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Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy

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DOI: 10.4236/ijcm.2011.22022    6,299 Downloads   12,927 Views   Citations


It is well known that malignant cells have accelerated glucose uptake and metabolism in order to maintain their fast proliferation rates. With the increased influx of glucose into cancer cells, glycolysis is facilitated through a coordinated regulation of metabolic enzymes and pyruvate consumption. Shiftting from mitochondrial oxidative phosphorylation to glycolysis and other pathways such as pentose phosphate pathway (PPP) and de novo fatty acid synthesis in the breast tumor provides not only energy but also the materials needed for cell proliferation. Glucose augmentation in tumor cells can be due to the elevated level of glucose transporter (GLUT) proteins, such as the over-expression of GLUT1 and expression of GLUT5 in breast cancers. Moreover, other factors such as hypoxia-inducible factor-1 (HIF-1), estrogen and growth factors are important modulators of glucose metabolism in the progression of breast carcinomas. Therapies targeting at the glycolytic pathway, fatty acid synthesis and GLUTs expression are currently being investigated. Restoring tumor cells to its normal glucose metabolic state would endow tumor specific and accessible treatment that targets glucose metabolism.

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The authors declare no conflicts of interest.

Cite this paper

N. Li, W. Tan, J. Li, P. Li, S. Lee, Y. Wang and Y. Gong, "Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy," International Journal of Clinical Medicine, Vol. 2 No. 2, 2011, pp. 110-128. doi: 10.4236/ijcm.2011.22022.


[1] [1] O. Warburg, “On the Origin of Cancer Cells,” Science, Vol. 123, No. 3191, 1956, pp. 309-314. doi:10.1126/science.123.3191.309
[2] [2] H. Simonnet, et al., “Low Mitochondrial Respiratory Chain Content Correlates with Tumor Aggressiveness in Renal Cell Carcinoma,” Carcinogenesis, Vol. 23, No. 5, 2002, pp. 759-768. doi:10.1093/carcin/23.5.759
[3] [3] V. Ganapathy, M. Thangaraju, and P. D. Prasad, “Nutri-ent Transporters in Cancer: Relevance to Warburg Hy-pothesis and Beyond,” Pharmacology & Therapeutics, Vol. 121, No. 1, 2009, pp. 29-40. doi:10.1016/j.pharmthera.2008.09.005
[4] [4] M. Board, S. Humm and E. A. Newsholme, “Maximum Activities of Key Enzymes of Glycolysis, Glutaminolysis, Pentose Phosphate Pathway and Tricarboxylic Acid Cycle in Normal, Neoplastic and Suppressed Cells,” Bio- chemical Journal, Vol. 265, No. 2, 1990, pp. 503-509.
[5] [5] A. Hennipman, et al., “Glycolytic Enzymes in Breast Cancer, Benign Breast Disease and Normal Breast Tis-sue,” Tumor Biology, Vol. 8, No. 5, 1987, pp. 251-263. doi:10.1159/000217529
[6] [6] S. Mazurek, H. Grimm, C. B. Boschek, P. Vaupel and E. Eigenbrodt, “Pyruvate Kinase Type M2: A Crossroad in the Tumor Metabolome,” British Journal of Nutrition, Vol. 87, Suppl 1, 2002, pp. S23-S29. doi:10.1079/BJN2001454
[7] [7] J. A. Cooper, N. A. Reiss, R. J. Schwartz and T. Hunter, “Three Glycolytic Enzymes are Phosphorylated at Tyro-sine in Cells Transformed by Rous Sarcoma Virus,” Na-ture, Vol. 302, No. 5905, 1983, pp. 218-223. doi:10.1038/302218a0
[8] [8] M. I. Koukourakis, A. Giatromanolaki, C. Simopoulos, A. Polychronidis and E. Sivridis, “Lactate Dehydrogenase 5 (LDH5) Relates to up-Regulated Hypoxia Inducible Fac-tor Pathway and Metastasis in Colorectal Cancer,” Clinical and Experimental Metastasis, Vol. 22, No. 1, 2005, pp. 25-30. doi:10.1007/s10585-005-2343-7
[9] [9] J. W. Kim and C. V. Dang, “Cancer’s Molecular Sweet Tooth and the Warburg Effect,” Cancer Research, Vol. 66, No. 18, 2006, pp. 8927-8930. doi:10.1158/0008-5472.CAN-06-1501
[10] [10] S. P. Mathupala, C. Heese and P. L. Pedersen, “Glucose Catabolism in Cancer Cells. The Type 2 Hexokinase Promoter Contains Functionally Active Response Ele-ments for the Tumor Suppressor P53,” Journal of Bio-logical Chemistry, Vol. 272, No. 36, 1997, pp. 22776-22780. doi:10.1074/jbc.272.36.22776
[11] [11] J. D. Gordan and M. C. Simon, “Hypoxia-Inducible Fac-tors: Central Regulators of the Tumor Phenotype,” Cur-rent Opinion in Genetics & Development, Vol. 17, No. 1, 2007, pp. 71-77. doi:10.1016/j.gde.2006.12.006
[12] [12] G. L. Semenza, “Hypoxia-Inducible Factor 1 (Hif-1) Pathway,” Science’s STKE, Vol. 2007, No. 407, 2007, p. cm8. doi:10.1126/stke.4072007cm8
[13] [13] J. W. Kim and C. V. Dang, “Multifaceted Roles of Gly-colytic Enzymes,” Trends in Biochemical Sciences, Vol. 30, No. 3, 2005, pp. 142-150. doi:10.1016/j.tibs.2005.01.005
[14] [14] K. H. Ibsen, et al., “Expression of Multimolecular Forms of Pyruvate Kinase in Normal, Benign, and Malignant Human Breast Tissue,” Cancer Research, Vol. 42, No. 3, 1982, pp. 888-892.
[15] [15] L. G. Baggetto, “Deviant Energetic Metabolism of Gly-colytic Cancer Cells,” Biochimie, Vol. 74, No. 11, 1992, pp. 959-974. doi:10.1016/0300-9084(92)90016-8
[16] [16] P. S. Coleman and B. B. Lavietes, “Membrane Choles-terol, Tumorigenesis, and the Biochemical Phenotype of Neoplasia,” CRC Critical Reviews in Biochemistry, Vol. 11, No. 4, 1981, pp. 341-393.
[17] [17] W. L. McKeehan, “Glycolysis, Glutaminolysis and Cell Proliferation,” Cell Biology International Reports, Vol. 6, No. 7, 1982, pp. 635-650. doi:10.1016/0309-1651(82)90125-4
[18] [18] Z. Kovacevic and J. D. McGivan, “Mitochondrial Me-tabolism of Glutamine and Glutamate and Its Physiologi-cal Significance,” Physiological Reviews, Vol. 63, No. 2, 1983, pp. 547-605.
[19] [19] H. Shim, et al., “C-Myc Transactivation of Ldh-A: Im-plications for Tumor Metabolism and Growth,” Proceed-ings of the National Academy of Sciences of the USA, Vol. 94, No. 13, 1997, pp. 6658-6663. doi:10.1073/pnas.94.13.6658
[20] [20] C. V. Dang and G. L. Semenza, “Oncogenic Alterations of Metabolism,” Trends in Biochemical Sciences, Vol. 24, No. 2, 1999, pp. 68-72. doi:10.1016/S0968-0004(98)01344-9
[21] [21] G. L. Semenza, P. H. Roth, H. M. Fang and G. L. Wang, “Transcriptional Regulation of Genes Encoding Glyco-lytic Enzymes by Hypoxia-Inducible Factor 1,” Journal of Biological Chemistry, Vol. 269, No. 38, 1994, pp. 23757-23763.
