724]
[3]
Ma, X.; Lv, X.; Zhang, J. Exploiting polypharmacology for improving therapeutic outcome of kinase inhibitors (KIs): An update of recent medicinal chemistry efforts. Eur. J. Med. Chem., 2018, 143, 449-463.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.049] [PMID: 29202407]
[4]
Zhong, J-T.; Zhou, S-H. Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma. Oncotarget, 2017, 8(8), 14133-14146.
[http://dx.doi.org/10.18632/oncotarget.13044] [PMID: 27823965]
[5]
Zhang, X.Y.; Zhang, M.; Cong, Q.; Zhang, M.X.; Zhang, M.Y.; Lu, Y.Y.; Xu, C.J. Hexokinase 2 confers resistance to cisplatin in ovarian cancer cells by enhancing cisplatin-induced autophagy. Int. J. Biochem. Cell Biol., 2018, 95, 9-16.
[http://dx.doi.org/10.1016/j.biocel.2017.12.010] [PMID: 29247711]
[6]
Hay, N. Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? Nat. Rev. Cancer, 2016, 16(10), 635-649.
[http://dx.doi.org/10.1038/nrc.2016.77] [PMID: 27634447]
[7]
Martinez-Outschoorn, U.E.; Peiris-Pagés, M.; Pestell, R.G.; Sotgia, F.; Lisanti, M.P. Cancer metabolism: a therapeutic perspective. Nat. Rev. Clin. Oncol., 2017, 14(1), 11-31.
[http://dx.doi.org/10.1038/nrclinonc.2016.60] [PMID: 27141887]
[8]
Han, J.; Zhang, L.; Guo, H.; Wysham, W.Z.; Roque, D.R.; Willson, A.K.; Sheng, X.; Zhou, C.; Bae-Jump, V.L. Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling. Gynecol. Oncol., 2015, 138(3), 668-675.
[http://dx.doi.org/10.1016/j.ygyno.2015.06.036] [PMID: 26135947]
[9]
Sun, L.; Yin, Y.; Clark, L.H.; Sun, W.; Sullivan, S.A.; Tran, A-Q.; Han, J.; Zhang, L.; Guo, H.; Madugu, E.; Pan, T.; Jackson, A.L.; Kilgore, J.; Jones, H.M.; Gilliam, T.P.; Zhou, C.; Bae-Jump, V.L. Dual inhibition of glycolysis and glutaminolysis as a therapeutic strategy in the treatment of ovarian cancer. Oncotarget, 2017, 8(38), 63551-63561.
[http://dx.doi.org/10.18632/oncotarget.18854] [PMID: 28969010]
[10]
Nelson, D.L.; Cox, M.M. Lehninger, Principles of Biochemistry, 4th ed; Freeman & Co.: New York, 2005.
[11]
Hu, J.; Locasale, J.W.; Bielas, J.H.; O’Sullivan, J.; Sheahan, K.; Cantley, L.C.; Vander Heiden, M.G.; Vitkup, D. Heterogeneity of tumor-induced gene expression changes in the human metabolic network. Nat. Biotechnol., 2013, 31(6), 522-529.
[http://dx.doi.org/10.1038/nbt.2530] [PMID: 23604282]
[12]
Wilson, J.E. Reviews of physiology, biochemistry and pharmacology;; Springer: Berlin, 1995, p. 126, pp. 65-198.
[13]
Irwin, D.M.; Tan, H. Molecular evolution of the vertebrate hexokinase gene family: Identification of a conserved fifth vertebrate hexokinase gene. Comp. Biochem. Physiol. Part D Genomics Proteomics, 2008, 3(1), 96-107.
[http://dx.doi.org/10.1016/j.cbd.2007.11.002] [PMID: 20483211]
[14]
Patra, K.C.; Wang, Q.; Bhaskar, P.T.; Miller, L.; Wang, Z.; Wheaton, W.; Chandel, N.; Laakso, M.; Muller, W.J.; Allen, E.L.; Jha, A.K.; Smolen, G.A.; Clasquin, M.F.; Robey, B.; Hay, N. Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell, 2013, 24(2), 213-228.
[http://dx.doi.org/10.1016/j.ccr.2013.06.014] [PMID: 23911236]
[15]
DeWaal, D.; Nogueira, V.; Terry, A.R.; Patra, K.C.; Jeon, S-M.; Guzman, G.; Au, J.; Long, C.P.; Antoniewicz, M.R.; Hay, N. Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin. Nat. Commun., 2018, 9(1), 446.
[http://dx.doi.org/10.1038/s41467-017-02733-4] [PMID: 29386513]
[16]
Camara, A.K.S.; Zhou, Y.; Wen, P.C.; Tajkhorshid, E.; Kwok, W.M. Mitochondrial VDAC1: A Key gatekeeper as potential therapeutic target. Front. Physiol., 2017, 8, 460.
[http://dx.doi.org/10.3389/fphys.2017.00460] [PMID: 28713289]
[17]
Vander Heiden, M.G.; DeBerardinis, R.J. Understanding the intersections between metabolism and cancer biology. Cell, 2017, 168(4), 657-669.
[http://dx.doi.org/10.1016/j.cell.2016.12.039] [PMID: 28187287]
[18]
Dwarakanath, B.; Jain, V. Targeting glucose metabolism with 2-deoxy-D-glucose for improving cancer therapy. Future Oncol., 2009, 5(5), 581-585.
[http://dx.doi.org/10.2217/fon.09.44] [PMID: 19519197]
[19]
Raez, L.E.; Papadopoulos, K.; Ricart, A.D.; Chiorean, E.G.; Dipaola, R.S.; Stein, M.N.; Rocha Lima, C.M.; Schlesselman, J.J.; Tolba, K.; Langmuir, V.K.; Kroll, S.; Jung, D.T.; Kurtoglu, M.; Rosenblatt, J.; Lampidis, T.J. A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors. Cancer Chemother. Pharmacol., 2013, 71(2), 523-530.
[http://dx.doi.org/10.1007/s00280-012-2045-1] [PMID: 23228990]
[20]
Threshold Pharmaceuticals Inc. Press Release: Phase 2 and Phase 3 Clinical Trials of TH-070 in Benign Prostatic Hyperplasia (BPH) Do Not Meet Primary Endpoint., 2006. May;12
[21]
Business Wire. PreScience Closes on Institutional Round of Financing, Available at: https://www.businesswire.com/news/home/20170426005840/en/PreScience-Closes-Institu-tional-Financing
[22]
Chen, Z.; Zhang, H.; Lu, W.; Huang, P. Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate. Biochim. Biophys. Acta, 2009, 1787(5), 553-560.
[http://dx.doi.org/10.1016/j.bbabio.2009.03.003] [PMID: 19285479]
[23]
Ning, X.; Qi, H.; Li, R.; Jin, Y.; McNutt, M.A.; Yin, Y. Synthesis and antitumor activity of novel 2, 3-didithiocarbamate substituted naphthoquinones as inhibitors of pyruvate kinase M2 isoform. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 126-129.
[http://dx.doi.org/10.1080/14756366.2017.1404591] [PMID: 29185365]
[24]
Lin, H.; Zeng, J.; Xie, R.; Schulz, M.J.; Tedesco, R.; Qu, J.; Erhard, K.F.; Mack, J.F.; Raha, K.; Rendina, A.R.; Szewczuk, L.M.; Kratz, P.M.; Jurewicz, A.J.; Cecconie, T.; Martens, S.; McDevitt, P.J.; Martin, J.D.; Chen, S.B.; Jiang, Y.; Nickels, L.; Schwartz, B.J.; Smallwood, A.; Zhao, B.; Campobasso, N.; Qian, Y.; Briand, J.; Rominger, C.M.; Oleykowski, C.; Hardwicke, M.A.; Luengo, J.I. Discovery of a novel 2,6-disubstituted glucosamine series of potent and selective hexokinase 2 inhibitors. ACS Med. Chem. Lett., 2015, 7(3), 217-222.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00214] [PMID: 26985301]
[25]
Amoedo, N.D.; Obre, E.; Rossignol, R. Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy. Biochim. Biophys. Acta Bioenerg., 2017, 1858(8), 674-685.
[http://dx.doi.org/10.1016/j.bbabio.2017.02.005] [PMID: 28213330]
[26]
Tran, Q.; Lee, H.; Park, J.; Kim, S.H.; Park, J. Targeting cancer metabolism - revisiting the Warburg effects. Toxicol. Res., 2016, 32(3), 177-193.
[http://dx.doi.org/10.5487/TR.2016.32.3.177] [PMID: 27437085]
[27]
Wolpaw, A.J.; Dang, C.V. Exploiting metabolic vulnerabilities of cancer with precision and accuracy. Trends Cell Biol., 2018, 28(3), 201-212.
[http://dx.doi.org/10.1016/j.tcb.2017.11.006] [PMID: 29229182]
[28]
Kroemer, G.; Pouyssegur, J. Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell, 2008, 13(6), 472-482.
[http://dx.doi.org/10.1016/j.ccr.2008.05.005] [PMID: 18538731]
[29]
Warburg, O. On the origin of cancer cells. Science, 1956, 123(3191), 309-314.
[http://dx.doi.org/10.1126/science.123.3191.309] [PMID: 13298683]
[30]
Zaidi, H.; Karakatsanis, N. Towards enhanced PET quantification in clinical oncology. Br. J. Radiol., 2018, 91(1081)20170508
[http://dx.doi.org/10.1259/bjr.20170508] [PMID: 29164924]
[31]
Liberti, M.V.; Locasale, J.W. The warburg effect: how does it benefit cancer cells? Trends Biochem. Sci., 2016, 41(3), 211-218.
[http://dx.doi.org/10.1016/j.tibs.2015.12.001] [PMID: 26778478]
[32]
Pathania, D.; Millard, M.; Neamati, N. Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism. Adv. Drug Deliv. Rev., 2009, 61(14), 1250-1275.
[http://dx.doi.org/10.1016/j.addr.2009.05.010] [PMID: 19716393]
[33]
Singh, D.; Arora, R.; Kaur, P.; Singh, B.; Mannan, R.; Arora, S. Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer. Cell Biosci., 2017, 7, 62.
[http://dx.doi.org/10.1186/s13578-017-0190-2] [PMID: 29158891]
[34]
Cervantes-Madrid, D.; Dueñas-González, A. Antitumor effects of a drug combination targeting glycolysis, glutaminolysis and de novo synthesis of fatty acids. Oncol. Rep., 2015, 34(3), 1533-1542.
[http://dx.doi.org/10.3892/or.2015.4077] [PMID: 26134042]
[35]
Pastorino, J.G.; Shulga, N.; Hoek, J.B. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J. Biol. Chem., 2002, 277(9), 7610-7618.
