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http://dx.doi.org/10.5487/TR.2016.32.3.177

Targeting Cancer Metabolism - Revisiting the Warburg Effects  

Tran, Quangdon (Department of Pharmacology and Medical Science, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University)
Lee, Hyunji (Department of Pharmacology and Medical Science, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University)
Park, Jisoo (Department of Pharmacology and Medical Science, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University)
Kim, Seon-Hwan (Department of Neurosurgery, Institute for Cancer Research, College of Medicine, Chungnam National University)
Park, Jongsun (Department of Pharmacology and Medical Science, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University)
Publication Information
Toxicological Research / v.32, no.3, 2016 , pp. 177-193 More about this Journal
Abstract
After more than half of century since the Warburg effect was described, this atypical metabolism has been standing true for almost every type of cancer, exhibiting higher glycolysis and lactate metabolism and defective mitochondrial ATP production. This phenomenon had attracted many scientists to the problem of elucidating the mechanism of, and reason for, this effect. Several models based on oncogenic studies have been proposed, such as the accumulation of mitochondrial gene mutations, the switch from oxidative phosphorylation respiration to glycolysis, the enhancement of lactate metabolism, and the alteration of glycolytic genes. Whether the Warburg phenomenon is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. Moreover, the exact reasons and physiological values of this peculiar metabolism in cancer remain unclear. Although there are some pharmacological compounds, such as 2-deoxy-D-glucose, dichloroacetic acid, and 3-bromopyruvate, therapeutic strategies, including diet, have been developed based on targeting the Warburg effect. In this review, we will revisit the Warburg effect to determine how much scientists currently understand about this phenomenon and how we can treat the cancer based on targeting metabolism.
Keywords
Energy metabolism; Warburg effects; Cancer metabolism; Mitochondria;
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1 Zhou, Z.H., McCarthy, D.B., O'Connor, C.M., Reed, L.J. and Stoops, J.K. (2001) The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes. Proc. Natl. Acad. Sci. U.S.A., 98, 14802-14807.   DOI
2 Smolle, M., Prior, A.E., Brown, A.E., Cooper, A., Byron, O. and Lindsay, J.G. (2006) A new level of architectural complexity in the human pyruvate dehydrogenase complex. J. Biol. Chem., 281, 19772-19780.   DOI
3 Brautigam, C.A., Wynn, R.M., Chuang, J.L., Machius, M., Tomchick, D.R. and Chuang, D.T. (2006) Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. Structure, 14, 611-621.1   DOI
4 Bowker-Kinley, M.M., Davis, W.I., Wu, P., Harris, R.A. and Popov, K.M. (1998) Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochem. J., 329, 191-196.   DOI
5 Huang, B., Wu, P., Popov, K.M. and Harris, R.A. (2003) Starvation and diabetes reduce the amount of pyruvate dehydrogenase phosphatase in rat heart and kidney. Diabetes, 52, 1371-1376.   DOI
6 Motojima, K. and Seto, K. (2003) Fibrates and statins rapidly and synergistically induce pyruvate dehydrogenase kinase 4 mRNA in the liver and muscles of mice. Biol. Pharm. Bull., 26, 954-958.   DOI
7 Hsieh, M.C., Das, D., Sambandam, N., Zhang, M.Q. and Nahle, Z. (2008) Regulation of the PDK4 isozyme by the Rb-E2F1 complex. J. Biol. Chem., 283, 27410-27417.   DOI
8 Velpula, K.K., Bhasin, A., Asuthkar, S. and Tsung, A.J. (2013) Combined targeting of PDK1 and EGFR triggers regression of glioblastoma by reversing the Warburg effect. Cancer Res., 73, 7277-7289.   DOI
9 Heshe, D., Hoogestraat, S., Brauckmann, C., Karst, U., Boos, J. and Lanvers-Kaminsky, C. (2011) Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs. Cancer Chemother. Pharmacol., 67, 647-655.   DOI
10 Roche, T.E., Baker, J.C., Yan, X., Hiromasa, Y., Gong, X., Peng, T., Dong, J., Turkan, A. and Kasten, S.A. (2001) Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms. Prog. Nucleic Acid Res. Mol. Biol., 70, 33-75.   DOI
11 Bao, H., Kasten, S.A., Yan, X. and Roche, T.E. (2004) Pyruvate dehydrogenase kinase isoform 2 activity limited and further inhibited by slowing down the rate of dissociation of ADP. Biochemistry, 43, 13432-13441.   DOI
12 Kato, M., Li, J., Chuang, J.L. and Chuang, D.T. (2007) Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure, 15, 992-1004.   DOI
13 Klyuyeva, A., Tuganova, A. and Popov, K.M. (2007) Amino acid residues responsible for the recognition of dichloroacetate by pyruvate dehydrogenase kinase 2. FEBS Lett., 581, 2988-2992.   DOI
14 Li, J., Kato, M. and Chuang, D.T. (2009) Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate. J. Biol. Chem., 284, 34458-34467.   DOI
15 Evans, O.B. and Stacpoole, P.W. (1982) Prolonged hypolactatemia and increased total pyruvate dehydrogenase activity by dichloroacetate. Biochem. Pharmacol., 31, 1295-1300.   DOI
16 Curry, S.H., Chu, P.I., Baumgartner, T.G. and Stacpoole, P.W. (1985) Plasma concentrations and metabolic effects of intravenous sodium dichloroacetate. Clin. Pharmacol. Ther., 37, 89-93.   DOI
17 Stacpoole, P.W., Nagaraja, N.V. and Hutson, A.D. (2003) Efficacy of dichloroacetate as a lactate-lowering drug. J. Clin. Pharmacol., 43, 683-691.   DOI
18 Warburg, O. (1915) Notizen zur Entwickelungsphysiologie des Seeigeleies. Arch. f. d. ges. Physiol., 160, 324-332.   DOI
