JOURNAL BROWSE
Search
Advanced SearchSearch Tips
Targeting Cancer Metabolism - Revisiting the Warburg Effects
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Toxicological Research
  • Volume 32, Issue 3,  2016, pp.177-193
  • Publisher : The Korean Society of Toxicology
  • DOI : 10.5487/TR.2016.32.3.177
 Title & Authors
Targeting Cancer Metabolism - Revisiting the Warburg Effects
Tran, Quangdon; Lee, Hyunji; Park, Jisoo; Kim, Seon-Hwan; Park, Jongsun;
  PDF(new window)
 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;
 Language
English
 Cited by
1.
Manipulating carbohydrate metabolism to enhance regeneration (retrospective on DOI 10.1002/bies.201300110), BioEssays, 2016  crossref(new windwow)
 References
1.
Warburg, O. (1915) Notizen zur Entwickelungsphysiologie des Seeigeleies. Arch. f. d. ges. Physiol., 160, 324-332. crossref(new window)

2.
Warburg, O. (1923) Versuche an uberlebendem Carcinom-Gewebe (Methoden). Biochem. Zeitschr., 142, 317-333.

3.
Warburg, O. (1924) Verbesserte Methode zur Messung der Atmung und Glykolyse. Biochem. Zeitschr., 152, 51-63.

4.
Warburg, O. (1956) On the origin of cancer cells. Science, 123, 309-314. crossref(new window)

5.
Warburg, O. (1956) On respiratory impairment in cancer cells. Science, 124, 269-270.

6.
Chance, B. and Castor, L.N. (1952) Some patterns of the respiratory pigments of ascites tumors of mice. Science, 116, 200-202. crossref(new window)

7.
Weinhouse, S. (1956) On respiratory impairment in cancer cells. Science, 124, 267-269. crossref(new window)

8.
Hanahan, D. and Weinberg, R.A. (2000) The hallmarks of cancer. Cell, 100, 57-70. crossref(new window)

9.
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. crossref(new window)

10.
Gatenby, R.A. and Gillies, R.J. (2004) Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer, 4, 891-899. crossref(new window)

11.
Brand, K.A. and Hermfisse, U. (1997) Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species. FASEB J., 11, 388-395.

12.
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.

13.
Elf, S.E. and Chen, J. (2014) Targeting glucose metabolism in patients with cancer. Cancer, 120, 774-780. crossref(new window)

14.
Hamanaka, R.B. and Chandel, N.S. (2009) Mitochondrial reactive oxygen species regulate hypoxic signaling. Curr. Opin. Cell Biol., 21, 894-899. crossref(new window)

15.
Hatefi, Y. (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu. Rev. Biochem., 54, 1015-1069. crossref(new window)

16.
Boguski, M.S., Lowe, T.M. and Tolstoshev, C.M. (1993) dbEST--database for "expressed sequence tags". Nat. Genet., 4, 332-333. crossref(new window)

17.
Altenberg, B. and Greulich, K.O. (2004) Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics, 84, 1014-1020. crossref(new window)

18.
Nachmansohn, D. (1979) German-Jewish Pioneers in Science, Springer, New York, pp. 1900-1933.

19.
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. crossref(new window)

20.
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. crossref(new window)

21.
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. crossref(new window)

22.
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. crossref(new window)

23.
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. crossref(new window)

24.
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. crossref(new window)

25.
Semenza, G.L. (2012) Hypoxia-inducible factors in physiology and medicine. Cell, 148, 399-408. crossref(new window)

26.
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. crossref(new window)

27.
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. crossref(new window)

28.
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. crossref(new window)

29.
King, A., Selak, M.A. and Gottlieb, E. (2006) Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene, 25, 4675-4682. crossref(new window)

30.
Goda, N. and Kanai, M. (2012) Hypoxia-inducible factors and their roles in energy metabolism. Int. J. Hematol., 95, 457-463. crossref(new window)

31.
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. crossref(new window)

32.
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.