[http://dx.doi.org/10.1074/jbc.M109950200] [PMID: 11751859]
[36]
Arora, K.K.; Pedersen, P.L. Functional significance of mitochondrial bound hexokinase in tumor cell metabolism. Evidence for preferential phosphorylation of glucose by intramitochondrially generated ATP. J. Biol. Chem., 1988, 263(33), 17422-17428.
[PMID: 3182854]
[37]
Mazure, N.M. VDAC in cancer. Biochim. Biophys. Acta Bioenerg., 2017, 1858(8), 665-673.
[http://dx.doi.org/10.1016/j.bbabio.2017.03.002] [PMID: 28283400]
[38]
Gall, J.M.; Wong, V.; Pimental, D.R.; Havasi, A.; Wang, Z.; Pastorino, J.G.; Bonegio, R.G.B.; Schwartz, J.H.; Borkan, S.C. Hexokinase regulates Bax-mediated mitochondrial membrane injury following ischemic stress. Kidney Int., 2011, 79(11), 1207-1216.
[http://dx.doi.org/10.1038/ki.2010.532] [PMID: 21430642]
[39]
Shulga, N.; Wilson-Smith, R.; Pastorino, J.G. Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent mechanism. Cell Cycle, 2009, 8(20), 3355-3364.
[http://dx.doi.org/10.4161/cc.8.20.9853] [PMID: 19770592]
[40]
Pastorino, J.G.; Hoek, J.B. Hexokinase II: the integration of energy metabolism and control of apoptosis. Curr. Med. Chem., 2003, 10(16), 1535-1551.
[http://dx.doi.org/10.2174/0929867033457269] [PMID: 12871125]
[41]
Krasnov, G.S.; Dmitriev, A.A.; Lakunina, V.A.; Kirpiy, A.A.; Kudryavtseva, A.V. Targeting VDAC-bound hexokinase II: a promising approach for concomitant anti-cancer therapy. Expert Opin. Ther. Targets, 2013, 17(10), 1221-1233.
[http://dx.doi.org/10.1517/14728222.2013.833607] [PMID: 23984984]
[42]
Tidmarsh, G. Combination therapies for the treatment of cancer. WO2004064734A2, 2004.
[43]
Conway, L.P.; Voglmeir, J. Functional analysis of anomeric sugar kinases. Carbohydr. Res., 2016, 432, 23-30.
[http://dx.doi.org/10.1016/j.carres.2016.06.001] [PMID: 27351442]
[44]
Cárdenas, M.L.; Cornish-Bowden, A.; Ureta, T. Evolution and regulatory role of the hexokinases. Biochim. Biophys. Acta, 1998, 1401(3), 242-264.
[http://dx.doi.org/10.1016/S0167-4889(97)00150-X] [PMID: 9540816]
[45]
The UniProt Consortium. UniProt: the universal protein knowledgebase. Nucleic Acids Res., 2017, 45(D1), D158-D169.
[http://dx.doi.org/10.1093/nar/gkw1099] [PMID: 27899622]
[46]
González-Alvarez, R.; Ortega-Cuellar, D.; Hernández-Mendoza, A.; Moreno-Arriola, E.; Villaseñor-Mendoza, K.; Gálvez-Mariscal, A.; Pérez-Cruz, M.E.; Morales-Salas, I.; Velázquez-Arellano, A. The hexokinase gene family in the zebrafish: structure, expression, functional and phylogenetic analysis. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2009, 152(2), 189-195.
[http://dx.doi.org/10.1016/j.cbpb.2008.11.004] [PMID: 19087890]
[47]
Li, M.; Gao, Z.; Wang, Y.; Wang, H.; Zhang, S. Identification, expression and bioactivity of hexokinase in amphioxus: insights into evolution of vertebrate hexokinase genes. Gene, 2014, 535(2), 318-326.
[http://dx.doi.org/10.1016/j.gene.2013.10.068] [PMID: 24262936]
[48]
Griffin, L.D.; Gelb, B.D.; Wheeler, D.A.; Davison, D.; Adams, V.; McCabe, E.R.B. Mammalian hexokinase 1: evolutionary conservation and structure to function analysis. Genomics, 1991, 11(4), 1014-1024.
[http://dx.doi.org/10.1016/0888-7543(91)90027-C] [PMID: 1783373]
[49]
Tsai, H.J.; Wilson, J.E. Functional organization of mammalian hexokinases: both N- and C-terminal halves of the rat type II isozyme possess catalytic sites. Arch. Biochem. Biophys., 1996, 329(1), 17-23.
[http://dx.doi.org/10.1006/abbi.1996.0186] [PMID: 8619630]
[50]
Ahn, K.J.; Kim, J.; Yun, M.; Park, J.H.; Lee, J.D. Enzymatic properties of the N- and C-terminal halves of human hexokinase II. BMB Rep., 2009, 42(6), 350-355.
[http://dx.doi.org/10.5483/BMBRep.2009.42.6.350] [PMID: 19558793]
[51]
Ureta, T. The comparative isozymology of vertebrate hexokinases. Comp. Biochem. Physiol. B, 1982, 71(4), 549-555.
[http://dx.doi.org/10.1016/0305-0491(82)90461-8] [PMID: 7044667]
[52]
Wilson, J.E. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J. Exp. Biol., 2003, 206(Pt 12), 2049-2057.
[http://dx.doi.org/10.1242/jeb.00241] [PMID: 12756287]
[53]
Neary, C.L.; Pastorino, J.G. Nucleocytoplasmic shuttling of hexokinase II in a cancer cell. Biochem. Biophys. Res. Commun., 2010, 394(4), 1075-1081.
[http://dx.doi.org/10.1016/j.bbrc.2010.03.129] [PMID: 20346347]
[54]
Neary, C.L.; Pastorino, J.G. Akt inhibition promotes hexokinase 2 redistribution and glucose uptake in cancer cells. J. Cell. Physiol., 2013, 228(9), 1943-1948.
[http://dx.doi.org/10.1002/jcp.24361] [PMID: 23629924]
[55]
Robey, R.B.; Hay, N. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene, 2006, 25(34), 4683-4696.
[http://dx.doi.org/10.1038/sj.onc.1209595] [PMID: 16892082]
[56]
Tsai, H.J.; Wilson, J.E. Functional organization of mammalian hexokinases: characterization of the rat type III isozyme and its chimeric forms, constructed with the N- and C-terminal halves of the type I and type II isozymes. Arch. Biochem. Biophys., 1997, 338(2), 183-192.
[http://dx.doi.org/10.1006/abbi.1996.9850] [PMID: 9028870]
[57]
Postic, C.; Shiota, M.; Magnuson, M.A. Cell-specific roles of glucokinase in glucose homeostasis. Recent Prog. Horm. Res., 2001, 56, 195-217.
[http://dx.doi.org/10.1210/rp.56.1.195] [PMID: 11237213]
[58]
Sternisha, S.M.; Liu, P.; Marshall, A.G.; Miller, B.G. Mechanistic origins of enzyme activation in human glucokinase variants associated with congenital hyperinsulinism. Biochemistry, 2018, 57(10), 1632-1639.
[http://dx.doi.org/10.1021/acs.biochem.8b00022] [PMID: 29425029]
[59]
Chakera, A.J.; Steele, A.M.; Gloyn, A.L.; Shepherd, M.H.; Shields, B.; Ellard, S.; Hattersley, A.T. Recognition and management of individuals with hyperglycemia because of a heterozygous glucokinase mutation. Diabetes Care, 2015, 38(7), 1383-1392.
[http://dx.doi.org/10.2337/dc14-2769] [PMID: 26106223]
[60]
Haeusler, R.A.; Camastra, S.; Astiarraga, B.; Nannipieri, M.; Anselmino, M.; Ferrannini, E. Decreased expression of hepatic glucokinase in type 2 diabetes. Mol. Metab., 2014, 4(3), 222-226.
[http://dx.doi.org/10.1016/j.molmet.2014.12.007] [PMID: 25737948]
[61]
Lei, L.; Liu, S.; Li, Y.; Song, H.; He, L.; Liu, Q.; Sun, S.; Li, Y.; Feng, Z.; Shen, Z. The potential role of glucokinase activator SHP289-04 in anti-diabetes and hepatic protection. Eur. J. Pharmacol., 2018, 826, 17-23.
[http://dx.doi.org/10.1016/j.ejphar.2018.02.036] [PMID: 29477658]
[62]
Matschinsky, F.M. Assessing the potential of glucokinase activators in diabetes therapy. Nat. Rev. Drug Discov., 2009, 8(5), 399-416.
[http://dx.doi.org/10.1038/nrd2850] [PMID: 19373249]
[63]
Cheruvallath, Z.S.; Gwaltney, S.L., II; Sabat, M.; Tang, M.; Wang, H.; Jennings, A.; Hosfield, D.; Lee, B.; Wu, Y.; Halkowycz, P.; Grimshaw, C.E. Discovery of potent and orally active 1,4-disubstituted indazoles as novel allosteric glucokinase activators. Bioorg. Med. Chem. Lett., 2017, 27(12), 2678-2682.
[http://dx.doi.org/10.1016/j.bmcl.2017.04.041] [PMID: 28512030]
[64]
Toyoda, Y.; Tsuchida, A.; Iwami, E.; Shironoguchi, H.; Miwa, I. Regulation of hepatic glucose metabolism by translocation of glucokinase between the nucleus and the cytoplasm in hepatocytes. Horm. Metab. Res., 2001, 33(6), 329-336.
[http://dx.doi.org/10.1055/s-2001-15418] [PMID: 11456280]
[65]
Ali, A.; Wathes, D.C.; Swali, A.; Burns, H.; Burns, S. A novel mammalian glucokinase exhibiting exclusive inorganic polyphosphate dependence in the cell nucleus. Biochem. Biophys. Rep., 2017, 12, 151-157.
[http://dx.doi.org/10.1016/j.bbrep.2017.09.004] [PMID: 29090276]
[66]
Ronimus, R.S.; Morgan, H.W. Cloning and biochemical characterization of a novel mouse ADP-dependent glucokinase. Biochem. Biophys. Res. Commun., 2004, 315(3), 652-658.
[http://dx.doi.org/10.1016/j.bbrc.2004.01.103] [PMID: 14975750]
[67]
Guo, C.; Ludvik, A.E.; Arlotto, M.E.; Hayes, M.G.; Armstrong, L.L.; Scholtens, D.M.; Brown, C.D.; Newgard, C.B.; Becker, T.C.; Layden, B.T.; Lowe, W.L.; Reddy, T.E. Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat. Commun., 2015, 6, 6069.