19 Warburg, O. (1923) Versuche an uberlebendem Carcinom-Gewebe (Methoden). Biochem. Zeitschr., 142, 317-333.
20 Warburg, O. (1924) Verbesserte Methode zur Messung der Atmung und Glykolyse. Biochem. Zeitschr., 152, 51-63.
21 Morten, K.J., Caky, M. and Matthews, P.M. (1998) Stabilization of the pyruvate dehydrogenase E1alpha subunit by dichloroacetate. Neurology, 51, 1331-1335.   DOI
22 Han, Z., Berendzen, K., Zhong, L., Surolia, I., Chouthai, N., Zhao, W., Maina, N., Srivastava, A. and Stacpoole, P.W. (2008) A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate. Mol. Genet. Metab., 93, 381-387.   DOI
23 Ishida, N., Kitagawa, M., Hatakeyama, S. and Nakayama, K. (2000) Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J. Biol. Chem., 275, 25146-25154.   DOI
24 Lu, K.P., Liou, Y.C. and Zhou, X.Z. (2002) Pinning down proline-directed phosphorylation signaling. Trends Cell Biol., 12, 164-172.   DOI
25 Virshup, D.M., Eide, E.J., Forger, D.B., Gallego, M. and Harnish, E.V. (2007) Reversible protein phosphorylation regulates circadian rhythms. Cold Spring Harb. Symp. Quant. Biol., 72, 413-420.
26 Moretto-Zita, M., Jin, H., Shen, Z., Zhao, T., Briggs, S.P. and Xu, Y. (2010) Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc. Natl. Acad. Sci. U.S.A., 107, 13312-13317.   DOI
27 Ozlu, N., Akten, B., Timm, W., Haseley, N., Steen, H. and Steen, J.A. (2010) Phosphoproteomics. Wiley Interdiscip. Rev. Syst. Biol. Med., 2, 255-276.
28 Thomas, L.W., Lam, C. and Edwards, S.W. (2010) Mcl-1; the molecular regulation of protein function. FEBS Lett., 584, 2981-2989.   DOI
29 Warburg, O. (1956) On respiratory impairment in cancer cells. Science, 124, 269-270.
30 Warburg, O. (1956) On the origin of cancer cells. Science, 123, 309-314.   DOI
31 Chance, B. and Castor, L.N. (1952) Some patterns of the respiratory pigments of ascites tumors of mice. Science, 116, 200-202.   DOI
32 Weinhouse, S. (1956) On respiratory impairment in cancer cells. Science, 124, 267-269.   DOI
33 Hanahan, D. and Weinberg, R.A. (2000) The hallmarks of cancer. Cell, 100, 57-70.   DOI
34 Yeung, S.J., Pan, J. and Lee, M.H. (2008) Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer. Cell. Mol. Life Sci., 65, 3981-3999.   DOI
35 Gatenby, R.A. and Gillies, R.J. (2004) Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer, 4, 891-899.   DOI
36 Brand, K.A. and Hermfisse, U. (1997) Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species. FASEB J., 11, 388-395.   DOI
37 Spitz, D.R., Sim, J.E., Ridnour, L.A., Galoforo, S.S. and Lee, Y.J. (2000) Glucose deprivation-induced oxidative stress in human tumor cells. A fundamental defect in metabolism? Ann. N. Y. Acad. Sci., 899, 349-362.
38 Elf, S.E. and Chen, J. (2014) Targeting glucose metabolism in patients with cancer. Cancer, 120, 774-780.   DOI
39 Hamanaka, R.B. and Chandel, N.S. (2009) Mitochondrial reactive oxygen species regulate hypoxic signaling. Curr. Opin. Cell Biol., 21, 894-899.   DOI
40 Geschwind, J.F., Georgiades, C.S., Ko, Y.H. and Pedersen, P.L. (2004) Recently elucidated energy catabolism pathways provide opportunities for novel treatments in hepatocellular carcinoma. Expert Rev. Anticancer Ther., 4, 449-457.   DOI
41 Buijs, M., Vossen, J.A., Geschwind, J.F., Ishimori, T., Engles, J.M., Acha-Ngwodo, O., Wahl, R.L. and Vali, M. (2009) Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer. Invest. New Drugs, 27, 120-123.   DOI
42 Ko, Y.H., Smith, B.L., Wang, Y., Pomper, M.G., Rini, D.A., Torbenson, M.S., Hullihen, J. and Pedersen, P.L. (2004) Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem. Biophys. Res. Commun., 324, 269-275.   DOI
43 Danial, N.N., Gramm, C.F., Scorrano, L., Zhang, C.Y., Krauss, S., Ranger, A.M., Datta, S.R., Greenberg, M.E., Licklider, L.J., Lowell, B.B., Gygi, S.P. and Korsmeyer, S.J. (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature, 424, 952-956.   DOI
44 Ganapathy-Kanniappan, S., Geschwind, J.F., Kunjithapatham, R., Buijs, M., Vossen, J.A., Tchernyshyov, I., Cole, R.N., Syed, L.H., Rao, P.P., Ota, S. and Vali, M. (2009) Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pyruvylated during 3-bromopyruvate mediated cancer cell death. Anticancer Res., 29, 4909-4918.