[22] [22] J. W. Kim, I. Tchernyshyov, G. L. Semenza and C. V. Dang, “Hif-1-Mediated Expression of Pyruvate Dehy-drogenase Kinase: A Metabolic Switch Required for Cel-lular Adaptation to Hypoxia,” Cell Metabolism, Vol. 3, No. 3, 2006, pp. 177-185. doi:10.1016/j.cmet.2006.02.002
[23] [23] I. Papandreou, R. A. Cairns, L. Fontana, A. L. Lim and N. C. Denko, “Hif-1 Mediates Adaptation to Hypoxia by Actively Downregulating Mitochondrial Oxygen Con-sumption,” Cell Metabolism, Vol. 3, No. 3, 2006, pp. 187-197. doi:10.1016/j.cmet.2006.01.012
[24] [24] E. D. Michelakis, L. Webster and J. R. Mackey, “Di-chloroacetate (Dca) as a Potential Metabolic-Targeting Therapy for Cancer,” British Journal of Cancer, Vol. 99, No. 7, 2008, pp. 989-994. doi:10.1038/sj.bjc.6604554
[25] [25] J. Chesney, “6-Phosphofructo-2-Kinase/Fructose-2, 6-Bisphosphatase and Tumor Cell Glycolysis,” Curr Opin Current Opinion in Clinical Nutrition & Metabolic Care, Vol. 9, No. 5, 2006, pp. 535-539. doi:10.1097/01.mco.0000241661.15514.fb
[26] [26] G.L. Semenza, et al., “Hypoxia Response Elements in the Aldolase a, Enolase 1, and Lactate Dehydrogenase a Gene Promoters Contain Essential Binding Sites for Hy-poxia-Inducible Factor 1,” Journal of Biological Chemis-try, Vol. 271, No. 51, 1996, pp. 32529-32537. doi:10.1074/jbc.271.51.32529
[27] [27] V.R. Fantin, J. St-Pierre, and P. Leder, “Attenuation of Ldh-a Expression Uncovers a Link between Glycolysis, Mitochondrial Physiology, and Tumor Maintenance,” Cancer Cell, Vol. 9, No. 6, 2006, pp. 425-434. doi:10.1016/j.ccr.2006.04.023
[28] [28] M. Wu, et al., “Multiparameter Metabolic Analysis Re-veals a Close Link between Attenuated Mitochondrial Bioenergetic Function and Enhanced Glycolysis De-pendency in Human Tumor Cells,” American Journal of Physiology-Cell Physiology, Vol. 292, No. 1, 2007, pp. C125-C136. doi:10.1152/ajpcell.00247.2006
[29] [29] J. G. Pastorino, J. B. Hoek and N. Shulga, “Activation of Glycogen Synthase Kinase 3beta Disrupts the Binding of Hexokinase 2 to Mitochondria by Phosphorylating Volt-age-Dependent Anion Channel and Potentiates Chemo-therapy-Induced Cytotoxicity,” Cancer Research, Vol. 65, No. 22, 2005, pp. 10545-10554. doi:10.1158/0008-5472.CAN-05-1925
[30] [30] J. G. Pan and T. W. Mak, “Metabolic Targeting as an Anticancer Strategy: Dawn of a New Era?” Science’s STKE, Vol. 2007, No. 381, 2007, pp. pe14.
[31] [31] R. L. Elstrom, et al., “Akt Stimulates Aerobic Glycolysis in Cancer Cells,” Cancer Resarch, Vol. 64, No. 11, 2004, pp. 3892-3899. doi:10.1158/0008-5472.CAN-03-2904
[32] [32] K. Gottlob, et al., “Inhibition of Early Apoptotic Events by Akt/Pkb Is Dependent on the First Committed Step of Glycolysis and Mitochondrial Hexokinase,” Genes & Development, Vol. 15, No. 11, 2001, pp. 1406-1418. doi:10.1101/gad.889901
[33] [33] K. Bensaad, et al., “Tigar, a P53-Inducible Regulator of Glycolysis and Apoptosis,” Cell, Vol. 126, No. 1, 2006, pp. 107-120. doi:10.1016/j.cell.2006.05.036
[34] [34] S. Matoba, et al., “P53 Regulates Mitochondrial Respira- tion,” Science, Vol. 312, No. 5780, 2006, pp. 1650-1653. doi:10.1126/science.1126863
[35] [35] M. C. Brahimi-Horn, J. Chiche and J. Pouyssegur, “Hy-poxia Signalling Controls Metabolic Demand,” Current Opinion in Cell Biology, Vol. 19, No. 2, 2007, pp. 223-229. doi:10.1016/
[36] [36] F. Dayan, N. M. Mazure, M. C. Brahimi-Horn and J. Pouyssegur, “A Dialogue between the Hypoxia-Inducible Factor and the Tumor Microenvironment,” Cancer Mi-croenvironment, Vol. 1, No. 1, 2008, pp. 53-68.
[37] [37] S. Zhou, et al., “Frequency and Phenotypic Implications of Mitochondrial DNA Mutations in Human Squamous Cell Cancers of the Head and Neck,” Proceedings of the National Academy of Sciences of the USA, Vol. 104, No. 18, 2007, pp. 7540-7545. doi:10.1073/pnas.0610818104
[38] [38] S. Dasgupta, M. O. Hoque, S. Upadhyay and D. Sid-ransky, “Mitochondrial Cytochrome B Gene Mutation Promotes Tumor Growth in Bladder Cancer,” Cancer Research, Vol. 68, No. 3, 2008, pp. 700-706. doi:10.1158/0008-5472.CAN-07-5532
[39] [39] W. C. Copeland, J. T. Wachsman, F. M. Johnson and J. S. Penta, “Mitochondrial DNA Alterations in Cancer,” Cancer Investigation, Vol. 20, No. 4, 2002, pp. 557-569. doi:10.1081/CNV-120002155
[40] [40] B. E. Baysal, “Role of Mitochondrial Mutations in Can-cer,” Endocrine Pathology, Vol. 17, No. 3, 2006, pp. 203-212. doi:10.1385/EP:17:3:203
[41] [41] J. S. Carew and P. Huang, “Mitochondrial Defects in Cancer,” Molecular Cancer, Vol. 1, 2002, pp. 9. doi:10.1186/1476-4598-1-9
[42] [42] K. Plak, A. M. Czarnecka, T. Krawczyk, P. Golik and E. Bartnik, “Breast Cancer as a Mitochondrial Disorder (Re-view),” Oncology Reports,Vol. 21, No. 4, 2009, pp. 845-851.
[43] [43] T. Pfeiffer, S. Schuster and S. Bonhoeffer, “Cooperation and Competition in the Evolution of Atp-Producing Pathways,” Science, Vol. 292, No. 5516, 2001, pp. 504-507. doi:10.1126/science.1058079
[44] [44] N. Bellance, P. Lestienne and R. Rossignol, “Mitochon-dria: From Bioenergetics to the Metabolic Regulation of Carcinogenesis,” Frontiers in Bioscience, Vol. 14, 2009, pp. 4015-4034.