[http://dx.doi.org/10.1038/ncomms7069] [PMID: 25648650]
[68]
Ludvik, A.E.; Pusec, C.M.; Priyadarshini, M.; Angueira, A.R.; Guo, C.; Lo, A.; Hershenhouse, K.S.; Yang, G.Y.; Ding, X.; Reddy, T.E.; Lowe, W.L., Jr; Layden, B.T. HKDC1 is a novel hexokinase involved in whole-body glucose use. Endocrinology, 2016, 157(9), 3452-3461.
[http://dx.doi.org/10.1210/en.2016-1288] [PMID: 27459389]
[69]
Hayes, M.G.; Urbanek, M.; Hivert, M.F.; Armstrong, L.L.; Morrison, J.; Guo, C.; Lowe, L.P.; Scheftner, D.A.; Pluzhnikov, A.; Levine, D.M.; McHugh, C.P.; Ackerman, C.M.; Bouchard, L.; Brisson, D.; Layden, B.T.; Mirel, D.; Doheny, K.F.; Leya, M.V.; Lown-Hecht, R.N.; Dyer, A.R.; Metzger, B.E.; Reddy, T.E.; Cox, N.J.; Lowe, W.L. Jr. HAPO study cooperative research group. Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. Diabetes, 2013, 62(9), 3282-3291.
[http://dx.doi.org/10.2337/db12-1692] [PMID: 23903356]
[70]
Kanthimathi, S.; Liju, S.; Laasya, D.; Anjana, R.M.; Mohan, V.; Radha, V. Hexokinase domain containing 1 (HKDC1) gene variants and their association with gestational diabetes mellitus in a south indian population. Ann. Hum. Genet., 2016, 80(4), 241-245.
[http://dx.doi.org/10.1111/ahg.12155] [PMID: 27346736]
[71]
Zhang, Z.; Huang, S.; Wang, H.; Wu, J.; Chen, D.; Peng, B.; Zhou, Q. High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma. Biochem. Biophys. Res. Commun., 2016, 474(4), 673-679.
[http://dx.doi.org/10.1016/j.bbrc.2016.05.007] [PMID: 27155152]
[72]
Li, G.H.; Huang, J.F. Inferring therapeutic targets from heterogeneous data: HKDC1 is a novel potential therapeutic target for cancer. Bioinformatics, 2014, 30(6), 748-752.
[http://dx.doi.org/10.1093/bioinformatics/btt606] [PMID: 24162464]
[73]
Anderson, C.M.; Stenkamp, R.E.; Steitz, T.A. Sequencing a protein by x-ray crystallography. II. Refinement of yeast hexokinase B co-ordinates and sequence at 2.1 A resolution. J. Mol. Biol., 1978, 123(1), 15-33.
[http://dx.doi.org/10.1016/0022-2836(78)90374-1] [PMID: 355643]
[74]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[75]
Nedyalkova, L.; Tong, Y.; Rabeh, W.; Tempel, W.; Landry, R.; Arrowsmith, C.H.; Edwards, A.M.; Bountra, C.; Weigelt, J.; Bochkarev, A.; Park, H. Structural Genomics Consortium (SGC). Crystal structure of the C-terminal hexokinase domain of human HK3. RSCB PDB - 3HM8; Released, 2009, pp. 8-11.
[76]
Ardehali, H.; Yano, Y.; Printz, R.L.; Koch, S.; Whitesell, R.R.; May, J.M.; Granner, D.K. Functional organization of mammalian hexokinase II. Retention of catalytic and regulatory functions in both the NH2- and COOH-terminal halves. J. Biol. Chem., 1996, 271(4), 1849-1852.
[http://dx.doi.org/10.1074/jbc.271.4.1849] [PMID: 8567628]
[77]
Rabeh, W. M.; Zhu, H.; Nedyalkova, L.; Tempel, W.; Wasney, G.; Landry, R.; Vedadi, M.; Arrowsmith, C. H.; Edwards, A. M.; Sundstrom, M.; Weigelt, J.; Bochkarev, A.; Park, H. Crystal structure of human hexokinase II. RSCB PDB - 2NZT; Released, 2006, 5 December.
[78]
Mulichak, A.M.; Wilson, J.E.; Padmanabhan, K.; Garavito, R.M. The structure of mammalian hexokinase-1. Nat. Struct. Biol., 1998, 5(7), 555-560.
[http://dx.doi.org/10.1038/811] [PMID: 9665168]
[79]
Kuser, P.; Cupri, F.; Bleicher, L.; Polikarpov, I. Crystal structure of yeast hexokinase PI in complex with glucose: A classical “induced fit” example revised. Proteins, 2008, 72(2), 731-740.
[http://dx.doi.org/10.1002/prot.21956] [PMID: 18260108]
[80]
Feng, J.; Zhao, S.; Chen, X.; Wang, W.; Dong, W.; Chen, J.; Shen, J.R.; Liu, L.; Kuang, T. Biochemical and structural study of Arabidopsis hexokinase 1. Acta Crystallogr. D Biol. Crystallogr., 2015, 71(Pt 2), 367-375.
[http://dx.doi.org/10.1107/S1399004714026091] [PMID: 25664748]
[81]
Steitz, T.A.; Shoham, M.; Bennett, W.S. Jr. Structural dynamics of yeast hexokinase during catalysis. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1981, 293(1063), 43-52.
[http://dx.doi.org/10.1098/rstb.1981.0058] [PMID: 6115422]
[82]
Aleshin, A.E.; Zeng, C.; Bartunik, H.D.; Fromm, H.J.; Honzatko, R.B. Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate. J. Mol. Biol., 1998, 282(2), 345-357.
[http://dx.doi.org/10.1006/jmbi.1998.2017] [PMID: 9735292]
[83]
Petit, P.; Antoine, M.; Ferry, G.; Boutin, J.A.; Lagarde, A.; Gluais, L.; Vincentelli, R.; Vuillard, L. The active conformation of human glucokinase is not altered by allosteric activators. Acta Crystallogr. D Biol. Crystallogr., 2011, 67(Pt 11), 929-935.
[http://dx.doi.org/10.1107/S0907444911036729] [PMID: 22101819]
[84]
Liu, S.; Ammirati, M.J.; Song, X.; Knafels, J.D.; Zhang, J.; Greasley, S.E.; Pfefferkorn, J.A.; Qiu, X. Insights into mechanism of glucokinase activation: observation of multiple distinct protein conformations. J. Biol. Chem., 2012, 287(17), 13598-13610.
[http://dx.doi.org/10.1074/jbc.M111.274126] [PMID: 22298776]
[85]
Rosano, C.; Sabini, E.; Rizzi, M.; Deriu, D.; Murshudov, G.; Bianchi, M.; Serafini, G.; Magnani, M.; Bolognesi, M. Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control. Structure, 1999, 7(11), 1427-1437.
[http://dx.doi.org/10.1016/S0969-2126(00)80032-5] [PMID: 10574795]
[86]
Smith, T.A.D. Mammalian hexokinases and their abnormal expression in cancer. Br. J. Biomed. Sci., 2000, 57(2), 170-178.
[PMID: 10912295]
[87]
Osawa, H.; Sutherland, C.; Robey, R.B.; Printz, R.L.; Granner, D.K. Analysis of the signaling pathway involved in the regulation of hexokinase II gene transcription by insulin. J. Biol. Chem., 1996, 271(28), 16690-16694.
[http://dx.doi.org/10.1074/jbc.271.28.16690] [PMID: 8663315]
[88]
Osawa, H.; Robey, R.B.; Printz, R.L.; Granner, D.K. Identification and characterization of basal and cyclic AMP response elements in the promoter of the rat hexokinase II gene. J. Biol. Chem., 1996, 271(29), 17296-17303.
[http://dx.doi.org/10.1074/jbc.271.29.17296] [PMID: 8663388]
[89]
Katagiri, M.; Karasawa, H.; Takagi, K.; Nakayama, S.; Yabuuchi, S.; Fujishima, F.; Naitoh, T.; Watanabe, M.; Suzuki, T.; Unno, M.; Sasano, H. Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration. Histol. Histopathol., 2017, 32(4), 351-360.
[http://dx.doi.org/10.14670/HH-11-799] [PMID: 27363977]
[90]
Wu, J.; Hu, L.; Wu, F.; Zou, L.; He, T. Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis. Oncotarget, 2017, 8(19), 32332-32344.
[http://dx.doi.org/10.18632/oncotarget.15974] [PMID: 28415659]
[91]
Zhang, Z.F.; Feng, X.S.; Chen, H.; Duan, Z.J.; Wang, L.X.; Yang, D.; Liu, P.X.; Zhang, Q.P.; Jin, Y.L.; Sun, Z.G.; Liu, H. Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection. BMC Gastroenterol., 2016, 16(1), 57.
[http://dx.doi.org/10.1186/s12876-016-0474-8] [PMID: 27255554]
[92]
Thamrongwaranggoon, U.; Seubwai, W.; Phoomak, C.; Sangkhamanon, S.; Cha’on, U.; Boonmars, T.; Wongkham, S. Targeting hexokinase II as a possible therapy for cholangiocarcinoma. Biochem. Biophys. Res. Commun., 2017, 484(2), 409-415.
[http://dx.doi.org/10.1016/j.bbrc.2017.01.139] [PMID: 28131825]
[93]
Kharitonov, S.; Zikiriahodzhaev, A.; Ermoshchenkova, M.; Sukhot’ko, A.; Fedorova, M.; Pudova, E.; Alekseev, B.; Kaprin, A.; Kudryavtseva, A. Hexokinases in breast cancer. Int. J. Biosci. Biotechnol., 2017, 4(2), 110-116.
[http://dx.doi.org/10.24843/IJBB.2017.v04.i02.p05]
[94]
Wang, H.; Wang, L.; Zhang, Y.; Wang, J.; Deng, Y.; Lin, D. Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth. Cancer Cell Int., 2016, 16, 9.
[http://dx.doi.org/10.1186/s12935-016-0280-y] [PMID: 26884725]
[95]
Kim, J.W.; Gao, P.; Liu, Y.C.; Semenza, G.L.; Dang, C.V. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol. Cell. Biol., 2007, 27(21), 7381-7393.
[http://dx.doi.org/10.1128/MCB.00440-07] [PMID: 17785433]
[96]
Gwak, G.Y.; Yoon, J.H.; Kim, K.M.; Lee, H.S.; Chung, J.W.; Gores, G.J. Hypoxia stimulates proliferation of human hepatoma cells through the induction of hexokinase II expression. J. Hepatol., 2005, 42(3), 358-364.