45 Ihrlund, L.S., Hernlund, E., Khan, O. and Shoshan, M.C. (2008) 3-Bromopyruvate as inhibitor of tumour cell energy metabolism and chemopotentiator of platinum drugs. Mol. Oncol., 2, 94-101.   DOI
46 Nachmansohn, D. (1979) German-Jewish Pioneers in Science, Springer, New York, pp. 1900-1933.
47 Hatefi, Y. (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu. Rev. Biochem., 54, 1015-1069.   DOI
48 Boguski, M.S., Lowe, T.M. and Tolstoshev, C.M. (1993) dbEST--database for "expressed sequence tags". Nat. Genet., 4, 332-333.   DOI
49 Altenberg, B. and Greulich, K.O. (2004) Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics, 84, 1014-1020.   DOI
50 Koppenol, W.H., Bounds, P.L. and Dang, C.V. (2011) Otto Warburg's contributions to current concepts of cancer metabolism. Nat. Rev. Cancer, 11, 325-337.   DOI
51 Parsons, D.W., Jones, S., Zhang, X., Lin, J.C., Leary, R.J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.M., Gallia, G.L., Olivi, A., McLendon, R., Rasheed, B.A., Keir, S., Nikolskaya, T., Nikolsky, Y., Busam, D.A., Tekleab, H., Diaz, L.A., Jr., Hartigan, J., Smith, D.R., Strausberg, R.L., Marie, S.K., Shinjo, S.M., Yan, H., Riggins, G.J., Bigner, D.D., Karchin, R., Papadopoulos, N., Parmigiani, G., Vogelstein, B., Velculescu, V.E. and Kinzler, K.W. (2008) An integrated genomic analysis of human glioblastoma multiforme. Science, 321, 1807-1812.   DOI
52 Bayley, J.P. and Devilee, P. (2010) Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? Curr. Opin. Genet. Dev., 20, 324-329.   DOI
53 Baysal, B.E., Willett-Brozick, J.E., Lawrence, E.C., Drovdlic, C.M., Savul, S.A., McLeod, D.R., Yee, H.A., Brackmann, D.E., Slattery, W.H., 3rd, Myers, E.N., Ferrell, R.E. and Rubinstein, W.S. (2002) Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. J. Med. Genet., 39, 178-183.   DOI
54 Morselli, E., Maiuri, M.C., Markaki, M., Megalou, E., Pasparaki, A., Palikaras, K., Criollo, A., Galluzzi, L., Malik, S.A., Vitale, I., Michaud, M., Madeo, F., Tavernarakis, N. and Kroemer, G. (2010) Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis., 1, e10.   DOI
55 Vali, M., Vossen, J.A., Buijs, M., Engles, J.M., Liapi, E., Ventura, V.P., Khwaja, A., Acha-Ngwodo, O., Ganapathy-Kanniappan, S., Syed, L., Wahl, R.L. and Geschwind, J.F. (2008) Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study. J. Pharmacol. Exp. Ther., 327, 32-37.   DOI
56 Xu, R.H., Pelicano, H., Zhou, Y., Carew, J.S., Feng, L., Bhalla, K.N., Keating, M.J. and Huang, P. (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res., 65, 613-621.
57 Blagosklonny, M.V. (2010) Linking calorie restriction to longevity through sirtuins and autophagy: any role for TOR. Cell Death Dis., 1, e12.   DOI
58 Willcox, D.C., Willcox, B.J., Todoriki, H. and Suzuki, M. (2009) The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. J. Am. Coll. Nutr., 28 Suppl, 500S-516S.   DOI
59 Ho, V.W., Leung, K., Hsu, A., Luk, B., Lai, J., Shen, S.Y., Minchinton, A.I., Waterhouse, D., Bally, M.B., Lin, W., Nelson, B.H., Sly, L.M. and Krystal, G. (2011) A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation. Cancer Res., 71, 4484-4493.   DOI
60 Bowker, S.L., Majumdar, S.R., Veugelers, P. and Johnson, J.A. (2006) Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care, 29, 254-258.   DOI
61 Martin-Puig, S., Temes, E., Olmos, G., Jones, D.R., Aragones, J. and Landazuri, M.O. (2004) Role of iron (II)-2-oxoglutarate-dependent dioxygenases in the generation of hypoxia-induced phosphatidic acid through HIF-1/2 and von Hippel-Lindau-independent mechanisms. J. Biol. Chem., 279, 9504-9511.   DOI
62 Baysal, B.E. (2007) A recurrent stop-codon mutation in succinate dehydrogenase subunit B gene in normal peripheral blood and childhood T-cell acute leukemia. PLoS ONE, 2, e436.   DOI
63 Tomlinson, I.P., Alam, N.A., Rowan, A.J., Barclay, E., Jaeger, E.E., Kelsell, D., Leigh, I., Gorman, P., Lamlum, H., Rahman, S., Roylance, R.R., Olpin, S., Bevan, S., Barker, K., Hearle, N., Houlston, R.S., Kiuru, M., Lehtonen, R., Karhu, A., Vilkki, S., Laiho, P., Eklund, C., Vierimaa, O., Aittomaki, K., Hietala, M., Sistonen, P., Paetau, A., Salovaara, R., Herva, R., Launonen, V., Aaltonen, L.A. and Multiple Leiomyoma Consortium (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet., 30, 406-410.   DOI
64 Semenza, G.L. (2012) Hypoxia-inducible factors in physiology and medicine. Cell, 148, 399-408.   DOI
65 Chen, H. and Costa, M. (2009) Iron- and 2-oxoglutaratedependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals, 22, 191-196.   DOI
66 Isaacs, J.S., Jung, Y.J., Mole, D.R., Lee, S., Torres-Cabala, C., Chung, Y.L., Merino, M., Trepel, J., Zbar, B., Toro, J., Ratcliffe, P.J., Linehan, W.M. and Neckers, L. (2005) HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell, 8, 143-153.   DOI
67 King, A., Selak, M.A. and Gottlieb, E. (2006) Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene, 25, 4675-4682.   DOI
68 Venkateswaran, V. and Klotz, L.H. (2010) Diet and prostate cancer: mechanisms of action and implications for chemoprevention. Nat. Rev. Urol., 7, 442-453.   DOI