[45] [45] J. S. Modica-Napolitano and K. K. Singh, “Mitochondrial Dysfunction in Cancer,” Mitochondrion, Vol. 4, No. 5-6, 2004, pp. 755-762. doi:10.1016/j.mito.2004.07.027
[46] [46] R. G. Jones and C. B. Thompson, “Tumor Suppressors and Cell Metabolism: A Recipe for Cancer Growth,” Genes & Development, Vol. 23, No. 5, 2009, pp. 537-548. doi:10.1101/gad.1756509
[47] [47] D. E. Bauer, G. Hatzivassiliou, F. Zhao, C. Andreadis, and C. B. Thompson, “Atp Citrate Lyase is an Important Component of Cell Growth and Transformation,” Onco-gene, Vol. 24, No. 41, 2005, pp. 6314-6322. doi:10.1038/sj.onc.1208773
[48] [48] X. Tong, F. Zhao and C. B. Thompson, “The Molecular Determinants of De Novo Nucleotide Biosynthesis in Cancer Cells,” Current Opinion in Genetics & Develop-ment, Vol. 19, No. 1, 2009, pp. 32-37. doi:10.1016/j.gde.2009.01.002
[49] [49] T. Wood, “Physiological Functions of the Pentose Phos-phate Pathway,” Cell Biochemistry and Function, Vol. 4, No. 4, 1986, pp. 241-247. doi:10.1002/cbf.290040403
[50] [50] E. W. McDermott, E. T. Barron, P. P. Smyth, and N. J. O’Higgins, “Premorphological Metabolic Changes in Human Breast Carcinogenesis,” British Journal of Sur-gery, Vol. 77, No. 10, 1990, pp. 1179-1182. doi:10.1002/bjs.1800771029
[51] [51] R. Dutu, M. Nedelea, G. Veluda and V. Burculet, “Cy-toenzymologic Investigations on Carcinomas of the Cer-vix Uteri,” Acta Cytologica, Vol. 24, No. 2, 1980, pp. 160-166.
[52] [52] K. Ikezaki, K. L. Black, S. G. Conklin, and D. P. Becker, “Histochemical Evaluation of Energy Metabolism in Rat Glioma,” Neurological Research, Vol. 14, No. 4, 1992, pp. 289-293.
[53] [53] R. J. DeBerardinis, et al., “Beyond Aerobic Glycolysis: Transformed Cells can Engage in Glutamine Metabolism that Exceeds the Requirement for Protein and Nucleotide Synthesis,” Proceedings of the National Academy of Sci-ences of the USA, Vol. 104, No. 49, 2007, pp. 19345-19350. doi:10.1073/pnas.0709747104
[54] [54] F. P. Kuhajda, et al., “Fatty Acid Synthesis: A Potential Selective Target for Antineoplastic Therapy,” Proceed-ings of the National Academy of Sciences of the USA, Vol. 91, No. 14, 1994, pp. 6379-6383. doi:10.1073/pnas.91.14.6379
[55] [55] C. Pompeia, et al., “Effect of Fatty Acids on Leukocyte Function,” Brazilian Journal of Medical and Biological Research, Vol. 33, No. 11, 2000, pp. 1255-1268. doi:10.1590/S0100-879X2000001100001
[56] [56] N. F. Boyd, M. Cousins, G. Lockwood and D. Tritchler, “Dietary Fat and Breast Cancer Risk: The Feasibility of a Clinical Trial of Breast Cancer Prevention,” Lipids, Vol. 27, No. 10, 1992, pp. 821-826. doi:10.1007/BF02535857
[57] [57] H. A. Risch, M. Jain, L. D. Marrett and G. R. Howe, “Dietary Fat Intake and Risk of Epithelial Ovarian Can-cer,” Journal of the National Cancer Institute, Vol. 86, No. 18, 1994, pp. 1409-1415. doi:10.1093/jnci/86.18.1409
[58] [58] H. A. Risch, L. D. Marrett, M. Jain, and G. R. Howe, “Differences in Risk Factors for Epithelial Ovarian Can-cer by Histologic Type. Results of a Case-Control Study,” American Journal of Epidemiology, Vol. 144, No. 4, 1996, pp. 363-372.
[59] [59] K. K. Carroll, “Dietary Fat and Breast Cancer,” Lipids, Vol. 27, No. 10, 1992, pp. 793-797. doi:10.1007/BF02535852
[60] [60] B. S. Reddy, “Dietary Fat and Colon Cancer: Animal Model Studies,” Lipids, Vol. 27, No. 10, 1992, pp. 807-813. doi:10.1007/BF02535855
[61] [61] B. J. Thompson and S. Smith, “Biosynthesis of Fatty Acids by Lactating Human Breast Epithelial Cells: An Evaluation of the Contribution to the Overall Composi-tion of Human Milk Fat,” Pediatric Research, Vol. 19, No. 1, 1985, pp. 139-143. doi:10.1203/00006450-198501000-00036
[62] [62] H. S. Sul and D. Wang, “Nutritional and Hormonal Regulation of Enzymes in Fat Synthesis: Studies of Fatty Acid Synthase and Mitochondrial Glycerol-3-Phosphate Acyltransferase Gene Transcription,” Annual Review of Nutrition, Vol. 18, 1998, pp. 331-351. doi:10.1146/annurev.nutr.18.1.331
[63] [63] G. Medes, A. Thomas and S. Weinhouse, “Metabolism of Neoplastic Tissue. IV. A Study of Lipid Synthesis in Neoplastic Tissue Slices in Vitro,” Cancer Research, Vol. 13, No. 1, 1953, pp. 27-29.
[64] [64] L. Z. Milgraum, L. A. Witters, G. R. Pasternack and F. P. Kuhajda, “Enzymes of the Fatty Acid Synthesis Pathway Are Highly Expressed in Situ Breast Carcinoma,” Clini-cal Cancer Research, Vol. 3, No. 11, 1997, pp. 2115-2120.
[65] [65] P. L. Alo, et al., “Expression of Fatty Acid Synthase (Fas) as a Predictor of Recurrence in Stage 1 Breast Carcinoma Patients,” Cancer, Vol. 77, No. 3, 1996, pp. 474-482. doi:10.1002/(SICI)1097-0142(19960201)77:3<474::AID-CNCR8>3.0.CO;2-K
[66] [66] A. Rashid, et al., “Elevated Expression of Fatty Acid Synthase and Fatty Acid Synthetic Activity in Colorectal Neoplasia,” American Journal of Pathology, Vol. 150, No. 1, 1997, pp. 201-208.
[67] [67] P. L. Alo, et al., “Fatty Acid Synthase (Fas) Predictive Strength in Poorly Differentiated Early Breast Carcino-mas,” Tumori, Vol. 85, No. 1, 1999, pp. 35-40.
[68] [68] J. I. Epstein, M. Carmichael and A. W. Partin, “Oa-519 (Fatty Acid Synthase) as an Independent Predictor of Pathologic State in Adenocarcinoma of the Prostate,” Urology, Vol. 45, No. 1, 1995, pp. 81-86. doi:10.1016/S0090-4295(95)96904-7
[69] [69] T. S. Gansler, W. Hardman, D. A. Hunt, S. Schaffel and R. A. Hennigar, “Increased Expression of Fatty Acid Synthase (Oa-519) in Ovarian Neoplasms Predicts Shorter Survival,” Human Pathology, Vol. 28, No. 6, 1997, pp. 686-692. doi:10.1016/S0046-8177(97)90177-5
[70] [70] E. S. Pizer, S. F. Lax, F. P. Kuhajda, G. R. Pasternack and R. J. Kurman, “Fatty Acid Synthase Expression in Endo-metrial Carcinoma: Correlation with Cell Proliferation and Hormone Receptors,” Cancer, Vol. 83, No. 3, 1998, pp. 528-537. doi:10.1002/(SICI)1097-0142(19980801)83:3<528::AID-CNCR22>3.0.CO;2-X
[71] [71] M. S. Shurbaji, J. H. Kalbfleisch and T. S. Thurmond, “Immunohistochemical Detection of a Fatty Acid Syn-thase (Oa-519) as a Predictor of Progression of Prostate Cancer,” Human Pathology, Vol. 27, No. 9, 1996, pp. 917-921. doi:10.1016/S0046-8177(96)90218-X
[72] [72] F. P. Kuhajda, “Fatty-Acid Synthase and Human Cancer: New Perspectives on Its Role in Tumor Biology,” Nutri-tion, Vol. 16, No. 3, 2000, pp. 202-208. doi:10.1016/S0899-9007(99)00266-X
[73] [73] J. A. Menendez and R. Lupu, “Fatty Acid Synthase and the Lipogenic Phenotype in Cancer Pathogenesis,” Nature Reviews Cancer, Vol. 7, No. 10, 2007, pp. 763-777. doi:10.1038/nrc2222
[74] [74] M. Ookhtens, R. Kannan, I. Lyon and N. Baker, “Liver and Adipose Tissue Contributions to Newly Formed Fatty Acids in an Ascites Tumor,” American Journal of Physi-ology, Vol. 247, No. 1, Pt 2, 1984, pp. R146-R153.