[http://dx.doi.org/10.1016/j.jhep.2004.11.020] [PMID: 15710218]
[97]
Ha, J.H.; Radhakrishnan, R.; Jayaraman, M.; Yan, M.; Ward, J.D.; Fung, K.M.; Moxley, K.; Sood, A.K.; Isidoro, C.; Mukherjee, P.; Song, Y.S.; Dhanasekaran, D.N. LPA induces metabolic reprogramming in ovarian cancer via a pseudohypoxic response. Cancer Res., 2018, 78(8), 1923-1934.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-1624] [PMID: 29386184]
[98]
Sun, Z.; Zhang, W.; Li, Q. miR-125a suppresses viability and glycolysis and induces apoptosis by targeting Hexokinase 2 in laryngeal squamous cell carcinoma. Cell Biosci., 2017, 7, 51.
[http://dx.doi.org/10.1186/s13578-017-0178-y] [PMID: 29043013]
[99]
Gregersen, L.H.; Jacobsen, A.; Frankel, L.B.; Wen, J.; Krogh, A.; Lund, A.H. MicroRNA-143 down-regulates Hexokinase 2 in colon cancer cells. BMC Cancer, 2012, 12, 232.
[http://dx.doi.org/10.1186/1471-2407-12-232] [PMID: 22691140]
[100]
Lu, C.L.; Qin, L.; Liu, H.C.; Candas, D.; Fan, M.; Li, J.J. Tumor cells switch to mitochondrial oxidative phosphorylation under radiation via mTOR-mediated hexokinase II inhibition--a Warburg-reversing effect. PLoS One, 2015, 10(3)e0121046
[http://dx.doi.org/10.1371/journal.pone.0121046] [PMID: 25807077]
[101]
Roberts, D.J.; Tan-Sah, V.P.; Ding, E.Y.; Smith, J.M.; Miyamoto, S. Hexokinase-II positively regulates glucose starvation-induced autophagy through TORC1 inhibition. Mol. Cell, 2014, 53(4), 521-533.
[http://dx.doi.org/10.1016/j.molcel.2013.12.019] [PMID: 24462113]
[102]
Roberts, D.J.; Tan-Sah, V.P.; Smith, J.M.; Miyamoto, S. Akt phosphorylates HK-II at Thr-473 and increases mitochondrial HK-II association to protect cardiomyocytes. J. Biol. Chem., 2013, 288(33), 23798-23806.
[http://dx.doi.org/10.1074/jbc.M113.482026] [PMID: 23836898]
[103]
Kolar, D.; Gresikova, M.; Waskova-Arnostova, P.; Elsnicova, B.; Kohutova, J.; Hornikova, D.; Vebr, P.; Neckar, J.; Blahova, T.; Kasparova, D.; Novotny, J.; Kolar, F.; Novakova, O.; Zurmanova, J.M. Adaptation to chronic continuous hypoxia potentiates Akt/HK2 anti-apoptotic pathway during brief myocardial ischemia/reperfusion insult. Mol. Cell. Biochem., 2017, 432(1-2), 99-108.
[http://dx.doi.org/10.1007/s11010-017-3001-5] [PMID: 28290047]
[104]
Hu, J.W.; Sun, P.; Zhang, D.X.; Xiong, W.J.; Mi, J. Hexokinase 2 regulates G1/S checkpoint through CDK2 in cancer-associated fibroblasts. Cell. Signal., 2014, 26(10), 2210-2216.
[http://dx.doi.org/10.1016/j.cellsig.2014.04.015] [PMID: 24780297]
[105]
Mamede, M.; Higashi, T.; Kitaichi, M.; Ishizu, K.; Ishimori, T.; Nakamoto, Y.; Yanagihara, K.; Li, M.; Tanaka, F.; Wada, H.; Manabe, T.; Saga, T. [18F]FDG uptake and PCNA, Glut-1, and Hexokinase-II expressions in cancers and inflammatory lesions of the lung. Neoplasia, 2005, 7(4), 369-379.
[http://dx.doi.org/10.1593/neo.04577] [PMID: 15967114]
[106]
Wang, L.; Xiong, H.; Wu, F.; Zhang, Y.; Wang, J.; Zhao, L.; Guo, X.; Chang, L.J.; Zhang, Y.; You, M.J.; Koochekpour, S.; Saleem, M.; Huang, H.; Lu, J.; Deng, Y. Hexokinase 2-mediated Warburg effect is required for PTEN- and p53-deficiency-driven prostate cancer growth. Cell Rep., 2014, 8(5), 1461-1474.
[http://dx.doi.org/10.1016/j.celrep.2014.07.053] [PMID: 25176644]
[107]
Lin, Y.H.; Wu, M.H.; Huang, Y.H.; Yeh, C.T.; Cheng, M.L.; Chi, H.C.; Tsai, C.Y.; Chung, I.H.; Chen, C.Y.; Lin, K.H. Taurine up-regulated gene 1 functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma. Hepatology, 2018, 67(1), 188-203.
[http://dx.doi.org/10.1002/hep.29462] [PMID: 28802060]
[108]
Singh, A.; Sen, E. Reciprocal role of SIRT6 and Hexokinase 2 in the regulation of autophagy driven monocyte differentiation. Exp. Cell Res., 2017, 360(2), 365-374.
[http://dx.doi.org/10.1016/j.yexcr.2017.09.028] [PMID: 28935467]
[109]
Xia, H.G.; Najafov, A.; Geng, J.; Galan-Acosta, L.; Han, X.; Guo, Y.; Shan, B.; Zhang, Y.; Norberg, E.; Zhang, T.; Pan, L.; Liu, J.; Coloff, J.L.; Ofengeim, D.; Zhu, H.; Wu, K.; Cai, Y.; Yates, J.R.; Zhu, Z.; Yuan, J.; Vakifahmetoglu-Norberg, H. Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death. J. Cell Biol., 2015, 210(5), 705-716.
[http://dx.doi.org/10.1083/jcb.201503044] [PMID: 26323688]
[110]
Xiao, M.; Lou, C.; Xiao, H.; Yang, Y.; Cai, X.; Li, C.; Jia, S.; Huang, Y. MiR-128 regulation of glucose metabolism and cell proliferation in triple-negative breast cancer. Br. J. Surg., 2018, 105(1), 75-85.
[http://dx.doi.org/10.1002/bjs.10646] [PMID: 29116653]
[111]
Liu, G.; Li, Y.I.; Gao, X. Overexpression of microRNA-133b sensitizes non-small cell lung cancer cells to irradiation through the inhibition of glycolysis. Oncol. Lett., 2016, 11(4), 2903-2908.
[http://dx.doi.org/10.3892/ol.2016.4316] [PMID: 27073574]
[112]
Zhao, X.; Lu, C.; Chu, W.; Zhang, B.; Zhen, Q.; Wang, R.; Zhang, Y.; Li, Z.; Lv, B.; Li, H.; Liu, J. MicroRNA-124 suppresses proliferation and glycolysis in non-small cell lung cancer cells by targeting AKT-GLUT1/HKII. Tumour Biol., 2017, 39(5)1010428317706215
[http://dx.doi.org/10.1177/1010428317706215] [PMID: 28488541]
[113]
Tao, T.; Chen, M.; Jiang, R.; Guan, H.; Huang, Y.; Su, H.; Hu, Q.; Han, X.; Xiao, J. Involvement of EZH2 in aerobic glycolysis of prostate cancer through miR-181b/HK2 axis. Oncol. Rep., 2017, 37(3), 1430-1436.
[http://dx.doi.org/10.3892/or.2017.5430] [PMID: 28184935]
[114]
Li, L.Q.; Yang, Y.; Chen, H.; Zhang, L.; Pan, D.; Xie, W.J. MicroRNA-181b inhibits glycolysis in gastric cancer cells via targeting hexokinase 2 gene. Cancer Biomark., 2016, 17(1), 75-81.
[http://dx.doi.org/10.3233/CBM-160619] [PMID: 27314295]
[115]
Qin, Y.; Cheng, C.; Lu, H.; Wang, Y. miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells. Biochem. Biophys. Res. Commun., 2016, 469(1), 37-43.
[http://dx.doi.org/10.1016/j.bbrc.2015.11.066] [PMID: 26607110]
[116]
Jiang, S.; Yan, W.; Wang, S.E.; Baltimore, D. Let-7 Suppresses B cell activation through restricting the availability of necessary nutrients. Cell Metab, 2018, 27(2), 393-403, e4.
[http://dx.doi.org/10.1016/j.cmet.2017.12.007] [PMID: 29337138]
[117]
Zhang, J.; Wang, S.; Jiang, B.; Huang, L.; Ji, Z.; Li, X.; Zhou, H.; Han, A.; Chen, A.; Wu, Y.; Ma, H.; Zhao, W.; Zhao, Q.; Xie, C.; Sun, X.; Zhou, Y.; Huang, H.; Suleman, M.; Lin, F.; Zhou, L.; Tian, F.; Jin, M.; Cai, Y.; Zhang, N.; Li, Q. c-Src phosphorylation and activation of hexokinase promotes tumorigenesis and metastasis. Nat. Commun., 2017, 8, 13732.
[http://dx.doi.org/10.1038/ncomms13732] [PMID: 28054552]
[118]
Huang, Y.P.; Chang, N.W. Proteomic analysis of oral cancer reveals new potential therapeutic targets involved in the Warburg effect. Clin. Exp. Pharmacol. Physiol., 2017, 44(8), 880-887.
[http://dx.doi.org/10.1111/1440-1681.12774] [PMID: 28453233]
[119]
Huang, X.; Liu, M.; Sun, H.; Wang, F.; Xie, X.; Chen, X.; Su, J.; He, Y.; Dai, Y.; Wu, H.; Shen, L. HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma. Int. J. Clin. Exp. Pathol., 2015, 8(4), 4054-4063.
[PMID: 26097593]
[120]
Hamabe, A.; Yamamoto, H.; Konno, M.; Uemura, M.; Nishimura, J.; Hata, T.; Takemasa, I.; Mizushima, T.; Nishida, N.; Kawamoto, K.; Koseki, J.; Doki, Y.; Mori, M.; Ishii, H. Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase-E1α in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis. Cancer Sci., 2014, 105(9), 1100-1108.
[http://dx.doi.org/10.1111/cas.12487] [PMID: 25060325]
[121]
Qiu, M.Z.; Han, B.; Luo, H.Y.; Zhou, Z.W.; Wang, Z.Q.; Wang, F.H.; Li, Y.H.; Xu, R.H. Expressions of hypoxia-inducible factor-1α and hexokinase-II in gastric adenocarcinoma: the impact on prognosis and correlation to clinicopathologic features. Tumour Biol., 2011, 32(1), 159-166.
[http://dx.doi.org/10.1007/s13277-010-0109-6] [PMID: 20845004]
[122]
Gong, L.; Cui, Z.; Chen, P.; Han, H.; Peng, J.; Leng, X. Reduced survival of patients with hepatocellular carcinoma expressing hexokinase II. Med. Oncol., 2012, 29(2), 909-914.