69 Evans, J.M., Donnelly, L.A., Emslie-Smith, A.M., Alessi, D.R. and Morris, A.D. (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ, 330, 1304-1305.   DOI
70 Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., Myer, V.E., MacKeigan, J.P., Porter, J.A., Wang, Y.K., Cantley, L.C., Finan, P.M. and Murphy, L.O. (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell, 136, 521-534.   DOI
71 Nomura, D.K., Long, J.Z., Niessen, S., Hoover, H.S., Ng, S.W. and Cravatt, B.F. (2010) Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell, 140, 49-61.   DOI
72 Hursting, S.D., Lavigne, J.A., Berrigan, D., Perkins, S.N. and Barrett, J.C. (2003) Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu. Rev. Med., 54, 131-152.   DOI
73 El Mjiyad, N., Caro-Maldonado, A., Ramirez-Peinado, S. and Munoz-Pinedo, C. (2011) Sugar-free approaches to cancer cell killing. Oncogene, 30, 253-264.   DOI
74 Lee, C. and Longo, V.D. (2011) Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene, 30, 3305-3316.   DOI
75 Wallace, D.C. (2012) Mitochondria and cancer. Nat. Rev. Cancer, 12, 685-698.   DOI
76 Galluzzi, L., Kepp, O. and Kroemer, G. (2012) Mitochondria: master regulators of danger signalling. Nat. Rev. Mol. Cell Biol., 13, 780-788.   DOI
77 Gordan, J.D., Thompson, C.B. and Simon, M.C. (2007) HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell, 12, 108-113.   DOI
78 Goda, N. and Kanai, M. (2012) Hypoxia-inducible factors and their roles in energy metabolism. Int. J. Hematol., 95, 457-463.   DOI
79 Kim, J.W., Tchernyshyov, I., Semenza, G.L. and Dang, C.V. (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab., 3, 177-185.   DOI
80 Semenza, G.L., Roth, P.H., Fang, H.M. and Wang, G.L. (1994) Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J. Biol. Chem., 269, 23757-23763.
81 Selak, M.A., Armour, S.M., MacKenzie, E.D., Boulahbel, H., Watson, D.G., Mansfield, K.D., Pan, Y., Simon, M.C., Thompson, C.B. and Gottlieb, E. (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell, 7, 77-85.   DOI
82 Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.H., Ito, S., Yang, C., Wang, P., Xiao, M.T., Liu, L.X., Jiang, W.Q., Liu, J., Zhang, J.Y., Wang, B., Frye, S., Zhang, Y., Xu, Y.H., Lei, Q.Y., Guan, K.L., Zhao, S.M. and Xiong, Y. (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell, 19, 17-30.   DOI
83 Matoba, S., Kang, J.G., Patino, W.D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P.J., Bunz, F. and Hwang, P.M. (2006) p53 regulates mitochondrial respiration. Science, 312, 1650-1653.   DOI
84 Capuano, F., Guerrieri, F. and Papa, S. (1997) Oxidative phosphorylation enzymes in normal and neoplastic cell growth. J. Bioenerg. Biomembr., 29, 379-384.   DOI
85 Li, Y., Park, J., Piao, L., Kong, G., Kim, Y., Park, K.A., Zhang, T., Hong, J., Hur, G.M., Seok, J.H., Choi, S.W., Yoo, B.C., Hemmings, B.A., Brazil, D.P., Kim, S.H. and Park, J. (2013) PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage. Cell. Signal., 25, 74-84.   DOI
86 Cheon, J.M., Kim, D.I. and Kim, K.S. (2015) Insulin sensitivity improvement of fermented Korean Red Ginseng (Panax ginseng) mediated by insulin resistance hallmarks in old-aged ob/ob mice. J. Ginseng Res., 39, 331-337.   DOI
87 Kim, A.Y., Kwak, J.H., Je, N.K., Lee, Y.H. and Jung, Y.S. (2015) Epithelial-mesenchymal transition is associated with acquired resistance to 5-fluorocuracil in HT-29 colon cancer cells. Toxicol. Res., 31, 151-156.   DOI
88 Kim, I.S., Yang, S.Y., Han, J.H., Jung, S.H., Park, H.S. and Myung, C.S. (2015) Differential gene expression in GPR40-overexpressing pancreatic beta-cells treated with linoleic acid. Korean J. Physiol. Pharmacol., 19, 141-149.   DOI
89 Na, C.H., Hong, J.H., Kim, W.S., Shanta, S.R., Bang, J.Y., Park, D., Kim, H.K. and Kim, K.P. (2015) Identification of protein markers specific for papillary renal cell carcinoma using imaging mass spectrometry. Mol. Cells, 38, 624-629.   DOI
90 Liu, Y., Cao, Y., Zhang, W., Bergmeier, S., Qian, Y., Akbar, H., Colvin, R., Ding, J., Tong, L., Wu, S., Hines, J. and Chen, X. (2012) A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol. Cancer Ther., 11, 1672-1682.   DOI
91 Zhao, S., Lin, Y., Xu, W., Jiang, W., Zha, Z., Wang, P., Yu, W., Li, Z., Gong, L., Peng, Y., Ding, J., Lei, Q., Guan, K.L. and Xiong, Y. (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1${\alpha}$. Science, 324, 261-265.   DOI
92 Lopez-Rios, F., Sanchez-Arago, M., Garcia-Garcia, E., Ortega, A.D., Berrendero, J.R., Pozo-Rodriguez, F., Lopez-Encuentra, A., Ballestin, C. and Cuezva, J.M. (2007) Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas. Cancer Res., 67, 9013-9017.   DOI
93 Reitman, Z.J. and Yan, H. (2010) Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J. Natl. Cancer Inst., 102, 932-941.   DOI
94 Gross, S., Cairns, R.A., Minden, M.D., Driggers, E.M., Bittinger, M.A., Jang, H.G., Sasaki, M., Jin, S., Schenkein, D.P., Su, S.M., Dang, L., Fantin, V.R. and Mak, T.W. (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J. Exp. Med., 207, 339-344.   DOI
95 Cavalli, L.R., Varella-Garcia, M. and Liang, B.C. (1997) Diminished tumorigenic phenotype after depletion of mitochondrial DNA. Cell Growth Differ., 8, 1189-1198.