[75] [75] E. Kalkhoven, L. Kwakkenbos-Isbrucker, S. W. de Laat, P. T. van der Saag and B. van der Burg, “Synthetic Pro-gestins Induce Proliferation of Breast Tumor Cell Lines via the Progesterone or Estrogen Receptor,” Molecular and Cellular Endocrinology, Vol. 102, No. 1-2, 1994, pp. 45-52. doi:10.1016/0303-7207(94)90096-5
[76] [76] C. Kumar-Sinha, K. W. Ignatoski, M. E. Lippman, S. P. Ethier and A. M. Chinnaiyan, “Transcriptome Analysis of Her2 Reveals a Molecular Connection to Fatty Acid Syn-thesis,” Cancer Research, Vol. 63, No. 1, 2003, pp. 132-139.
[77] [77] Y. Chang, J. Wang, X. Lu, D. P. Thewke and R. J. Mason, “Kgf Induces Lipogenic Genes through a Pi3k and Jnk/Srebp-1 Pathway in H292 Cells,” Journal of Lipid Research, Vol. 46, No. 12, 2005, pp. 2624-2635. doi:10.1194/jlr.M500154-JLR200
[78] [78] J. V. Swinnen, et al., “Stimulation of Tumor-Associated Fatty Acid Synthase Expression by Growth Factor Acti-vation of the Sterol Regulatory Element-Binding Protein Pathway,” Oncogene, Vol. 19, No. 45, 2000, pp. 5173-5181. doi:10.1038/sj.onc.1203889
[79] [79] H. Pelicano, et al., “Mitochondrial Respiration Defects in Cancer Cells Cause Activation of Akt Survival Pathway through a Redox-Mediated Mechanism,” Journal of Cell Biology, Vol. 175, No. 6, 2006, pp. 913-923. doi:10.1083/jcb.200512100
[80] [80] S. Bandyopadhyay, et al., “Fas Expression Inversely Correlates with Pten Level in Prostate Cancer and a Pi 3-Kinase Inhibitor Synergizes with Fas Sirna to Induce Apoptosis,” Oncogene, Vol. 24, No. 34, 2005, pp. 5389-5395. doi:10.1038/sj.onc.1208555
[81] [81] A. M. D'Erchia, A. Tullo, K. Lefkimmiatis, C. Saccone and E. Sbisa, “The Fatty Acid Synthase Gene is a Con-served P53 Family Target from Worm to Human,” Cell Cycle, Vol. 5, No. 7, 2006, pp. 750-758. doi:10.4161/cc.5.7.2622
[82] [82] T. Porstmann, et al., “Pkb/Akt Induces Transcription of Enzymes Involved in Cholesterol and Fatty Acid Biosyn-thesis Via Activation of Srebp,” Oncogene, Vol. 24, No. 43, 2005, pp. 6465-6481.
[83] [83] E. Furuta, et al., “Fatty Acid Synthase Gene is up-Regulated by Hypoxia Via Activation of Akt and Sterol Regulatory Element Binding Protein-1,” Cancer Research, Vol. 68, No. 4, 2008, pp. 1003-1011. doi:10.1158/0008-5472.CAN-07-2489
[84] [84] M. A. Hediger and D. B. Rhoads, “Molecular Physiology of Sodium-Glucose Cotransporters,” Physiological Re-views, Vol. 74, No. 4, 1994, pp. 993-1026.
[85] [85] A. Carruthers, “Facilitated Diffusion of Glucose,” Physiological Reviews, Vol. 70, No. 4, 1990, pp. 1135-1176.
[86] [86] M. L. Macheda, S. Rogers and J. D. Best, “Molecular and Cellular Regulation of Glucose Transporter (Glut) Pro-teins in Cancer,” Journal of Cellular Physiology, Vol. 202, No. 3, 2005, pp. 654-662. doi:10.1002/jcp.20166
[87] [87] C. Postic, et al., “Development and Regulation of Glu-cose Transporter and Hexokinase Expression in Rat,” American Journal of Physiology, Vol. 266, No. 4, Pt 1, 1994, pp. E548-E559.
[88] [88] T. Santalucia, et al., “Developmental Regulation of Glut-1 (Erythroid/Hep G2) and Glut-4 (Muscle/Fat) Glu-cose Transporter Expression in Rat Heart, Skeletal Mus-cle, and Brown Adipose Tissue,” Endocrinology, Vol. 130, No. 2, 1992, pp. 837-846. doi:10.1210/en.130.2.837
[89] [89] M. Mueckler, et al., “Sequence and Structure of a Human Glucose Transporter,” Science, Vol. 229, No. 4717, 1985, pp. 941-945. doi:10.1126/science.3839598
[90] [90] M. J. Birnbaum, H. C. Haspel, and O. M. Rosen, “Clon-ing and Characterization of a Cdna Encoding the Rat Brain Glucose-Transporter Protein,” Proceedings of the National Academy of Sciences of the USA, Vol. 83, No. 16, 1986, pp. 5784-5788. doi:10.1073/pnas.83.16.5784
[91] [91] H. Fukumoto, S. Seino, H. Imura, Y. Seino and G. I. Bell, “Characterization and Expression of Human Hepg2/ Erythrocyte Glucose-Transporter Gene,” Diabetes, Vol. 37, No. 5, 1988, pp. 657-661. doi:10.2337/diabetes.37.5.657
[92] [92] B. Thorens, H. K. Sarkar, H. R. Kaback and H. F. Lodish, “Cloning and Functional Expression in Bacteria of a Novel Glucose Transporter Present in Liver, Intestine, Kidney, and Beta-Pancreatic Islet Cells,” Cell, Vol. 55, No. 2, 1988, pp. 281-290. doi:10.1016/0092-8674(88)90051-7
[93] [93] T. Kayano, et al., “Evidence for a Family of Human Glu-cose Transporter-Like Proteins. Sequence and Gene Lo-calization of a Protein Expressed in Fetal Skeletal Muscle and Other Tissues,” Journal of Biological Chemistry, Vol. 263, No. 30, 1988, pp. 15245-15248.
[94] [94] M. J. Birnbaum, “Identification of a Novel Gene Encod-ing an Insulin-Responsive Glucose Transporter Protein,” Cell, Vol. 57, No. 2, 1989, pp. 305-315. doi:10.1016/0092-8674(89)90968-9
[95] [95] T. Kayano, et al., “Human Facilitative Glucose Trans-porters. Isolation, Functional Characterization, and Gene Localization of Cdnas Encoding an Isoform (Glut5) Ex-pressed in Small Intestine, Kidney, Muscle, and Adipose Tissue and an Unusual Glucose Transporter Pseu-dogene-Like Sequence (Glut6),” Journal of Biological Chemistry, Vol. 265, No. 22, 1990, pp. 13276-13282.
[96] [96] C. F. Burant, J. Takeda, E. Brot-Laroche, G. I. Bell and N. O. Davidson, “Fructose Transporter in Human Sper-matozoa and Small Intestine Is Glut5,” Journal of Bio-logical Chemistry, Vol. 267, No. 21, 1992, pp. 14523-14526.
[97] [97] M. E. Phelps, “Pet: The Merging of Biology and Imaging into Molecular Imaging,” Journal of Nuclear Medicine, Vol. 41, No. 4, 2000, pp. 661-681.
[98] [98] T. A. Smith, “Mammalian Hexokinases and Their Ab-normal Expression in Cancer,” British Journal of Bio-medical Science, Vol. 57, No. 2, 2000, pp. 170-178.