[http://dx.doi.org/10.1007/s12032-011-9841-z] [PMID: 21279699]
[123]
Palmieri, D.; Fitzgerald, D.; Shreeve, S.M.; Hua, E.; Bronder, J.L.; Weil, R.J.; Davis, S.; Stark, A.M.; Merino, M.J.; Kurek, R.; Mehdorn, H.M.; Davis, G.; Steinberg, S.M.; Meltzer, P.S.; Aldape, K.; Steeg, P.S. Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis. Mol. Cancer Res., 2009, 7(9), 1438-1445.
[http://dx.doi.org/10.1158/1541-7786.MCR-09-0234] [PMID: 19723875]
[124]
Deng, Y.; Lu, J. Targeting hexokinase 2 in castration-resistant prostate cancer. Mol. Cell. Oncol., 2015, 2(3)e974465
[http://dx.doi.org/10.4161/23723556.2014.974465] [PMID: 27308450]
[125]
Sato-Tadano, A.; Suzuki, T.; Amari, M.; Takagi, K.; Miki, Y.; Tamaki, K.; Watanabe, M.; Ishida, T.; Sasano, H.; Ohuchi, N. Hexokinase II in breast carcinoma: a potent prognostic factor associated with hypoxia-inducible factor-1α and Ki-67. Cancer Sci., 2013, 104(10), 1380-1388.
[http://dx.doi.org/10.1111/cas.12238] [PMID: 23869589]
[126]
Xi, F.; Ye, J. Inhibition of lung carcinoma A549 cell growth by knockdown of hexokinase 2 in situ and in vivo. Oncol. Res., 2016, 23(1-2), 53-59.
[http://dx.doi.org/10.3727/096504015X14459480491740] [PMID: 26802651]
[127]
Peng, Q.P.; Zhou, J.M.; Zhou, Q.; Pan, F.; Zhong, D.P.; Liang, H.J. Downregulation of the hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil. Chemotherapy, 2008, 54(5), 357-363.
[http://dx.doi.org/10.1159/000153655] [PMID: 18772588]
[128]
Liu, Y.; Murray-Stewart, T.; Casero, R.A. Jr.; Kagiampakis, I.; Jin, L.; Zhang, J.; Wang, H.; Che, Q.; Tong, H.; Ke, J.; Jiang, F.; Wang, F.; Wan, X. Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int. J. Oncol., 2017, 50(6), 2011-2023.
[http://dx.doi.org/10.3892/ijo.2017.3979] [PMID: 28498475]
[129]
Wu, J.; Zhang, X.; Wang, Y.; Sun, Q.; Chen, M.; Liu, S.; Zou, X. Licochalcone A suppresses hexokinase 2-mediated tumor glycolysis in gastric cancer via downregulation of the Akt signaling pathway. Oncol. Rep., 2018, 39(3), 1181-1190.
[http://dx.doi.org/10.3892/or.2017.6155] [PMID: 29286170]
[130]
Xu, D.; Jin, J.; Yu, H.; Zhao, Z.; Ma, D.; Zhang, C.; Jiang, H. Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2. J. Exp. Clin. Cancer Res., 2017, 36(1), 44.
[http://dx.doi.org/10.1186/s13046-017-0514-4] [PMID: 28320429]
[131]
Dai, W.; Wang, F.; Lu, J.; Xia, Y.; He, L.; Chen, K.; Li, J.; Li, S.; Liu, T.; Zheng, Y.; Wang, J.; Lu, W.; Zhou, Y.; Yin, Q.; Abudumijiti, H.; Chen, R.; Zhang, R.; Zhou, L.; Zhou, Z.; Zhu, R.; Yang, J.; Wang, C.; Zhang, H.; Zhou, Y.; Xu, L.; Guo, C. By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice. Oncotarget, 2015, 6(15), 13703-13717.
[http://dx.doi.org/10.18632/oncotarget.3800] [PMID: 25938543]
[132]
Gao, X.; Han, H. Jolkinolide B inhibits glycolysis by downregulating hexokinase 2 expression through inactivating the Akt/mTOR pathway in non-small cell lung cancer cells. J. Cell. Biochem., 2018, 119(6), 4967-4974.
[http://dx.doi.org/10.1002/jcb.26742] [PMID: 29384225]
[133]
Chen, G.Q.; Tang, C.F.; Shi, X.K.; Lin, C.Y.; Fatima, S.; Pan, X.H.; Yang, D.J.; Zhang, G.; Lu, A.P.; Lin, S.H.; Bian, Z.X. Halofuginone inhibits colorectal cancer growth through suppression of Akt/mTORC1 signaling and glucose metabolism. Oncotarget, 2015, 6(27), 24148-24162.
[http://dx.doi.org/10.18632/oncotarget.4376] [PMID: 26160839]
[134]
Wei, L.; Dai, Q.; Zhou, Y.; Zou, M.; Li, Z.; Lu, N.; Guo, Q. Oroxylin A sensitizes non-small cell lung cancer cells to anoikis via glucose-deprivation-like mechanisms: c-Src and hexokinase II. Biochim. Biophys. Acta, 2013, 1830(6), 3835-3845.
[http://dx.doi.org/10.1016/j.bbagen.2013.03.009] [PMID: 23500080]
[135]
Suh, D.H.; Kim, M.A.; Kim, H.; Kim, M.K.; Kim, H.S.; Chung, H.H.; Kim, Y.B.; Song, Y.S. Association of overexpression of hexokinase II with chemoresistance in epithelial ovarian cancer. Clin. Exp. Med., 2014, 14, 345-353.
[http://dx.doi.org/10.1007/s10238-013-0250-9] [PMID: 23949336]
[136]
Calmettes, G.; Ribalet, B.; John, S.; Korge, P.; Ping, P.; Weiss, J.N. Hexokinases and cardioprotection. J. Mol. Cell. Cardiol., 2015, 78, 107-115.
[http://dx.doi.org/10.1016/j.yjmcc.2014.09.020] [PMID: 25264175]
[137]
Nederlof, R.; Eerbeek, O.; Hollmann, M.W.; Southworth, R.; Zuurbier, C.J. Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart. Br. J. Pharmacol., 2014, 171(8), 2067-2079.
[http://dx.doi.org/10.1111/bph.12363] [PMID: 24032601]
[138]
Peng, Q.; Zhou, Q.; Zhou, J.; Zhong, D.; Pan, F.; Liang, H. Stable RNA interference of hexokinase II gene inhibits human colon cancer LoVo cell growth in vitro and in vivo. Cancer Biol. Ther., 2008, 7(7), 1128-1135.
[http://dx.doi.org/10.4161/cbt.7.7.6199] [PMID: 18535403]
[139]
McWilliam, H.; Li, W.; Uludag, M.; Squizzato, S.; Park, Y.M.; Buso, N.; Cowley, A.P.; Lopez, R. Analysis tool web services from the EMBL-EBI. Nucleic Acids Res, 2013, 41(Web Server issue), W597-600.
[http://dx.doi.org/10.1093/nar/gkt376] [PMID: 23671338]
[140]
Tsai, H.J. Functional organization and evolution of mammalian hexokinases: mutations that caused the loss of catalytic activity in N-terminal halves of type I and type III isozymes. Arch. Biochem. Biophys., 1999, 369(1), 149-156.
[http://dx.doi.org/10.1006/abbi.1999.1326] [PMID: 10462451]
[141]
Nawaz, M.H.; Ferreira, J.C.; Nedyalkova, L.; Zhu, H.; Carrasco-López, C.; Kirmizialtin, S.; Rabeh, W.M. The catalytic inactivation of the N-half of human hexokinase 2 and structural and biochemical characterization of its mitochondrial conformation. Biosci. Rep., 2018, 38(1)BSR20171666
[http://dx.doi.org/10.1042/BSR20171666] [PMID: 29298880]
[142]
Aleshin, A.E.; Kirby, C.; Liu, X.; Bourenkov, G.P.; Bartunik, H.D.; Fromm, H.J.; Honzatko, R.B. Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation. J. Mol. Biol., 2000, 296(4), 1001-1015.
[http://dx.doi.org/10.1006/jmbi.1999.3494] [PMID: 10686099]
[143]
Aleshin, A.E.; Zeng, C.; Bourenkov, G.P.; Bartunik, H.D.; Fromm, H.J.; Honzatko, R.B. The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate. Structure, 1998, 6(1), 39-50.
[http://dx.doi.org/10.1016/S0969-2126(98)00006-9] [PMID: 9493266]
[144]
Shen, L.; Gao, Y.; Honzatko, R. B. Inhibitor sites of unequal affinity linked by binding synergism in mutant forms of recombinant human hexokinase type-I. RSCB PDB - 4F9O, Released, 2013, 12 June.
[145]
Scatena, R.; Bottoni, P.; Pontoglio, A.; Mastrototaro, L.; Giardina, B. Glycolytic enzyme inhibitors in cancer treatment. Expert Opin. Investig. Drugs, 2008, 17(10), 1533-1545.
[http://dx.doi.org/10.1517/13543784.17.10.1533] [PMID: 18808312]
[146]
Lis, P.; Dyląg, M.; Niedźwiecka, K.; Ko, Y.H.; Pedersen, P.L.; Goffeau, A.; Ułaszewski, S. The HK2 dependent “warburg effect” and mitochondrial oxidative phosphorylation in cancer: Targets for effective therapy with 3-bromopyruvate. Molecules, 2016, 21(12)e1730
[http://dx.doi.org/10.3390/molecules21121730] [PMID: 27983708]
[147]
Nath, K.; Guo, L.; Nancolas, B.; Nelson, D.S.; Shestov, A.A.; Lee, S.C.; Roman, J.; Zhou, R.; Leeper, D.B.; Halestrap, A.P.; Blair, I.A.; Glickson, J.D. Mechanism of antineoplastic activity of lonidamine. Biochim. Biophys. Acta, 2016, 1866(2), 151-162.
[http://dx.doi.org/10.1016/j.bbcan.2016.08.001] [PMID: 27497601]
[148]
Sheng, H.; Tang, W. Glycolysis inhibitors for anticancer therapy: a review of recent patents. Recent Patents Anticancer Drug Discov., 2016, 11(3), 297-308.
[http://dx.doi.org/10.2174/1574892811666160415160104] [PMID: 27087655]
[149]
Pelicano, H.; Martin, D.S.; Xu, R.H.; Huang, P. Glycolysis inhibition for anticancer treatment. Oncogene, 2006, 25(34), 4633-4646.
[http://dx.doi.org/10.1038/sj.onc.1209597] [PMID: 16892078]
[150]
Ko, Y. H. Compositions and methods for the treatment of cancer. US8324175B2, 2012.