33.
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. crossref(new window)

34.
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. crossref(new window)

35.
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. crossref(new window)

36.
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. crossref(new window)

37.
Capuano, F., Guerrieri, F. and Papa, S. (1997) Oxidative phosphorylation enzymes in normal and neoplastic cell growth. J. Bioenerg. Biomembr., 29, 379-384. crossref(new window)

38.
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. crossref(new window)

39.
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. crossref(new window)

40.
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. crossref(new window)

41.
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. crossref(new window)

42.
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.

43.
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. crossref(new window)

44.
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. crossref(new window)

45.
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. crossref(new window)

46.
Green, D.R. and Chipuk, J.E. (2006) p53 and metabolism: Inside the TIGAR. Cell, 126, 30-32. crossref(new window)

47.
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. crossref(new window)

48.
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. crossref(new window)

49.
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. crossref(new window)

50.
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. crossref(new window)

51.
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. crossref(new window)

52.
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. crossref(new window)

53.
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. crossref(new window)

54.
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. crossref(new window)

55.
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.

56.
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. crossref(new window)

57.
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. crossref(new window)

58.
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. crossref(new window)

59.
Semenza, G.L. (2000) Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit. Rev. Biochem. Mol. Biol., 35, 71-103. crossref(new window)

60.
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. crossref(new window)

61.
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. crossref(new window)

62.
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. crossref(new window)

63.
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. crossref(new window)

64.
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. crossref(new window)

65.
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. crossref(new window)

66.
Albanell, J., Dalmases, A., Rovira, A. and Rojo, F. (2007) mTOR signalling in human cancer. Clin. Transl. Oncol., 9, 484-493. crossref(new window)

67.
Chiang, G.G. and Abraham, R.T. (2007) Targeting the mTOR signaling network in cancer. Trends Mol. Med., 13, 433-442. crossref(new window)

68.
Martin, D.E. and Hall, M.N. (2005) The expanding TOR signaling network. Curr. Opin. Cell Biol., 17, 158-166. crossref(new window)

69.
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. crossref(new window)

70.
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. crossref(new window)

71.
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. crossref(new window)

72.
Dang, C.V. and Semenza, G.L. (1999) Oncogenic alterations of metabolism. Trends Biochem. Sci., 24, 68-72. crossref(new window)

73.
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. crossref(new window)

74.
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. crossref(new window)

75.
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. crossref(new window)

76.
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. crossref(new window)

77.
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.

78.
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. crossref(new window)

79.
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. crossref(new window)

80.
Draoui, N. and Feron, O. (2011) Lactate shuttles at a glance: from physiological paradigms to anti-cancer treatments. Dis. Model. Mech., 4, 727-732. crossref(new window)

81.
Hirschhaeuser, F., Sattler, U.G. and Mueller-Klieser, W. (2011) Lactate: a metabolic key player in cancer. Cancer Res., 71, 6921-6925. crossref(new window)

82.
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. crossref(new window)

83.
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. crossref(new window)

84.
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. crossref(new window)

85.
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. crossref(new window)

86.
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. crossref(new window)

87.
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. crossref(new window)

88.
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. crossref(new window)

89.
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. crossref(new window)

90.
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. crossref(new window)

91.
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. crossref(new window)

92.
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. crossref(new window)

93.
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.

94.
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. crossref(new window)

95.
Stacpoole, P.W. (1969) Review of the pharmacologic and therapeutic effects of diisopropylammonium dichloroacetate (DIPA). J. Clin. Pharmacol. J. New Drugs, 9, 282-291.

96.
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. crossref(new window)

97.
Whitehouse, S. and Randle, P.J. (1973) Activation of pyruvate dehydrogenase in perfused rat heart by dichloroacetate (Short Communication). Biochem. J., 134, 651-653. crossref(new window)

98.
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. crossref(new window)

99.
Stacpoole, P.W. (1989) The pharmacology of dichloroacetate. Metabolism, 38, 1124-1144. crossref(new window)