96 Tan, A.S., Baty, J.W., Dong, L.F., Bezawork-Geleta, A., Endaya, B., Goodwin, J., Bajzikova, M., Kovarova, J., Peterka, M., Yan, B., Pesdar, E.A., Sobol, M., Filimonenko, A., Stuart, S., Vondrusova, M., Kluckova, K., Sachaphibulkij, K., Rohlena, J., Hozak, P., Truksa, J., Eccles, D., Haupt, L.M., Griffiths, L.R., Neuzil, J. and Berridge, M.V. (2015) Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab., 21, 81-94.   DOI
97 Le, A., Cooper, C.R., Gouw, A.M., Dinavahi, R., Maitra, A., Deck, L.M., Royer, R.E., Vander Jagt, D.L., Semenza, G.L. and Dang, C.V. (2010) Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc. Natl. Acad. Sci. U.S.A., 107, 2037-2042.   DOI
98 Chan, D.A., Sutphin, P.D., Nguyen, P., Turcotte, S., Lai, E.W., Banh, A., Reynolds, G.E., Chi, J.T., Wu, J., Solow-Cordero, D.E., Bonnet, M., Flanagan, J.U., Bouley, D.M., Graves, E.E., Denny, W.A., Hay, M.P. and Giaccia, A.J. (2011) Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci. Transl. Med., 3, 94ra70.
99 Anastasiou, D., Yu, Y., Israelsen, W.J., Jiang, J.K., Boxer, M.B., Hong, B.S., Tempel, W., Dimov, S., Shen, M., Jha, A., Yang, H., Mattaini, K.R., Metallo, C.M., Fiske, B.P., Courtney, K.D., Malstrom, S., Khan, T.M., Kung, C., Skoumbourdis, A.P., Veith, H., Southall, N., Walsh, M.J., Brimacombe, K.R., Leister, W., Lunt, S.Y., Johnson, Z.R., Yen, K.E., Kunii, K., Davidson, S.M., Christofk, H.R., Austin, C.P., Inglese, J., Harris, M.H., Asara, J.M., Stephanopoulos, G., Salituro, F.G., Jin, S., Dang, L., Auld, D.S., Park, H.W., Cantley, L.C., Thomas, C.J. and Vander Heiden, M.G. (2012) Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat. Chem. Biol., 8, 839-847.   DOI
100 Kung, C., Hixon, J., Choe, S., Marks, K., Gross, S., Murphy, E., DeLaBarre, B., Cianchetta, G., Sethumadhavan, S., Wang, X., Yan, S., Gao, Y., Fang, C., Wei, W., Jiang, F., Wang, S., Qian, K., Saunders, J., Driggers, E., Woo, H.K., Kunii, K., Murray, S., Yang, H., Yen, K., Liu, W., Cantley, L.C., Vander Heiden, M.G., Su, S.M., Jin, S., Salituro, F.G. and Dang, L. (2012) Small molecule activation of PKM2 in cancer cells induces serine auxotrophy. Chem. Biol., 19, 1187-1198.   DOI
101 Shim, H., Dolde, C., Lewis, B.C., Wu, C.S., Dang, G., Jungmann, R.A., Dalla-Favera, R. and Dang, C.V. (1997) c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc. Natl. Acad. Sci. U.S.A., 94, 6658-6663.   DOI
102 Okar, D.A., Manzano, A., Navarro-Sabate, A., Riera, L., Bartrons, R. and Lange, A.J. (2001) PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. Trends Biochem. Sci., 26, 30-35.   DOI
103 Bensaad, K., Tsuruta, A., Selak, M.A., Vidal, M.N., Nakano, K., Bartrons, R., Gottlieb, E. and Vousden, K.H. (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell, 126, 107-120.   DOI
104 Green, D.R. and Chipuk, J.E. (2006) p53 and metabolism: Inside the TIGAR. Cell, 126, 30-32.   DOI
105 Fantin, V.R., St-Pierre, J. and Leder, P. (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell, 9, 425-434.   DOI
106 Cardone, R.A., Casavola, V. and Reshkin, S.J. (2005) The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat. Rev. Cancer, 5, 786-795.   DOI
107 Opavsky, R., Pastorekova, S., Zelnik, V., Gibadulinova, A., Stanbridge, E.J., Zavada, J., Kettmann, R. and Pastorek, J. (1996) Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. Genomics, 33, 480-487.   DOI
108 Ivanov, S., Liao, S.Y., Ivanova, A., Danilkovitch-Miagkova, A., Tarasova, N., Weirich, G., Merrill, M.J., Proescholdt, M.A., Oldfield, E.H., Lee, J., Zavada, J., Waheed, A., Sly, W., Lerman, M.I. and Stanbridge, E.J. (2001) Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Am. J. Pathol., 158, 905-919.   DOI
109 Sonveaux, P., Vegran, F., Schroeder, T., Wergin, M.C., Verrax, J., Rabbani, Z.N., De Saedeleer, C.J., Kennedy, K.M., Diepart, C., Jordan, B.F., Kelley, M.J., Gallez, B., Wahl, M.L., Feron, O. and Dewhirst, M.W. (2008) Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Invest., 118, 3930-3942.