[151]
Ricci, J.-E. Glycolytic inhibitor with cytotoxic agent for use in the treatment of a cancer. WO2012123774A1, 2012.
[152]
Priebe, W.; Conrad, C.; Madden, T.; Fokt, I.; Szymanski, S.; Antonovic, L. Inhibitors of glycolysis useful in the treatment of brain tumors. WO2009108926, 2009.
[153]
Mjalli, A.M.M.; Gaddam, B.; Gohimukkula, D.R.; Polisetti, D.R.; Rao, M.; Guzel, M.; Singh, N. HAJJO, R.; Andrews, R.C.; Xie, R.; Kalpathy, S.; SAHOO, S.P.; Davis, S.T. WO2016196890A1, 2016.
[154]
Palazzo, G.; Silvestrini, B. Substituted 1-benzyl-1Hindazole- 3-carboxylic acids and derivatives tereof. US3895026A, 1975.
[155]
Tidmarsh, G.; Selick, H. Treatment of Benign Prostatic Hyperplasia Using Energolytic Agents. US20060172953A1, 2006.
[156]
Tidmarsh, G. Prevention of Cancer. WO2006010073A1, 2006.
[157]
Matteucci, M.; Rao, P.; Duan, J.-X. Lonidamine Analogs. US20070043057A1, 2007.
[158]
Geschwind, J.-F.; Vali, M. Methods and compositions of 3- halopyruvate and related compounds for the treatment of cancer. US20100137434A1, 2010.
[159]
Ko, Y. H. Composition and method for the efficacious and safe administration of halopyruvate for the treatment of cancer. US7754693B2, 2010.
[160]
Ko, Y. H. Compositions and methods for the treatment of cancer. US20110008418A1, 2011.
[161]
Dhar, S.; Marrache, S. Mitochondrial delivery of 3- bromopyruvate. WO2015138992A1, 2015.
[162]
Ko, Y. H. Compositions and methods for the treatment of cancer. US20130157925A1, 2013.
[163]
Ko, Y. H. Compositions and methods for the treatment of cancer. US9149449B2, 2015.
[164]
Ko, Y. H. Compositions and methods for the treatment of cancer. US9849103B2, 2017.
[165]
Ko, Y. H.; Geschwind, J.-F.; Pedersen, P. Therapeutics for cancer using 3-bromopyruvate and other selective inhibitors of ATP production. US20030087961A1, 2003.
[166]
Ko, Y. H.; Geschwind, J.-F. H.; Pedersen, P. L. Therapeutics for cancer using 3-bromopyruvate and other selective inhibitors of ATP production US20090326068A1, 2009.
[167]
Geschwind, J.-F.; Vali, M. Therapeutics for cancer using 3- bromopyruvate and other selective inhibitors of ATP production. US20100203110A1, 2010.
[168]
Geschwind, J.-F.; Vali, M. Methods of treatment using 3- bromopyruvate and other selective inhibitors of ATP production. US20130046019A1, 2013.
[169]
Tidmarsh, G. Treatment of cancer with 2-Deoxyglucose. WO2004062604A2, 2004.
[170]
Lampidis, T. J.; Priebe, W. Cancer chemotherapy with 2- Deoxy-D-Glucose. US6670330B1, 2003.
[171]
Yao, J.; Brinton, R. D. Cancer chemotherapy with 2-Deoxy- D-Glucose. US6670330B1, 2012.
[172]
Tidmarsh, G.; Ammons, S. Treating metabolic syndrome with 2-Deoxy-D-Glucose. WO2007044679A2, 2007.
[173]
Priebe, W.; Cybulski, M.; Fokt, I.; Skora, S.; Conrad, C.; Madden, T. Esters of 2-Deoxy-Monosacharides with antiproliferative activity. US20160184336A1, 2016.
[174]
Lampidis, T. J.; Kurtoglu, M.; Liu, H. Combination therapy with fenofibrate and 2-deoxyglucose or 2-deoxymannose. WO201665353A1, 2016.
[175]
Laudau, B. R. Treatment of cancer with 2-Deoxygalactose. CA2655614, 2007.
[176]
Laszlo, J.; Humphreys, S.R.; Goldin, A. Effects of glucose analogues (2-deoxy-D-glucose, 2-deoxy-D-galactose) on experimental tumors. J. Natl. Cancer Inst., 1960, 24(2), 267-281.
[PMID: 14414406]
[177]
Barban, S.; Schulze, H.O. The effects of 2-deoxyglucose on the growth and metabolism of cultured human cells. J. Biol. Chem., 1961, 236(7), 1887-1890.
[PMID: 13686731]
[178]
Arbe, M.F.; Fondello, C.; Agnetti, L.; Álvarez, G.M.; Tellado, M.N.; Glikin, G.C.; Finocchiaro, L.M.E.; Villaverde, M.S. Inhibition of bioenergetic metabolism by the combination of metformin and 2-deoxyglucose highly decreases viability of feline mammary carcinoma cells. Res. Vet. Sci., 2017, 114, 461-468.
[http://dx.doi.org/10.1016/j.rvsc.2017.07.035] [PMID: 28802138]
[179]
Kurtoglu, M.; Maher, J.C.; Lampidis, T.J. Differential toxic mechanisms of 2-deoxy-D-glucose versus 2-fluorodeoxy-D-glucose in hypoxic and normoxic tumor cells. Antioxid. Redox Signal., 2007, 9(9), 1383-1390.
[http://dx.doi.org/10.1089/ars.2007.1714] [PMID: 17627467]
[180]
Tidmarsh, G. Treatment of Cancer with 2-Deoxyglucose. US6979675B2, 2005.
[181]
Baron, J.C.; Lebrun-Grandie, P.; Collard, P.; Crouzel, C.; Mestelan, G.; Bousser, M.G. Noninvasive measurement of blood flow, oxygen consumption, and glucose utilization in the same brain regions in man by positron emission tomography: concise communication. J. Nucl. Med., 1982, 23(5), 391-399.
[PMID: 6978932]
[182]
Wilson, J.E.; Chung, V. Rat brain hexokinase: further studies on the specificity of the hexose and hexose 6-phosphate binding sites. Arch. Biochem. Biophys., 1989, 269(2), 517-525.
[http://dx.doi.org/10.1016/0003-9861(89)90135-5] [PMID: 2919881]
[183]
Grün, B.R.; Berger, U.; Oberdorfer, F.; Hull, W.E.; Ostertag, H.; Friedrich, E.; Lehmann, J.; Keppler, D. Metabolism and actions of 2-deoxy-2-fluoro-D-galactose in vivo. Eur. J. Biochem., 1990, 190(1), 11-19.
[http://dx.doi.org/10.1111/j.1432-1033.1990.tb15539.x] [PMID: 2114284]
[184]
Courtois, P.; Sener, A.; Malaisse, W.J. D-mannoheptulose phosphorylation by hexokinase isoenzymes. Int. J. Mol. Med., 2001, 7(4), 359-363.
[PMID: 11254873]
[185]
Coore, H.G.; Randle, P.J. Inhibition of glucose phosphorylation by mannoheptulose. Biochem. J., 1964, 91(1), 56-59.
[PMID: 5319361]
[186]
Scruel, O.; Vanhoutte, C.; Sener, A.; Malaisse, W.J. Interference of D-mannoheptulose with D-glucose phosphorylation, metabolism and functional effects: comparison between liver, parotid cells and pancreatic islets. Mol. Cell. Biochem., 1998, 187(1-2), 113-120.
[http://dx.doi.org/10.1023/A:1006812300200] [PMID: 9788748]
[187]
Picton, S.; Malaisse, W.J. Environmental modulation of the inhibitory action of D-mannoheptulose upon D-glucose metabolism in isolated rat pancreatic islets. Cell Biochem. Funct., 1999, 17(1), 65-71.
[http://dx.doi.org/10.1002/(SICI)1099-0844(199903)17:1<65:AID-CBF812>3.0.CO;2-T] [PMID: 10191510]
[188]
Malaisse, W.J.; Kadiata, M.M.; Scruel, O.; Sener, A. Esterification of D-mannoheptulose confers to the heptose inhibitory action on D-glucose metabolism in parotid cells. Biochem. Mol. Biol. Int., 1998, 44(3), 625-633.
[http://dx.doi.org/10.1080/15216549800201662] [PMID: 9556224]
[189]
Papaldo, P.; Lopez, M.; Cortesi, E.; Cammilluzzi, E.; Antimi, M.; Terzoli, E.; Lepidini, G.; Vici, P.; Barone, C.; Ferretti, G.; Di Cosimo, S.; Nisticò, C.; Carlini, P.; Conti, F.; Di Lauro, L.; Botti, C.; Vitucci, C.; Fabi, A.; Giannarelli, D.; Marolla, P. Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide. J. Clin. Oncol., 2003, 21(18), 3462-3468.
[http://dx.doi.org/10.1200/JCO.2003.03.034] [PMID: 12972521]
[190]
Guo, L.; Shestov, A.A.; Worth, A.J.; Nath, K.; Nelson, D.S.; Leeper, D.B.; Glickson, J.D.; Blair, I.A. Inhibition of mitochondrial complex II by the anticancer agent lonidamine. J. Biol. Chem., 2016, 291(1), 42-57.
[http://dx.doi.org/10.1074/jbc.M115.697516] [PMID: 26521302]
[191]
Nath, K.; Nelson, D.S.; Roman, J.; Putt, M.E.; Lee, S.C.; Leeper, D.B.; Glickson, J.D. Effect of lonidamine on systemic therapy of DB-1 human melanoma xenografts with Temozolomide. Anticancer Res., 2017, 37(7), 3413-3421.
[http://dx.doi.org/10.21873/anticanres.11708] [PMID: 28668829]
[192]
Ko, Y.H.; Pedersen, P.L.; Geschwind, J.F. Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer Lett., 2001, 173(1), 83-91.
[http://dx.doi.org/10.1016/S0304-3835(01)00667-X] [PMID: 11578813]
[193]
Huang, P.; Keating, M. J.; Xu, R. Propyl 3-bromo-2-oxopropionate and derivatives as novel anticancer agents. US20060058383A1, 2006.
[194]
Ihrlund, L.S.; Hernlund, E.; Khan, O.; Shoshan, M.C. 3-Bromopyruvate as inhibitor of tumour cell energy metabolism and chemopotentiator of platinum drugs. Mol. Oncol., 2008, 2(1), 94-101.
[http://dx.doi.org/10.1016/j.molonc.2008.01.003] [PMID: 19383331]
[195]
Ko, Y.H.; Smith, B.L.; Wang, Y.; Pomper, M.G.; Rini, D.A.; Torbenson, M.S.; Hullihen, J.; Pedersen, P.L. Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem. Biophys. Res. Commun., 2004, 324(1), 269-275.
