Energy metabolism in tumor cells

FEBS Journal

Volumn 274, Issue 6, 2007, Pages 1393-1418

  Moreno Sánchez, Rafael ^a   Rodríguez Enríquez, Sara ^a   Marín Hernández, Alvaro ^a   Saavedra, Emma ^a  

^a INSTITUTO NACIONAL DE CARDIOLOGÍA IGNACIO CHÁVEZ   (Mexico)

Author keywords

Casiopeinas; Chemotherapy; Glycolysis; Metabolic control analysis; Mitochondrial metabolism; PET; Rhodamines

Indexed keywords

1 ETHYL 2 [[3 ETHYL 5 (3 METHYLBENZOTHIAZOLIN 2 YLIDENE) 4 OXOTHIAZOLIDIN 2 YLIDENE]METHYL]PYRIDINIUM CHLORIDE; 6 PHOSPHOFRUCTOKINASE; ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; BROMOPYRUVIC ACID; CARBOXYATRACTYLOSIDE; CASIOPEINA; CITRININ; CLOFAZIMINE; DEOXYGLUCOSE; F 16; GENISTEIN; GLUCOSE TRANSPORTER; GLYCOLYTIC ENZYME; GOSSYPOL; HEXOKINASE; IMATINIB; LONIDAMIDE; MITOCHONDRIAL DNA; NONSTEROID ANTIINFLAMMATORY AGENT; OLIGOMYCIN; OXYGEN; PROTEIN TYROSINE KINASE INHIBITOR; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; PYRUVIC ACID DERIVATIVE; RHODAMINE 123; RHODAMINE 6G; ROTENONE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AEROBIC METABOLISM; BREAST CANCER; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CARCINOSARCOMA; CELL LINE; CELL PROLIFERATION; CHEMICAL ANALYSIS; CITRIC ACID CYCLE; CONCENTRATION (PARAMETERS); ENERGY METABOLISM; ENZYME INHIBITION; ENZYME SUBSTRATE; GENETIC ANALYSIS; GLIOBLASTOMA; GLYCOLYSIS; HUMAN; HYPOXIA; LEUKEMIA; LIVER CELL CARCINOMA; LOW DRUG DOSE; MELANOMA; MITOCHONDRION; NONHUMAN; OSTEOSARCOMA; OXIDATIVE PHOSPHORYLATION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RESPIRATORY CHAIN; REVIEW; TRANSCRIPTION REGULATION; TUMOR; TUMOR CELL;

ENERGY METABOLISM; GLYCOLYSIS; HUMANS; MITOCHONDRIA; NEOPLASMS; OXIDATIVE PHOSPHORYLATION; PROTEIN ISOFORMS;

EID: 33847367741     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2007.05686.x     Document Type: Review

References (193)