[99] [99] E. K. Pauwels, E. J. Sturm, E. Bombardieri, F. J. Cleton and M. P. Stokkel, “Positron-Emission Tomography with [18f] Fluorodeoxyglucose. Part 1. Biochemical Uptake Mechanism and Its Implication for Clinical Studies,” Journal of Cancer Research and Clinical Oncology, Vol. 126, No. 10, 2000, pp. 549-559. doi:10.1007/PL00008465
[100] [100] M. J. Birnbaum, H. C. Haspel and O. M. Rosen, “Trans-formation of Rat Fibroblasts by Fsv Rapidly Increases Glucose Transporter Gene Transcription,” Science, Vol. 235, No. 4795, 1987, pp. 1495-1498.
[101] doi:10.1126/science.3029870 [101] J. S. Flier, M. M. Mueckler, P. Usher and H. F. Lodish, “Elevated Levels of Glucose Transport and Transporter Messenger Rna Are Induced by Ras or Src Oncogenes,” Science, Vol. 235, No. 4795, 1987, pp. 1492-1495. doi:10.1126/science.3103217
[102] [102] T. Murakami, et al., “Identification of Two Enhancer Elements in the Gene Encoding the Type 1 Glucose Transporter from the Mouse Which are Responsive to Serum, Growth Factor, and Oncogenes,” Journal of Bio-logical Chemistry, Vol. 267, No. 13, 1992, pp. 9300-9306.
[103] [103] T. C. Yen, et al., “18f-Fdg Uptake in Squamous Cell Carcinoma of the Cervix is Correlated with Glucose Transporter 1 Expression,” Journal of Nuclear Medicine, Vol. 45, No. 1, 2004, pp. 22-29.
[104] [104] R. Bos, et al., “Biologic Correlates of (18) Fluorodeo- xyglucose Uptake in Human Breast Cancer Measured by Positron Emission Tomography,” Journal of Clinical Oncology, Vol. 20, No. 2, 2002, pp. 379-387. doi:10.1200/JCO.20.2.379
[105] [105] K. Higashi, et al., “Correlation of Glut-1 Glucose Trans-porter Expression With,” European Journal of Nuclear Medicine, Vol. 27, No. 12, 2000, pp. 1778-1785. doi:10.1007/s002590000367
[106] [106] T. Kurokawa, et al., “Expression of Glut-1 Glucose Transfer, Cellular Proliferation Activity and Grade of Tumor Correlate with [F-18]-Fluorodeoxyglucose Uptake by Positron Emission Tomography in Epithelial Tumors of the Ovary,” International Journal of Cancer, Vol. 109, No. 6, 2004, pp. 926-932. doi:10.1002/ijc.20057
[107] [107] R. P. Beaney, “Positron Emission Tomography in the Study of Human Tumors,” Seminars in Nuclear Medicine, Vol. 14, No. 4, 1984, pp. 324-341. doi:10.1016/S0001-2998(84)80006-9
[108] [108] G. Di Chiro, et al., “Glucose Utilization of Cerebral Gliomas Measured by [18f] Fluorodeoxyglucose and Positron Emission Tomography,” Neurology, Vol. 32, No. 12, 1982, pp. 1323-1329.
[109] [109] R. E. Airley and A. Mobasheri, “Hypoxic Regulation of Glucose Transport, Anaerobic Metabolism and Angio-genesis in Cancer: Novel Pathways and Targets for Anti-cancer Therapeutics,” Chemotherapy, Vol. 53, No. 4, 2007, pp. 233-256. doi:10.1159/000104457
[110] [110] C. Rudlowski, et al., “Glut1 Messenger Rna and Protein Induction Relates to the Malignant Transformation of Cervical Cancer,” American Journal of Clinical Pathol-ogy Vol. 120, No. 5, 2003, pp. 691-698. doi:10.1309/4KYNQM5862JW2GD7
[111] [111] M. Younes, R. W. Brown, D. R. Mody, L. Fernandez and R. Laucirica, “Glut1 Expression in Human Breast Carci-noma: Correlation with Known Prognostic Markers,” Anticancer Research, Vol. 15, No. 6B, 1995, pp. 2895-2898.
[112] [112] G. Cantuaria, et al., “Glut-1 Expression in Ovarian Car-cinoma: Association with Survival and Response to Chemotherapy,” Cancer, Vol. 92, No. 5, 2001, pp. 1144-1150. doi:10.1002/1097-0142(20010901)92:5<1144::AID-CNCR1432>3.0.CO;2-T
[113] [113] S. C. Baer, L. Casaubon and M. Younes, “Expression of the Human Erythrocyte Glucose Transporter Glut1 in Cutaneous Neoplasia,” Journal of the American Academy of Dermatology, Vol. 37, No. 4, 1997, pp. 575-577. doi:10.1016/S0190-9622(97)70174-9
[114] [114] S. S. Kang, et al., “Clinical Significance of Glucose Transporter 1 (Glut1) Expression in Human Breast Car-cinoma,” Japanese Journal of Cancer Research, Vol. 93, No. 10, 2002, pp. 1123-1128.
[115] [115] M. Younes, L. V. Lechago, J. R. Somoano, M. Mosharaf, and J. Lechago, “Immunohistochemical Detection of Glut3 in Human Tumors and Normal Tissues,” Antican-cer Research, Vol. 17, No. 4A, 1997, pp. 2747-2750.
[116] [116] S. P. Zamora-Leon, et al., “Expression of the Fructose Transporter Glut5 in Human Breast Cancer,” Proceedings of the National Academy of Sciences of the USA, Vol. 93, No. 5, 1996, pp. 1847-1852. doi:10.1073/pnas.93.5.1847
[117] [117] C. Binder, L. Binder, D. Marx, A. Schauer, and W. Hid-demann, “Deregulated Simultaneous Expression of Mul-tiple Glucose Transporter Isoforms in Malignant Cells and Tissues,” Anticancer Research, Vol. 17, No. 6D, 1997, pp. 4299-4304.
[118] [118] R. S. Brown and R. L. Wahl, “Overexpression of Glut-1 Glucose Transporter in Human Breast Cancer. An Im-munohistochemical Study,” Cancer, Vol. 72, No. 10, 1993, pp. 2979-2985. doi:10.1002/1097-0142(19931115)72:10<2979::AID-CNCR2820721020>3.0.CO;2-X
[119] [119] A. Godoy, et al., “Differential Subcellular Distribution of Glucose Transporters Glut1-6 and Glut9 in Human Can-cer: Ultrastructural Localization of Glut1 and Glut5 in Breast Tumor Tissues,” Journal of Cellular Physiology, Vol. 207, No. 3, 2006, pp. 614-627. doi:10.1002/jcp.20606
[120] [120] P. L. Alo, et al., “Immunohistochemical Expression of Human Erythrocyte Glucose Transporter and Fatty Acid Synthase in Infiltrating Breast Carcinomas and Adjacent Typical/Atypical Hyperplastic or Normal Breast Tissue,” American Journal of Clinical Pathology, Vol. 116, No. 1, 2001, pp. 129-134. doi:10.1309/5Y2L-CDCK-YB55-KDK6
[121] [121] M. Grover-McKay, S. A. Walsh, E. A. Seftor, P. A. Thomas and M. J. Hendrix, “Role for Glucose Trans-porter 1 Protein in Human Breast Cancer,” Pathology & Oncology Research, Vol. 4, No. 2, 1998, pp. 115-120. doi:10.1007/BF02904704
[122] [122] A. M. Meneses, et al., “Regulation of Glut3 and Glucose Uptake by the Camp Signalling Pathway in the Breast Cancer Cell Line Zr-75,” Journal of Cellular Physiology, Vol. 214, No. 1, 2008, pp. 110-116. doi:10.1002/jcp.21166
[123] [123] S. Rogers, S. E. Docherty, J. L. Slavin, M. A. Henderson, and J. D. Best, “Differential Expression of Glut12 in Breast Cancer and Normal Breast Tissue,” Cancer Letters, Vol. 193, No. 2, 2003, pp. 225-233. doi:10.1016/S0304-3835(03)00010-7
[124] [124] S. Rogers, et al., “Identification of a Novel Glucose Transporter-Like Protein-Glut-12,” American Journal of Physiology-Endocrinology and Metabolism, Vol. 282, No. 3, 2002, pp. E733-E738.