[http://dx.doi.org/10.1016/j.bbrc.2004.09.047] [PMID: 15465013]
[196]
Calviño, E.; Estañ, M.C.; Sánchez-Martín, C.; Brea, R.; de Blas, E. Boyano-Adánez, Mdel.C.; Rial, E.; Aller, P. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation. J. Pharmacol. Exp. Ther., 2014, 348(2), 324-335.
[http://dx.doi.org/10.1124/jpet.113.206714] [PMID: 24307199]
[197]
Wicks, R.T.; Azadi, J.; Mangraviti, A.; Zhang, I.; Hwang, L.; Joshi, A.; Bow, H.; Hutt-Cabezas, M.; Martin, K.L.; Rudek, M.A.; Zhao, M.; Brem, H.; Tyler, B.M. Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma. Neuro-oncol., 2015, 17(1), 70-80.
[http://dx.doi.org/10.1093/neuonc/nou143] [PMID: 25053853]
[198]
Hanafy, N.A.; Dini, L.; Citti, C.; Cannazza, G.; Leporatti, S. Inihibition of glycolysis by using a micro/nano-lipid bromopyruvic chitosan carrier as a promising tool to improve treatment of hepatocellular carcinoma. Nanomaterials (Basel), 2018, 8(1)e34
[http://dx.doi.org/10.3390/nano8010034] [PMID: 29320411]
[199]
Gandham, S.K.; Talekar, M.; Singh, A.; Amiji, M.M. Inhibition of hexokinase-2 with targeted liposomal 3-bromopyruvate in an ovarian tumor spheroid model of aerobic glycolysis. Int. J. Nanomedicine, 2015, 10, 4405-4423.
[200]
Feldwisch-Drentrup, H. Candidate cancer drug suspected after death of three patients at an alternative medicine clinic. Science, 2016.
[http://dx.doi.org/10.1126/science.aah7192]
[201]
Business Wire. PreScience Labs Announced that the FDA Accepts IND Application for Novel Oncology Drug., 2013. Available at: https://www.businesswire.com/news/home/20130724006023/en/PreScience-Labs-Announced-FDA-Accepts-IND-Application
[202]
Salani, B.; Marini, C.; Rio, A.D.; Ravera, S.; Massollo, M.; Orengo, A.M.; Amaro, A.; Passalacqua, M.; Maffioli, S.; Pfeffer, U.; Cordera, R.; Maggi, D.; Sambuceti, G. Metformin impairs glucose consumption and survival in Calu-1 cells by direct inhibition of hexokinase-II. Sci. Rep., 2013, 3, 2070.
[http://dx.doi.org/10.1038/srep02070] [PMID: 23797762]
[203]
Marini, C.; Salani, B.; Massollo, M.; Amaro, A.; Esposito, A.I.; Orengo, A.M.; Capitanio, S.; Emionite, L.; Riondato, M.; Bottoni, G.; Massara, C.; Boccardo, S.; Fabbi, M.; Campi, C.; Ravera, S.; Angelini, G.; Morbelli, S.; Cilli, M.; Cordera, R.; Truini, M.; Maggi, D.; Pfeffer, U.; Sambuceti, G. Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer. Cell Cycle, 2013, 12(22), 3490-3499.
[http://dx.doi.org/10.4161/cc.26461] [PMID: 24240433]
[204]
Kang, Y.T.; Hsu, W.C.; Wu, C.H.; Hsin, I.L.; Wu, P.R.; Yeh, K.T.; Ko, J.L. Metformin alleviates nickel-induced autophagy and apoptosis via inhibition of hexokinase-2, activating lipocalin-2, in human bronchial epithelial cells. Oncotarget, 2017, 8(62), 105536-105552.
[http://dx.doi.org/10.18632/oncotarget.22317] [PMID: 29285270]
[205]
Pernicova, I.; Korbonits, M. Metformin--mode of action and clinical implications for diabetes and cancer. Nat. Rev. Endocrinol., 2014, 10(3), 143-156.
[http://dx.doi.org/10.1038/nrendo.2013.256] [PMID: 24393785]
[206]
US National Library of Medicine- clinicaltrials.gov Available at: ClinicalTrials.gov (Accessed Date: 28 Feb, 2018)
[207]
Maley, F.; Lardy, H.A. Synthesis of N-substituted glucosamines and their effect on hexokinase. J. Biol. Chem., 1955, 214(2), 765-773.
[PMID: 14381414]
[208]
Coats, E.A.; Skau, K.A.; Caperelli, C.A.; Solomacha, D. Exploring the hexokinase glucose binding site through correlation analysis and molecular modeling of glucosamine inhibitors. J. Enzyme Inhib., 1992, 6(4), 271-282.
[http://dx.doi.org/10.3109/14756369309020177] [PMID: 1284964]
[209]
Li, W.; Zheng, M.; Wu, S.; Gao, S.; Yang, M.; Li, Z.; Min, Q.; Sun, W.; Chen, L.; Xiang, G.; Li, H. Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2. J. Exp. Clin. Cancer Res., 2017, 36(1), 58.
[http://dx.doi.org/10.1186/s13046-017-0530-4] [PMID: 28427443]
[210]
Bao, F.; Yang, K.; Wu, C.; Gao, S.; Wang, P.; Chen, L.; Li, H. New natural inhibitors of hexokinase 2 (HK2): Steroids from Ganoderma sinense. Fitoterapia, 2018, 125, 123-129.
[http://dx.doi.org/10.1016/j.fitote.2018.01.001] [PMID: 29305912]
[211]
Flaherty, D.P.; Harris, M.T.; Schroeder, C.E.; Khan, H.; Kahney, E.W.; Hackler, A.L.; Patrick, S.L.; Weiner, W.S.; Aubé, J.; Sharlow, E.R.; Morris, J.C.; Golden, J.E. Optimization and evaluation of antiparasitic benzamidobenzoic acids as inhibitors of kinetoplastid hexokinase 1. ChemMedChem, 2017, 12(23), 1994-2005.
[http://dx.doi.org/10.1002/cmdc.201700592] [PMID: 29105342]
[212]
Sharlow, E.R.; Lyda, T.A.; Dodson, H.C.; Mustata, G.; Morris, M.T.; Leimgruber, S.S.; Lee, K.H.; Kashiwada, Y.; Close, D.; Lazo, J.S.; Morris, J.C. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity. PLoS Negl. Trop. Dis., 2010, 4(4)e659
[http://dx.doi.org/10.1371/journal.pntd.0000659] [PMID: 20405000]
[213]
Gordhan, H.M.; Patrick, S.L.; Swasy, M.I.; Hackler, A.L.; Anayee, M.; Golden, J.E.; Morris, J.C.; Whitehead, D.C. Evaluation of substituted ebselen derivatives as potential trypanocidal agents. Bioorg. Med. Chem. Lett., 2017, 27(3), 537-541.
[http://dx.doi.org/10.1016/j.bmcl.2016.12.021] [PMID: 28043795]
[214]
Sharlow, E.; Golden, J.E.; Dodson, H.; Morris, M.; Hesser, M.; Lyda, T.; Leimgruber, S.; Shroeder, C.E.; Flaherty, D.P.; Weiner, W.S.; Simpson, D.; Lazo, J.S.; Aubé, J.; al Morris, J.C. Identification of inhibitors of Trypanosoma brucei hexokinases. Probe Reports from the NIH Molecular Libraries Program [Internet],, 2011. Available at: https://www.ncbi.nlm.nih.gov/books/NBK63599/ (Accessed Date: 28 Feb, 2018)
[PMID: 21961120]
[215]
Gordhan, H.M.; Milanes, J.E.; Qiu, Y.; Golden, J.E.; Christensen, K.A.; Morris, J.C.; Whitehead, D.C. A targeted delivery strategy for the development of potent trypanocides. Chem. Commun. (Camb.), 2017, 53(62), 8735-8738.
[http://dx.doi.org/10.1039/C7CC03378H] [PMID: 28726862]
[216]
Saucedo-Mendiola, M.L.; Salas-Pacheco, J.M.; Nájera, H.; Rojo-Domínguez, A.; Yépez-Mulia, L.; Avitia-Domínguez, C.; Téllez-Valencia, A. Discovery of Entamoeba histolytica hexokinase 1 inhibitors through homology modeling and virtual screening. J. Enzyme Inhib. Med. Chem., 2014, 29(3), 325-332.
[http://dx.doi.org/10.3109/14756366.2013.779265] [PMID: 23534932]
[217]
Tielens, A.G.M.; Houweling, M.; Van den Bergh, S.G. The effect of 5-thioglucose on the energy metabolism of Schistosoma mansoni in vitro. Biochem. Pharmacol., 1985, 34(18), 3369-3373.
[http://dx.doi.org/10.1016/0006-2952(85)90359-4] [PMID: 4038343]
[218]
Willson, M.; Alric, I.; Perie, J.; Sanejouand, Y.H. Yeast hexokinase inhibitors designed from the 3-D enzyme structure rebuilding. J. Enzyme Inhib., 1997, 12(2), 101-121.
[http://dx.doi.org/10.3109/14756369709035812] [PMID: 9247853]
[219]
Chambers, J.W.; Fowler, M.L.; Morris, M.T.; Morris, J.C. The anti-trypanosomal agent lonidamine inhibits Trypanosoma brucei hexokinase 1. Mol. Biochem. Parasitol., 2008, 158(2), 202-207.
[http://dx.doi.org/10.1016/j.molbiopara.2007.12.013] [PMID: 18262292]
[220]
Goldin, N.; Arzoine, L.; Heyfets, A.; Israelson, A.; Zaslavsky, Z.; Bravman, T.; Bronner, V.; Notcovich, A.; Shoshan-Barmatz, V.; Flescher, E. Methyl jasmonate binds to and detaches mitochondria-bound hexokinase. Oncogene, 2008, 27(34), 4636-4643.
[http://dx.doi.org/10.1038/onc.2008.108] [PMID: 18408762]
[221]
Raviv, Z.; Cohen, S.; Reischer-Pelech, D. The anti-cancer activities of jasmonates. Cancer Chemother. Pharmacol., 2013, 71(2), 275-285.
[http://dx.doi.org/10.1007/s00280-012-2039-z] [PMID: 23196641]
[222]
Arzoine, L.; Zilberberg, N.; Ben-Romano, R.; Shoshan-Barmatz, V. Voltage-dependent anion channel 1-based peptides interact with hexokinase to prevent its anti-apoptotic activity. J. Biol. Chem., 2009, 284(6), 3946-3955.