110 Bhardwaj, R., Sharma, P.K., Jadon, S.P. and Varshney, R. (2012) A combination of 2-deoxy-D-glucose and 6-aminonicotinamide induces cell cycle arrest and apoptosis selectively in irradiated human malignant cells. Tumour Biol., 33, 1021-1030.   DOI
111 Michelakis, E.D., Webster, L. and Mackey, J.R. (2008) Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br. J. Cancer, 99, 989-994.   DOI
112 Strum, S.B., Adalsteinsson, O., Black, R.R., Segal, D., Peress, N.L. and Waldenfels, J. (2013) Case report: Sodium dichloroacetate (DCA) inhibition of the "Warburg Effect" in a human cancer patient: complete response in non-Hodgkin's lymphoma after disease progression with rituximab-CHOP. J. Bioenerg. Biomembr., 45, 307-315.   DOI
113 Addie, M., Ballard, P., Buttar, D., Crafter, C., Currie, G., Davies, B.R., Debreczeni, J., Dry, H., Dudley, P., Greenwood, R., Johnson, P.D., Kettle, J.G., Lane, C., Lamont, G., Leach, A., Luke, R.W., Morris, J., Ogilvie, D., Page, K., Pass, M., Pearson, S. and Ruston, L. (2013) Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases. J. Med. Chem., 56, 2059-2073.   DOI
114 Vaupel, P., Fortmeyer, H.P., Runkel, S. and Kallinowski, F. (1987) Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. Cancer Res., 47, 3496-3503.
115 Robertson, N., Potter, C. and Harris, A.L. (2004) Role of carbonic anhydrase IX in human tumor cell growth, survival, and invasion. Cancer Res., 64, 6160-6165.   DOI
116 Secomb, T.W., Hsu, R., Dewhirst, M.W., Klitzman, B. and Gross, J.F. (1993) Analysis of oxygen transport to tumor tissue by microvascular networks. Int. J. Radiat. Oncol. Biol. Phys., 25, 481-489.   DOI
117 Heldin, C.H., Rubin, K., Pietras, K. and Ostman, A. (2004) High interstitial fluid pressure - an obstacle in cancer therapy. Nat. Rev. Cancer, 4, 806-813.   DOI
118 Minchenko, O., Opentanova, I. and Caro, J. (2003) Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo. FEBS Lett., 554, 264-270.   DOI
119 Minchenko, O.H., Ogura, T., Opentanova, I.L., Minchenko, D.O. and Esumi, H. (2005) Splice isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4: expression and hypoxic regulation. Mol. Cell. Biochem., 280, 227-234.   DOI
120 Acker, T. and Plate, K.H. (2002) A role for hypoxia and hypoxia-inducible transcription factors in tumor physiology. J. Mol. Med., 80, 562-575.   DOI
121 Semenza, G.L. (2000) Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit. Rev. Biochem. Mol. Biol., 35, 71-103.   DOI
122 Barthel, A., Okino, S.T., Liao, J., Nakatani, K., Li, J., Whitlock, J.P., Jr. and Roth, R.A. (1999) Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J. Biol. Chem., 274, 20281-20286.   DOI
123 Chen, X., Qian, Y. and Wu, S. (2015) The Warburg effect: evolving interpretations of an established concept. Free Radic. Biol. Med., 79, 253-263.   DOI
124 Lin, J., Sampath, D., Nannini, M.A., Lee, B.B., Degtyarev, M., Oeh, J., Savage, H., Guan, Z., Hong, R., Kassees, R., Lee, L.B., Risom, T., Gross, S., Liederer, B.M., Koeppen, H., Skelton, N.J., Wallin, J.J., Belvin, M., Punnoose, E., Friedman, L.S. and Lin, K. (2013) Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin. Cancer Res., 19, 1760-1772.   DOI
125 Dumble, M., Crouthamel, M.C., Zhang, S.Y., Schaber, M., Levy, D., Robell, K., Liu, Q., Figueroa, D.J., Minthorn, E.A., Seefeld, M.A., Rouse, M.B., Rabindran, S.K., Heerding, D.A. and Kumar, R. (2014) Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS ONE, 9, e100880.   DOI
126 Hirai, H., Sootome, H., Nakatsuru, Y., Miyama, K., Taguchi, S., Tsujioka, K., Ueno, Y., Hatch, H., Majumder, P.K., Pan, B.S. and Kotani, H. (2010) MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol. Cancer Ther., 9, 1956-1967.   DOI
127 Bauer, D.E., Hatzivassiliou, G., Zhao, F., Andreadis, C. and Thompson, C.B. (2005) ATP citrate lyase is an important component of cell growth and transformation. Oncogene, 24, 6314-6322.   DOI
128 Taha, C., Liu, Z., Jin, J., Al-Hasani, H., Sonenberg, N. and Klip, A. (1999) Opposite translational control of GLUT1 and GLUT4 glucose transporter mRNAs in response to insulin. Role of mammalian target of rapamycin, protein kinase b, and phosphatidylinositol 3-kinase in GLUT1 mRNA translation. J. Biol. Chem., 274, 33085-33091.   DOI
129 Majewski, N., Nogueira, V., Bhaskar, P., Coy, P.E., Skeen, J.E., Gottlob, K., Chandel, N.S., Thompson, C.B., Robey, R.B. and Hay, N. (2004) Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol. Cell, 16, 819-830.   DOI