[125] [125] G. L. Semenza, “Targeting Hif-1 for Cancer Therapy,” Nature Reviews Cancer, Vol. 3, No. 10, 2003, pp. 721-732. doi:10.1038/nrc1187
[126] [126] R. A. Gatenby, et al., “Cellular Adaptations to Hypoxia and Acidosis During Somatic Evolution of Breast Can-cer,” British Journal of Cancer, Vol. 97, No. 5, 2007, pp. 646-653. doi:10.1038/sj.bjc.6603922
[127] [127] J. Li, et al., “Knockdown of Hypoxia-Inducible Fac-tor-1alpha in Breast Carcinoma Mcf-7 Cells Results in Reduced Tumor Growth and Increased Sensitivity to Methotrexate,” Biochemical and Biophysical Research Communications, Vol. 342, No. 4, 2006, pp. 1341-1351. doi:10.1016/j.bbrc.2006.02.094
[128] [128] P. Burgman, J. A. Odonoghue, J. L. Humm and C. C. Ling, “Hypoxia-Induced Increase in Fdg Uptake in Mcf7 Cells,” Journal of Nuclear Medicine, Vol. 42, No. 1, 2001, pp. 170-175.
[129] [129] S. L. Pankratz, E. Y. Tan, Y. Fine, A. M. Mercurio and L. M. Shaw, “Insulin Receptor Substrate-2 Regulates Aero-bic Glycolysis in Mouse Mammary Tumor Cells Via Glucose Transporter 1,” Journal of Biological Chemistry, Vol. 284, No. 4, 2009, pp. 2031-2037. doi:10.1074/jbc.M804776200
[130] [130] A. Barthel, et al., “Regulation of Glut1 Gene Transcrip-tion by the Serine/Threonine Kinase Akt1,” Journal of Biological Chemistry, Vol. 274, No. 29, 1999, pp. 20281-20286. doi:10.1074/jbc.274.29.20281
[131] [131] R. C. Osthus, et al., “Deregulation of Glucose Transporter 1 and Glycolytic Gene Expression by C-Myc,” Journal of Biological Chemistry, Vol. 275, No. 29, 2000, pp. 21797-21800. doi:10.1074/jbc.C000023200
[132] [132] J. C. Rathmell, et al., “Akt-Directed Glucose Metabolism Can Prevent Bax Conformation Change and Promote Growth Factor-Independent Survival,” Molecular and Cellular Biology, Vol. 23, No. 20, 2003, pp. 7315-7328. doi:10.1128/MCB.23.20.7315-7328.2003
[133] [133] D. Rivenzon-Segal, S. Boldin-Adamsky, D. Seger, R. Seger, and H. Degani, “Glycolysis and Glucose Trans-porter 1 as Markers of Response to Hormonal Therapy in Breast Cancer,” International Journal of Cancer, Vol. 107, No. 2, 2003, pp. 177-182. doi:10.1002/ijc.11387
[134] [134] M. Neeman and H. Degani, “Metabolic Studies of Estro-gen and Tamoxifen-Treated Human Breast Cancer Cells by Nuclear Magnetic Resonance Spectroscopy,” Cancer Research, Vol. 49, No. 3, 1989, pp. 589-594.
[135] [135] P. Laudanski, et al., “Expression of Glucose Transporter Glut-1 and Estrogen Receptors Er-Alpha and Er-Beta in Human Breast Cancer,” Neoplasma, Vol. 51, No. 3, 2004, pp. 164-168.
[136] [136] G. Wilding, M. E. Lippman and E. P. Gelmann, “Effects of Steroid Hormones and Peptide Growth Factors on Protooncogene C-Fos Expression in Human Breast Can-cer Cells,” Cancer Research, Vol. 48, No. 4, 1988, pp. 802-805.
[137] [137] M. Guppy, P. Leedman, X. Zu and V. Russell, “Contribu-tion by Different Fuels and Metabolic Pathways to the Total Atp Turnover of Proliferating Mcf-7 Breast Cancer Cells,” Biochemical Journal, Vol. 364, Pt 1, 2002, pp. 309-315.
[138] [138] R. Moreno-Sanchez, S. Rodriguez-Enriquez, A. Marin- Hernandez and E. Saavedra, “Energy Metabolism in Tu-mor Cells,” Febs Journal, Vol. 274, No. 6, 2007, pp. 1393-1418. doi:10.1111/j.1742-4658.2007.05686.x
[139] [139] S. Rodriguez-Enriquez, et al., “Control of Cellular Prolif-eration by Modulation of Oxidative Phosphorylation in Human and Rodent Fast-Growing Tumor Cells,” Toxi-cology and Applied Pharmacology, Vol. 215, No. 2, 2006, pp. 208-217. doi:10.1016/j.taap.2006.02.005
[140] [140] R. Diaz-Ruiz, S. Uribe-Carvajal, A. Devin and M. Rig-oulet, “Tumor Cell Energy Metabolism and Its Common Features with Yeast Metabolism,” Biochimica et Bio-physica Acta, Vol. 1796, No. 2, 2009, pp. 252-265.
[141] [141] H. Pelicano, D. S. Martin, R. H. Xu and P. Huang, “Gly-colysis Inhibition for Anticancer Treatment,” Oncogene, Vol. 25, No. 34, 2006, pp. 4633-4646. doi:10.1038/sj.onc.1209597
[142] [142] D. Singh, et al., “Optimizing Cancer Radiotherapy with 2-Deoxy-D-Glucose Dose Escalation Studies in Patients with Glioblastoma Multiforme,” Strahlentherapie und Onkologie, Vol. 181, No. 8, 2005, pp. 507-514. doi:10.1007/s00066-005-1320-z
[143] [143] C. W. Christopher, W. W. Colby and D. Ullrey, “Derep-ression and Carrier Turnover: Evidence for Two Distinct Mechanisms of Hexose Transport Regulation in Animal Cells,” Journal of Cellular Physiology, Vol. 89, No. 4, 1976, pp. 683-692. doi:10.1002/jcp.1040890427
[144] [144] R. Keller, “Suppression of Natural Antitumour Defence Mechanisms by Phorbol Esters,” Nature, Vol. 282, No. 5740, 1979, pp. 729-731. doi:10.1038/282729a0
[145] [145] E. M. Bessell, V. D. Courtenay, A. B. Foster, M. Jones, and J. H. Westwood, “Some in Vivo and in Vitro Anti-tumour Effects of the Deoxyfluoro-D-Glucopyranoses,” European Journal of Cancer, Vol. 9, No. 7, 1973, pp. 463-470. doi:10.1016/0014-2964(73)90128-X
[146] [146] J. H. Risse, et al., “18f-Fdg-Pet and Histopathology in 131i-Lipiodol Treatment for Primary Liver Cancer,” Cancer Biotherapy & Radiopharmaceuticals, Vol. 24, No. 4, 2009, pp. 445-452. doi:10.1089/cbr.2008.0560
[147] [147] M. Kurtoglu, J. C. Maher and T. J. Lampidis, “Differen-tial Toxic Mechanisms of 2-Deoxy-D-Glucose Versus 2-Fluorodeoxy-D-Glucose in Hypoxic and Normoxic Tumor Cells,” Antioxidants and Redox Signaling, Vol. 9, No. 9, 2007, pp. 1383-1390. doi:10.1089/ars.2007.1714
[148] [148] I. F. Tannock, P. Guttman and A. M. Rauth, “Failure of 2-Deoxy-D-Glucose and 5-Thio-D-Glucose to Kill Hy-poxic Cells of Two Murine Tumors,” Cancer Research, Vol. 43, No. 3, 1983, pp. 980-983.