[http://dx.doi.org/10.1074/jbc.M803614200] [PMID: 19049977]
[223]
Prezma, T.; Shteinfer, A.; Admoni, L.; Raviv, Z.; Sela, I.; Levi, I.; Shoshan-Barmatz, V. VDAC1-based peptides: novel pro-apoptotic agents and potential therapeutics for Bcell chronic lymphocytic leukemia. Cell Death Dis, 2013, 4e809
[224]
Woldetsadik, A.D.; Vogel, M.C.; Rabeh, W.M.; Magzoub, M. Hexokinase II-derived cell-penetrating peptide targets mitochondria and triggers apoptosis in cancer cells. FASEB J., 2017, 31(5), 2168-2184.
[http://dx.doi.org/10.1096/fj.201601173R] [PMID: 28183803]
[225]
Hauser, D.N.; Mamais, A.; Conti, M.M.; Primiani, C.T.; Kumaran, R.; Dillman, A.A.; Langston, R.G.; Beilina, A.; Garcia, J.H.; Diaz-Ruiz, A.; Bernier, M.; Fiesel, F.C.; Hou, X.; Springer, W.; Li, Y.; de Cabo, R.; Cookson, M.R. Hexokinases link DJ-1 to the PINK1/parkin pathway. Mol. Neurodegener., 2017, 12(1), 70.
[http://dx.doi.org/10.1186/s13024-017-0212-x] [PMID: 28962651]
[226]
Varanasi, S.K.; Jaggi, U.; Hay, N.; Rouse, B.T. Hexokinase II may be dispensable for CD4 T cell responses against a virus infection. PLoS One, 2018, 13(1)e0191533
[http://dx.doi.org/10.1371/journal.pone.0191533] [PMID: 29352298]
[227]
Wang, C.; Silverman, R.M.; Shen, J.; O’Keefe, R.J. Distinct metabolic programs induced by TGF-β1 and BMP2 in human articular chondrocytes with osteoarthritis. J. Orthop. Translat., 2018, 12, 66-73.
[http://dx.doi.org/10.1016/j.jot.2017.12.004] [PMID: 29662780]
[228]
Li, Y.; Lu, B.; Sheng, L.; Zhu, Z.; Sun, H.; Zhou, Y.; Yang, Y.; Xue, D.; Chen, W.; Tian, X.; Du, Y.; Yan, M.; Zhu, W.; Xing, F.; Li, K.; Lin, S.; Qiu, P.; Su, X.; Huang, Y.; Yan, G.; Yin, W. Hexokinase 2-dependent hyperglycolysis driving microglial activation contributes to ischemic brain injury. J. Neurochem., 2018, 144(2), 186-200.
[http://dx.doi.org/10.1111/jnc.14267] [PMID: 29205357]
[229]
Bensaad, K.; Tsuruta, A.; Selak, M.A.; Vidal, M.N.C.; Nakano, K.; Bartrons, R.; Gottlieb, E.; Vousden, K.H. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell, 2006, 126(1), 107-120.
[http://dx.doi.org/10.1016/j.cell.2006.05.036] [PMID: 16839880]
[230]
Cheung, E.C.; Ludwig, R.L.; Vousden, K.H. Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proc. Natl. Acad. Sci. USA, 2012, 109(50), 20491-20496.
[http://dx.doi.org/10.1073/pnas.1206530109] [PMID: 23185017]
[231]
Robles López, K.L. The role of TIGAR in Parkinson’s disease, 2017. Available at: http://etheses.whiterose.ac.uk/id/eprint/18939(Accessed Date: 13 March,2018)
[232]
Okatsu, K.; Iemura, S.; Koyano, F.; Go, E.; Kimura, M.; Natsume, T.; Tanaka, K.; Matsuda, N. Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase. Biochem. Biophys. Res. Commun., 2012, 428(1), 197-202.
[http://dx.doi.org/10.1016/j.bbrc.2012.10.041] [PMID: 23068103]
[233]
McCoy, M.K.; Kaganovich, A.; Rudenko, I.N.; Ding, J.; Cookson, M.R. Hexokinase activity is required for recruitment of parkin to depolarized mitochondria. Hum. Mol. Genet., 2014, 23(1), 145-156.
[http://dx.doi.org/10.1093/hmg/ddt407] [PMID: 23962723]
[234]
Ghosh, S.; Gupta, P.; Sen, E. TNFα driven HIF-1α-hexokinase II axis regulates MHC-I cluster stability through actin cytoskeleton. Exp. Cell Res., 2016, 340(1), 116-124.
[http://dx.doi.org/10.1016/j.yexcr.2015.11.016] [PMID: 26597758]
[235]
Wolf, A.J.; Reyes, C.N.; Liang, W.; Becker, C.; Shimada, K.; Wheeler, M.L.; Cho, H.C.; Popescu, N.I.; Coggeshall, K.M.; Arditi, M.; Underhill, D.M. Hexokinase is an innate immune receptor for the detection of bacterial peptidoglycan. Cell, 2016, 166(3), 624-636.
[http://dx.doi.org/10.1016/j.cell.2016.05.076] [PMID: 27374331]
[236]
Okuyama, N.; Matsuda, S.; Yamashita, A.; Moriguchi-Goto, S.; Sameshima, N.; Iwakiri, T.; Matsuura, Y.; Sato, Y.; Asada, Y. Human coronary thrombus formation is associated with degree of plaque disruption and expression of tissue factor and hexokinase II. Circ. J., 2015, 79(11), 2430-2438.
[http://dx.doi.org/10.1253/circj.CJ-15-0394] [PMID: 26346032]
[237]
Barrero, C.A.; Datta, P.K.; Sen, S.; Deshmane, S.; Amini, S.; Khalili, K.; Merali, S. HIV-1 Vpr modulates macrophage metabolic pathways: a SILAC-based quantitative analysis. PLoS One, 2013, 8(7)e68376
[http://dx.doi.org/10.1371/journal.pone.0068376] [PMID: 23874603]
[238]
Xu, J.; Lin, S.; Myers, R.W.; Addona, G.; Berger, J.P.; Campbell, B.; Chen, H.S.; Chen, Z.; Eiermann, G.J.; Elowe, N.H.; Farrer, B.T.; Feng, W.; Fu, Q.; Kats-Kagan, R.; Kavana, M.; Malkani, S.; McMasters, D.R.; Mitra, K.; Pachanski, M.J.; Tong, X.; Trujillo, M.E.; Xu, L.; Zhang, B.; Zhang, F.; Zhang, R.; Parmee, E.R. Novel, highly potent systemic glucokinase activators for the treatment of Type 2 Diabetes Mellitus. Bioorg. Med. Chem. Lett., 2017, 27(9), 2069-2073.
[http://dx.doi.org/10.1016/j.bmcl.2016.10.085] [PMID: 28284804]
[239]
Malkki, M.; Laakso, M.; Deeb, S.S. The human hexokinase II gene promoter: functional characterization and detection of variants among patients with NIDDM. Diabetologia, 1997, 40(12), 1461-1469.
[http://dx.doi.org/10.1007/s001250050850] [PMID: 9447955]
[240]
Courteau, L.; Crasto, J.; Hassanzadeh, G.; Baird, S.D.; Hodgins, J.; Liwak-Muir, U.; Fung, G.; Luo, H.; Stojdl, D.F.; Screaton, R.A.; Holcik, M. Hexokinase 2 controls cellular stress response through localization of an RNA-binding protein. Cell Death Dis., 2015, 6e1837
[http://dx.doi.org/10.1038/cddis.2015.209] [PMID: 26247723]
[241]
Sheikh, T.; Gupta, P.; Gowda, P.; Patrick, S.; Sen, E. Hexokinase 2 and nuclear factor erythroid 2-related factor 2 transcriptionally coactivate xanthine oxidoreductase expression in stressed glioma cells. J. Biol. Chem., 2018, 293(13), 4767-4777.
[http://dx.doi.org/10.1074/jbc.M117.816785] [PMID: 29414774]
[242]
van Montfort, R.L.M.; Workman, P. Structure-based drug design: aiming for a perfect fit. Essays Biochem., 2017, 61(5), 431-437.
[http://dx.doi.org/10.1042/EBC20170052] [PMID: 29118091]
[243]
Stewart, B.W.; Wild, C.P. World Cancer Report; International agency for research on cancer: Lyon, France, 2014.
[244]
Mendoza, R.L. The 21st Century Cures Act: pharmacoeconomic boon or bane? J. Med. Econ., 2017, 20(4), 315-317.
[http://dx.doi.org/10.1080/13696998.2017.1282865] [PMID: 28092219]
[245]
Kleczkowska, P.; Kowalczyk, A.; Lesniak, A.; Bujalska-Zadrozny, M. The discovery and development of drug combinations for the treatment of various diseases from patent literature (1980-Present). Curr. Top. Med. Chem., 2017, 17(8), 875-894.
[http://dx.doi.org/10.2174/1568026616666160818152257] [PMID: 27538458]
[246]
Tannock, I.F.; Hickman, J.A. Limits to personalized cancer medicine. N. Engl. J. Med., 2016, 375(13), 1289-1294.
[http://dx.doi.org/10.1056/NEJMsb1607705] [PMID: 27682039]
[247]
Holohan, C.; Van Schaeybroeck, S.; Longley, D.B.; Johnston, P.G. Cancer drug resistance: an evolving paradigm. Nat. Rev. Cancer, 2013, 13(10), 714-726.
[http://dx.doi.org/10.1038/nrc3599] [PMID: 24060863]
[248]
Cairns, R.A.; Mak, T.W. The current state of cancer metabolism. Nat. Rev. Cancer, 2016, 16(10), 613-614.
[http://dx.doi.org/10.1038/nrc.2016.100]
[249]
Mathupala, S.P.; Ko, Y.H.; Pedersen, P.L. Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene, 2006, 25(34), 4777-4786.
[http://dx.doi.org/10.1038/sj.onc.1209603] [PMID: 16892090]
[250]
Naldini, L. Gene therapy returns to centre stage. Nature, 2015, 526(7573), 351-360.
[http://dx.doi.org/10.1038/nature15818] [PMID: 26469046]
[251]
Cox, D.B.T.; Platt, R.J.; Zhang, F. Therapeutic genome editing: prospects and challenges. Nat. Med., 2015, 21(2), 121-131.
[http://dx.doi.org/10.1038/nm.3793] [PMID: 25654603]
[252]
Ibraheem, D.; Elaissari, A.; Fessi, H. Gene therapy and DNA delivery systems. Int. J. Pharm., 2014, 459(1-2), 70-83.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.041] [PMID: 24286924]

Rights & Permissions Print Cite
Article Metrics
156
23
1
2
© 2024 Bentham Science Publishers | Privacy Policy