130 Majewski, N., Nogueira, V., Robey, R.B. and Hay, N. (2004) Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases. Mol. Cell. Biol., 24, 730-740.   DOI
131 Deberardinis, R.J., Lum, J.J. and Thompson, C.B. (2006) Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. J. Biol. Chem., 281, 37372-37380.   DOI
132 Albanell, J., Dalmases, A., Rovira, A. and Rojo, F. (2007) mTOR signalling in human cancer. Clin. Transl. Oncol., 9, 484-493.   DOI
133 Chiang, G.G. and Abraham, R.T. (2007) Targeting the mTOR signaling network in cancer. Trends Mol. Med., 13, 433-442.   DOI
134 Martin, D.E. and Hall, M.N. (2005) The expanding TOR signaling network. Curr. Opin. Cell Biol., 17, 158-166.   DOI
135 Dang, C.V. and Semenza, G.L. (1999) Oncogenic alterations of metabolism. Trends Biochem. Sci., 24, 68-72.   DOI
136 Hudson, C.C., Liu, M., Chiang, G.G., Otterness, D.M., Loomis, D.C., Kaper, F., Giaccia, A.J. and Abraham, R.T. (2002) Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol. Cell. Biol., 22, 7004-7014.   DOI
137 Mathupala, S.P., Rempel, A. and Pedersen, P.L. (1997) Aberrant glycolytic metabolism of cancer cells: a remarkable coordination of genetic, transcriptional, post-translational, and mutational events that lead to a critical role for type II hexokinase. J. Bioenerg. Biomembr., 29, 339-343.   DOI
138 Dang, C.V., Lewis, B.C., Dolde, C., Dang, G. and Shim, H. (1997) Oncogenes in tumor metabolism, tumorigenesis, and apoptosis. J. Bioenerg. Biomembr., 29, 345-354.   DOI
139 Lu, H., Forbes, R.A. and Verma, A. (2002) Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J. Biol. Chem., 277, 23111-23115.   DOI
140 Kim, J.W., Gao, P., Liu, Y.C., Semenza, G.L. and Dang, C.V. (2007) 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., 27, 7381-7393.   DOI
141 Schwartzenberg-Bar-Yoseph, F., Armoni, M. and Karnieli, E. (2004) The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res., 64, 2627-2633.   DOI
142 Kawauchi, K., Araki, K., Tobiume, K. and Tanaka, N. (2008) p53 regulates glucose metabolism through an IKK-NF-${\kappa}$B pathway and inhibits cell transformation. Nat. Cell Biol., 10, 611-618.   DOI
143 Draoui, N. and Feron, O. (2011) Lactate shuttles at a glance: from physiological paradigms to anti-cancer treatments. Dis. Model. Mech., 4, 727-732.   DOI
144 Kondoh, H., Lleonart, M.E., Gil, J., Wang, J., Degan, P., Peters, G., Martinez, D., Carnero, A. and Beach, D. (2005) Glycolytic enzymes can modulate cellular life span. Cancer Res., 65, 177-185.
145 Beckert, S., Farrahi, F., Aslam, R.S., Scheuenstuhl, H., Konigsrainer, A., Hussain, M.Z. and Hunt, T.K. (2006) Lactate stimulates endothelial cell migration. Wound Repair Regen., 14, 321-324.   DOI
146 Vegran, F., Boidot, R., Michiels, C., Sonveaux, P. and Feron, O. (2011) Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-${\kappa}$B/IL-8 pathway that drives tumor angiogenesis. Cancer Res., 71, 2550-2560.   DOI
147 Hirschhaeuser, F., Sattler, U.G. and Mueller-Klieser, W. (2011) Lactate: a metabolic key player in cancer. Cancer Res., 71, 6921-6925.   DOI
148 Kurtoglu, M., Maher, J.C. and Lampidis, T.J. (2007) Differential toxic mechanisms of 2-deoxy-D-glucose versus 2-fluorodeoxy-D-glucose in hypoxic and normoxic tumor cells. Antioxid. Redox Signal., 9, 1383-1390.   DOI
149 Bandugula, V.R. and N, R.P. (2013) 2-Deoxy-D-glucose and ferulic acid modulates radiation response signaling in nonsmall cell lung cancer cells. Tumour Biol., 34, 251-259.   DOI
150 Giammarioli, A.M., Gambardella, L., Barbati, C., Pietraforte, D., Tinari, A., Alberton, M., Gnessi, L., Griffin, R.J., Minetti, M. and Malorni, W. (2012) Differential effects of the glycolysis inhibitor 2-deoxy-D-glucose on the activity of pro-apoptotic agents in metastatic melanoma cells, and induction of a cytoprotective autophagic response. Int. J. Cancer, 131, E337-E347.   DOI
151 Zagorodna, O., Martin, S.M., Rutkowski, D.T., Kuwana, T., Spitz, D.R. and Knudson, C.M. (2012) 2-Deoxyglucose-induced toxicity is regulated by Bcl-2 family members and is enhanced by antagonizing Bcl-2 in lymphoma cell lines. Oncogene, 31, 2738-2749.   DOI
152 Ralser, M., Wamelink, M.M., Struys, E.A., Joppich, C., Krobitsch, S., Jakobs, C. and Lehrach, H. (2008) A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth. Proc. Natl. Acad. Sci. U.S.A., 105, 17807-17811.   DOI