[149] [149] J. H. Kim, S. H. Kim, E. W. Hahn and C. W. Song, “5-Thio-D-Glucose Selectively Potentiates Hyperthermic Killing of Hypoxic Tumor Cells,” Science, Vol. 200, No. 4338, 1978, pp. 206-207. doi:10.1126/science.635582
[150] [150] E. M. Bessell, A. B. Foster and J. H. Westwood, “The Use of Deoxyfluoro-D-Glucopyranoses and Related Compounds in a Study of Yeast Hexokinase Specificity,” Biochemical Journal, Vol. 128, No. 2, 1972, pp. 199-204.
[151] [151] T. J. Lampidis, et al., “Efficacy of 2-Halogen Substituted D-Glucose Analogs in Blocking Glycolysis and Killing ‘Hypoxic Tumor Cells’,” Cancer Chemotherapy and Pharmacology, Vol. 58, No. 6, 2006, pp. 725-734. doi:10.1007/s00280-006-0207-8
[152] [152] E. L. Coe and R. C. Strunk, “The Effect of Oxamate on Glycolysis in Intact Ascites Tumor Cells. 1. Kinetic Evi-dence for a Dual Glycolytic System,” Biochimica et Bio-physica Acta, Vol. 208, No. 2, 1970, pp. 189-202.
[153] [153] S. Bonnet, et al., “A Mitochondria-K+ Channel Axis is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth,” Cancer Cell, Vol. 11, No. 1, 2007, pp. 37-51. doi:10.1016/j.ccr.2006.10.020
[154] [154] J. Y. Wong, G. S. Huggins, M. Debidda, N. C. Munshi, and I. De Vivo, “Dichloroacetate Induces Apoptosis in Endometrial Cancer Cells,” Gynecologic Oncology, Vol. 109, No. 3, 2008, pp. 394-402. doi:10.1016/j.ygyno.2008.01.038
[155] [155] T. J. Lampidis, S. D. Bernal, I. C. Summerhayes and L. B. Chen, “Selective Toxicity of Rhodamine 123 in Carci-noma Cells in Vitro,” Cancer Research, Vol. 43, No. 2, 1983, pp. 716-720.
[156] [156] S. D. Bernal, T. J. Lampidis, R. M. McIsaac and L. B. Chen, “Anticarcinoma Activity in Vivo of Rhodamine 123, a Mitochondrial-Specific Dye,” Science, Vol. 222, No. 4620, 1983, pp. 169-172. doi:10.1126/science.6623064
[157] [157] R. M. Sutherland, “Cell and Environment Interactions in Tumor Microregions: The Multicell Spheroid Model,” Science, Vol. 240, No. 4849, 1988, pp. 177-184. doi:10.1126/science.2451290
[158] [158] L. Galluzzi, N. Larochette, N. Zamzami and G. Kroemer, “Mitochondria as Therapeutic Targets for Cancer Che-motherapy,” Oncogene, Vol. 25, No. 34, 2006, pp. 4812-4830. doi:10.1038/sj.onc.1209598
[159] [159] C. E. Griguer, et al., “Pharmacologic Manipulations of Mitochondrial Membrane Potential (Deltapsim) Selec-tively in Glioma Cells,” Journal of Neuro-Oncology, Vol. 81, No. 1, 2007, pp. 9-20. doi:10.1007/s11060-006-9201-6
[160] [160] G. J. Arismendi-Morillo and A. V. Castellano-Ramirez, “Ultrastructural Mitochondrial Pathology in Human As-trocytic Tumors: Potentials Implications Pro-therapeutics Strategies,” Journal of Electron Microscopy (Tokyo), Vol. 57, No. 1, 2008, pp. 33-39. doi:10.1093/jmicro/dfm038
[161] [161] Z. Chen, W. Lu, C. Garcia-Prieto and P. Huang, “The Warburg Effect and Its Cancer Therapeutic Implications,” Journal of Bioenergetics and Biomembranes, Vol. 39, No. 3, 2007, pp. 267-274. doi:10.1007/s10863-007-9086-x
[162] [162] C. W. Yeh, W. J. Chen, C. T. Chiang, S. Y. Lin-Shiau, and J.K. Lin, “Suppression of Fatty Acid Synthase in Mcf-7 Breast Cancer Cells by Tea and Tea Polyphenols: A Possible Mechanism for Their Hypolipidemic Effects,” The Pharmacogenomics Journal, Vol. 3, No. 5, 2003, pp. 267-276.
[163] [163] C. T. Chiang, T. D. Way, S. J. Tsai and J. K. Lin, “Dios-genin, a Naturally Occurring Steroid, Suppresses Fatty Acid Synthase Expression in Her2-Overexpressing Breast Cancer Cells through Modulating Akt, Mtor and Jnk Phosphorylation,” Febs Letters, Vol. 581, No. 30, 2007, pp. 5735-5742. doi:10.1016/j.febslet.2007.11.021
[164] [164] J. S. Lee, M. S. Lee, W. K. Oh and J. Y. Sul, “Fatty Acid Synthase Inhibition by Amentoflavone Induces Apoptosis and Antiproliferation in Human Breast Cancer Cells,” Biological & Pharmaceutical Bulletin, Vol. 32, No. 8, 2009, pp. 1427-1432. doi:10.1248/bpb.32.1427
[165] [165] C. Yan, et al., “A New Targeting Approach for Breast Cancer Gene Therapy Using the Human Fatty Acid Syn-thase Promoter,” Acta Oncologica, Vol. 46, No. 6, 2007, pp. 773-781. doi:10.1080/02841860601016070
[166] [166] R. Lupu and J. A. Menendez, “Targeting Fatty Acid Syn-thase in Breast and Endometrial Cancer: An Alternative to Selective Estrogen Receptor Modulators?” Endocri-nology, Vol. 147, No. 9, 2006, pp. 4056-4066. doi:10.1210/en.2006-0486
[167] [167] A. Vazquez-Martin, S. Ropero, J. Brunet, R. Colomer and J. A. Menendez, “Inhibition of Fatty Acid Synthase (Fasn) Synergistically Enhances the Efficacy of 5-Fluoro- uracil in Breast Carcinoma Cells,” Oncology Reports, Vol. 18, No. 4, 2007, pp. 973-980.