153 Urakami, K., Zangiacomi, V., Yamaguchi, K. and Kusuhara, M. (2013) Impact of 2-deoxy-D-glucose on the target metabolome profile of a human endometrial cancer cell line. Biomed. Res., 34, 221-229.   DOI
154 Robinson, G.L., Dinsdale, D., Macfarlane, M. and Cain, K. (2012) Switching from aerobic glycolysis to oxidative phosphorylation modulates the sensitivity of mantle cell lymphoma cells to TRAIL. Oncogene, 31, 4996-5006.   DOI
155 Golding, J.P., Wardhaugh, T., Patrick, L., Turner, M., Phillips, J.B., Bruce, J.I. and Kimani, S.G. (2013) Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy. Br. J. Cancer, 109, 976-982.   DOI
156 Kim, S.M., Yun, M.R., Hong, Y.K., Solca, F., Kim, J.H., Kim, H.J. and Cho, B.C. (2013) Glycolysis inhibition sensitizes non-small cell lung cancer with T790M mutation to irreversible EGFR inhibitors via translational suppression of Mcl-1 by AMPK activation. Mol. Cancer Ther., 12, 2145-2156.   DOI
157 Wood, T.E., Dalili, S., Simpson, C.D., Hurren, R., Mao, X., Saiz, F.S., Gronda, M., Eberhard, Y., Minden, M.D., Bilan, P.J., Klip, A., Batey, R.A. and Schimmer, A.D. (2008) A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death. Mol. Cancer Ther., 7, 3546-3555.   DOI
158 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. and Lampidis, T.J. (2013) 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., 71, 523-530.   DOI
159 Yamaguchi, R., Janssen, E., Perkins, G., Ellisman, M., Kitada, S. and Reed, J.C. (2011) Efficient elimination of cancer cells by deoxyglucose-ABT-263/737 combination therapy. PLoS ONE, 6, e24102.   DOI
160 Maher, J.C., Wangpaichitr, M., Savaraj, N., Kurtoglu, M. and Lampidis, T.J. (2007) Hypoxia-inducible factor-1 confers resistance to the glycolytic inhibitor 2-deoxy-D-glucose. Mol. Cancer Ther., 6, 732-741.
161 Stacpoole, P.W. (1969) Review of the pharmacologic and therapeutic effects of diisopropylammonium dichloroacetate (DIPA). J. Clin. Pharmacol. J. New Drugs, 9, 282-291.
162 Stacpoole, P.W. and Felts, J.M. (1970) Diisopropylammonium dichloroacetate (DIPA) and sodium dichloracetate (DCA): effect on glucose and fat metabolism in normal and diabetic tissue. Metabolism, 19, 71-78.   DOI
163 Whitehouse, S. and Randle, P.J. (1973) Activation of pyruvate dehydrogenase in perfused rat heart by dichloroacetate (Short Communication). Biochem. J., 134, 651-653.   DOI
164 Stacpoole, P.W., Moore, G.W. and Kornhauser, D.M. (1978) Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia. N. Engl. J. Med., 298, 526-530.   DOI
165 Stacpoole, P.W. (1989) The pharmacology of dichloroacetate. Metabolism, 38, 1124-1144.   DOI
166 Stacpoole, P.W., Kerr, D.S., Barnes, C., Bunch, S.T., Carney, P.R., Fennell, E.M., Felitsyn, N.M., Gilmore, R.L., Greer, M., Henderson, G.N., Hutson, A.D., Neiberger, R.E., O'Brien, R.G., Perkins, L.A., Quisling, R.G., Shroads, A.L., Shuster, J.J., Silverstein, J.H., Theriaque, D.W. and Valenstein, E. (2006) Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics, 117, 1519-1531.   DOI
167 Bersin, R.M. and Stacpoole, P.W. (1997) Dichloroacetate as metabolic therapy for myocardial ischemia and failure. Am. Heart J., 134, 841-855.   DOI
168 Stacpoole, P.W., Harman, E.M., Curry, S.H., Baumgartner, T.G. and Misbin, R.I. (1983) Treatment of lactic acidosis with dichloroacetate. N. Engl. J. Med., 309, 390-396.   DOI
169 Stacpoole, P.W., Wright, E.C., Baumgartner, T.G., Bersin, R.M., Buchalter, S., Curry, S.H., Duncan, C.A., Harman, E.M., Henderson, G.N., Jenkinson, S., et al. (1992) A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. N. Engl. J. Med., 327, 1564-1569.   DOI
170 Stacpoole, P.W., Gilbert, L.R., Neiberger, R.E., Carney, P.R., Valenstein, E., Theriaque, D.W. and Shuster, J.J. (2008) Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate. Pediatrics, 121, e1223-e1228.   DOI
171 Berendzen, K., Theriaque, D.W., Shuster, J. and Stacpoole, P.W. (2006) Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency. Mitochondrion, 6, 126-135.   DOI
172 Kaufmann, P., Engelstad, K., Wei, Y., Jhung, S., Sano, M.C., Shungu, D.C., Millar, W.S., Hong, X., Gooch, C.L., Mao, X., Pascual, J.M., Hirano, M., Stacpoole, P.W., DiMauro, S. and De Vivo, D.C. (2006) Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology, 66, 324-330.   DOI