[168] [168] H. Liu, Y. Liu and J. T. Zhang, “A New Mechanism of Drug Resistance in Breast Cancer Cells: Fatty Acid Syn-thase Overexpression-Mediated Palmitate Overproduc-tion,” Molecular Cancer Therapeutics, Vol. 7, No. 2, 2008, pp. 263-270. doi:10.1158/1535-7163.MCT-07-0445
[169] [169] S. Bandyopadhyay, et al., “Mechanism of Apoptosis In-duced by the Inhibition of Fatty Acid Synthase in Breast Cancer Cells,” Cancer Research, Vol. 66, No. 11, 2006, pp. 5934-5940. doi:10.1158/0008-5472.CAN-05-3197
[170] [170] D. Manka, Z. Spicer and D. E. Millhorn, “Bcl-2/Adeno- virus E1b 19 Kda Interacting Protein-3 Knockdown En- ables Growth of Breast Cancer Metastases in the Lung, Liver, and Bone,” Cancer Research, Vol. 65, No. 24, 2005, pp. 11689-11693. doi:10.1158/0008-5472.CAN-05-3091
[171] [171] X. Liu, Y. Shi, V. L. Giranda and Y. Luo, “Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway Sensitizes Mda-Mb468 Human Breast Cancer Cells to Ceru-lenin-Induced Apoptosis,” Molecular Cancer Therapeu-tics, Vol. 5, No. 3, 2006, pp. 494-501. doi:10.1158/1535-7163.MCT-05-0049
[172] [172] V. Chajes, M. Cambot, K. Moreau, G. M. Lenoir and V. Joulin, “Acetyl-Coa Carboxylase Alpha is Essential to Breast Cancer Cell Survival,” Cancer Research, Vol. 66, No. 10, 2006, pp. 5287-5294. doi:10.1158/0008-5472.CAN-05-1489
[173] [173] J. N. Thupari, M. L. Pinn and F. P. Kuhajda, “Fatty Acid Synthase Inhibition in Human Breast Cancer Cells Leads to Malonyl-Coa-Induced Inhibition of Fatty Acid Oxida-tion and Cytotoxicity,” Biochemical and Biophysical Re-search Communications, Vol. 285, No. 2, 2001, pp. 217-223. doi:10.1006/bbrc.2001.5146
[174] [174] D. Rivenzon-Segal, E. Rushkin, S. Polak-Charcon and H. Degani, “Glucose Transporters and Transport Kinetics in Retinoic Acid-Differentiated T47d Human Breast Cancer Cells,” American Journal of Physiology-Endocrinology and Metabolism, Vol. 279, No. 3, 2000, pp. E508-E519.
[175] [175] S. Rastogi, S. Banerjee, S. Chellappan and G. R. Simon, “Glut-1 Antibodies Induce Growth Arrest and Apoptosis in Human Cancer Cell Lines,” Cancer Letters, Vol. 257, No. 2, 2007, pp. 244-251. doi:10.1016/j.canlet.2007.07.021
[176] [176] X. Cao, et al., “Glucose Uptake Inhibitor Sensitizes Can-cer Cells to Daunorubicin and Overcomes Drug Resis-tance in Hypoxia,” Cancer Chemotherapy and Pharma-cology, Vol. 59, No. 4, 2007, pp. 495-505. doi:10.1007/s00280-006-0291-9
[177] [177] K. K. Chan, J. Y. Chan, K. K. Chung and K. P. Fung, “Inhibition of Cell Proliferation in Human Breast Tumor Cells by Antisense Oligonucleotides against Facilitative Glucose Transporter 5,” Journal of Cellular Biochemistry, Vol. 93, No. 6, 2004, pp. 1134-1142. doi:10.1002/jcb.20270
[178] [178] P. J. Goodwin, J. A. Ligibel and V. Stambolic, “Metformin in Breast Cancer: Time for Action,” Journal of Clinical Oncology, Vol. 27, No. 20, 2009, pp. 3271-3273. doi:10.1200/JCO.2009.22.1630
[179] [179] M. Zakikhani, R. Dowling, I. G. Fantus, N. Sonenberg and M. Pollak, “Metformin is an Amp Kinase-Dependent Growth Inhibitor for Breast Cancer Cells,” Cancer Re-search, Vol. 66, No. 21, 2006, pp. 10269-10273. doi:10.1158/0008-5472.CAN-06-1500
[180] [180] J. B. Kim, et al., “The Alkaloid Berberine Inhibits the Growth of Anoikis-Resistant Mcf-7 and Mda-Mb-231 Breast Cancer Cell Lines by Inducing Cell Cycle Arrest,” Phytomedicine, 2009, pp.
[181] [181] J. Yin, H. Xing and J. Ye, “Efficacy of Berberine in Pa-tients with Type 2 Diabetes Mellitus,” Metabolism, Vol. 57, No. 5, 2008, pp. 712-717. doi:10.1016/j.metabol.2008.01.013
[182] [182] L. M. Harhaji Trajkovic, et al., “Anticancer Properties of Ganoderma Lucidum Methanol Extracts in Vitro and in Vivo,” Nutrition and Cancer, Vol. 61, No. 5, 2009, pp. 696-707. doi:10.1080/01635580902898743
[183] [183] Q. Luo, et al., “Lycium Barbarum Polysaccharides Induce Apoptosis in Human Prostate Cancer Cells and Inhibits Prostate Cancer Growth in a Xenograft Mouse Model of Human Prostate Cancer,” Journal of Medicinal Food, Vol. 12, No. 4, 2009, pp. 695-703. doi:10.1089/jmf.2008.1232
[184] [184] P. Wu, J. J. Dugoua, O. Eyawo and E. J. Mills, “Tradi-tional Chinese Medicines in the Treatment of Hepatocel-lular Cancers: A Systematic Review and Meta-Analysis,” Journal of Experimental & Clinical Cancer Research, Vol. 28, 2009, pp. 112. doi:10.1186/1756-9966-28-112
[185] [185] W. Ni, et al., “Antitumor Activities and Immunomodula- tory Effects of Ginseng Neutral Polysaccharides in Com-bination with 5-Fluorouracil,” Journal of Medicinal Food, Vol. 13, No. 2, 2010, pp. 270-277. doi:10.1089/jmf.2009.1119
[186] [186] F. Zou, X. Q. Mao, N. Wang, J. Liu and J. P. Ou-Yang, “Astragalus Polysaccharides Alleviates Glucose Toxicity and Restores Glucose Homeostasis in Diabetic States Via Activation of Ampk,” Acta Pharmacologica Sinica, Vol. 30, No. 12, 2009, pp. 1607-1615. doi:10.1038/aps.2009.168
[187] [187] S. W. Seto, et al., “Novel Hypoglycemic Effects of Gan-oderma Lucidum Water-Extract in Obese/Diabetic (+Db/+Db) Mice,” Phytomedicine, Vol. 16, No. 5, 2009, pp. 426-436. doi:10.1016/j.phymed.2008.10.004
[188] [188] Q. Luo, Y. Cai, J. Yan, M. Sun and H. Corke, “Hypogly-cemic and Hypolipidemic Effects and Antioxidant Activ-ity of Fruit Extracts from Lycium Barbarum,” Life Sci-ences, Vol. 76, No. 2, 2004, pp. 137-149. doi:10.1016/j.lfs.2004.04.056
[189] [189] T. B. Ng and H. W. Yeung, “Hypoglycemic Constituents of Panax Ginseng,” General Pharmacology, Vol. 16, No. 6, 1985, pp. 549-552. doi:10.1016/0306-3623(85)90140-5
[190] [190] J. C. Chen, et al., “Gypenosides Induced G0/G1 Arrest Via Chk2 and Apoptosis through Endoplasmic Reticulum Stress and Mitochondria-Dependent Pathways in Human Tongue Cancer Scc-4 Cells,” Oral Oncology, Vol. 45, No. 3, 2009, pp. 273-283. doi:10.1016/j.oraloncology.2008.05.012
[191] [191] S. Megalli, N. M. Davies and B. D. Roufogalis, “Anti- Hyperlipidemic and Hypoglycemic Effects of Gy-nostemma Pentaphyllum in the Zucker Fatty Rat,” Jour-nal of Pharmacy & Pharmaceutical Sciences, Vol. 9, No. 3, 2006, pp. 281-291.
[192] [192] D. Lamoral-Theys, et al., “Natural Polyphenols That Display Anticancer Properties through Inhibition of Kinase Activity,” Current Medicinal Chemistry, Vol. 17, No. 9, 812-825. doi:10.2174/092986710790712183
[193] [193] J. Ravindran, S. Prasad and B. B. Aggarwal, “Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tu-mor Cells Selectively?” The AAPS Journal, Vol. 11, No. 3, 2009, pp. 495-510. doi:10.1208/s12248-009-9128-x
[194] [194] T. Osawa and Y. Kato, “Protective Role of Antioxidative Food Factors in Oxidative Stress Caused by Hyperglycemia,” Annals of the New York Academy of Sciences, Vol. 1043, 2005, pp. 440-451. doi:10.1196/annals.1333.050

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