1. Pedersen PL (1978) Tumor mitochondria and the bioenergetics of cancer cells. Prog Exp Tumor Res 22, 190-274.
2. Weber G (2001) Ordered biochemical program of gene expression in cancer cells. Biochemistry (Moscow) 66, 1164-1173.
3. Zu XL & Guppy M (2004) Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun 313, 459-465.
4. Lowry OH, Berger SJ, Carter JG, Chi MM, Manchester JK, Knor J & Pusateri ME (1983) Diversity of metabolic patterns in human brain tumors: enzymes of energy metabolism and related metabolites and cofactors. J Neurochem 41, 994-1010.
5. Dastidar SG & Sharma SK (1989) Activities of glycolytic enzymes in rapidly proliferating and differentiated C6 glioma cells. Exp Cell Biol 57, 159-164.
6. Mazurek S, Michel A & Eigenbrodt E (1997) Effect of extracellular AMP on cell proliferation and metabolism of breast cancer cell lines with high and low glycolytic rates. J Biol Chem 272, 4941-4952.
7. Rodríguez-Enríquez S, Torres-Márquez ME & Moreno-Sánchez R (2000) Substrate oxidation and ATP supply in AS-30D hepatoma cells. Arch Biochem Biophys 375, 21-30.
8. Ziegler A, Von Kienlin M, Decorps M & Remy C (2001) High glycolytic activity in rat glioma demonstrated in vivo by correlation peak 1H magnetic resonance imaging. Cancer Res 61, 5595-5600.
9. Griguer CE, Oliva CR & Gillespie GY (2005) Glucose metabolism heterogeneity in human and mouse malignant glioma cell lines. J Neurooncol 74, 123-133.
10. Gatenby RA & Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4, 891-899.
11. Marin-Hernandez A, Rodriguez-Enriquez S, Vital-Gonzalez PA, Flores-Rodriguez FL, Macias-Silva M, Sosa-Garrocho M & Moreno-Sanchez R (2006) Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an overexpressed but strongly product-inhibited hexokinase. FEBS J 273, 1975-1988.
12. Meienhofer MC, De Medicis E, Cognet M & Kahn A (1978) Regulation of genes for glycolytic enzimes in cultured rat hepatoma cell lines. Eur J Biochem 169, 237-243.
13. Dang CV, Lewis BC, Dolde C, Dang G & Shim H (1997) Oncogenes in tumor metabolism, tumorigenesis, and apoptosis. J Bioenerg Biomembr 29, 345-354.
14. Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA & Dang CV (2000) Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem 275, 21797-21800.
15. Atsumi T, Chesney J, Metz C, Leng L, Donnelly S, Makita Z, Mitchell T & Bucala R (2002) High expression of inducible 6-phosphofructo-2-kinase/ fructose 2,6-bisphosphatase (iPFK-2: PFKFB3) in human cancers. Cancer Res 62, 5881-5887.
16. Nakashima RA, Paggi MG, Scott LJ & Pedersen PL (1988) Purification and characterization of bindable form of mitochondrial bound hexokinase from the highly glycolytic AS-30D rat hepatoma cell line. Cancer Res 48, 913-919.
17. Stubbs M, Bashford CL & Griffiths JR (2003) Understanding the tumor-metabolic phenotype in the genomic era. Curr Mol Med 3, 49-59.
18. Balinsky D, Platz CE & Lewis JW (1984) Enzyme activities in normal, dysplastic, and cancerous human breast tissues. J Natl Cancer Inst 72, 217-224.
19. Semenza GL (2000) HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88, 1474-1480.
20. Guppy M, Leedman P, Zu XL & Russell V (2002) Contribution by different fuels and metabolic pathways to the total ATP turnover of proliferating MCF-7 breast cancer cells. Biochem J 364, 309-315.
21. Dalgard CL, Lu H, Mohyeldin A & Verma A (2004) Endogenous 2-oxoacids regulate expression of oxygen sensors. Biochem J 380, 419-424.
22. Thomas DD, Espey MG, Ridnour LA, Hofseth LJ, Mancardi D, Harris CC & Wink DA (2004) Hypoxic inducible factor 1 alpha, extracellular signal-regulated kinase, and p53 are regulated by distinct threshold concentrations of nitric oxide. Proc Natl Acad Sci USA 101, 8894-8899.
23. Robey IF, Lien AD, Welsh SJ, Baggett BK & Gillies RJ (2005) Hypoxia-inducible factor-1α and the glycolytic phenotype in tumors. Neoplasia 7, 324-330.
24. Dang CV & Semenza GL (1999) Oncogenic alterations of metabolism. Trends Biochem Sci 24, 68-72.
25. Minchenko O, Opentanova I & 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.
26. Simon MC (2006) Coming up for air: HIF-1 and mitochondrial oxygen consumption. Cell Metab 3, 150-151.
27. Rapoport TA, Heinrich R & Rapoport SM (1976) The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes. Biochem J 154, 449-469.
28. Torres NV, Mateo F, Meléndez-Hevia E & Kacser H (1986) Kinetics of metabolic pathways. Biochem J 234, 169-174.
29. Torres NV, Souto R & Meléndez-Hevia E (1989) Study of flux and transition time control coefficient profiles in a metabolic system in vitro and the effect of an external stimulator. Biochem J 260, 763-769.
30. Kashiwaya YK, Sato K, Tsuchiya N, Thomas S, Fell DA, Veech RL & Passonneau JV (1994) Control of glucose utilization in working perfused rat heart. J Biol Chem 269, 25502-25514.
31. Bustamante E & Pedersen PL (1977) High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. Proc Natl Acad Sci USA 74, 3735-3739.
32. Vora S, Halper JP & Knowles DM (1985) Alterations in the activity and isozymic profile of human phospho-fructokinase during malignant transformation in vivo and in vitro: transformation-and progression-linked discriminants of malignancy. Cancer Res 45, 2993-3001.
33. Sánchez-Martínez C & Aragón JJ (1997) Analysis of phosphofructokinase subunits and isozymes in ascites tumor cells and its original tissue, murine mammary gland. FEBS Lett 409, 86-90.
34. Medina RA & Owen GI (2002) Glucose transporters: expression, regulation and cancer. Biol Res 35, 9-26.
35. Wood IS & Trayhurn P (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89, 3-9.
36. Macheda ML, Rogers S & Best JD (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202, 654-662.
37. Fung KP, Choy YM, Chan TW, Lam WP & Lee CY (1986) Glucose regulates its own transport in Ehrlich ascites tumour cells. Biochem Biophys Res Commun 134, 1231-1237.
38. Medina RA, Meneses AM, Vera JC, Guzmán C, Nualart F, Rodriguez F, de los Angeles Garcia M, Kato S, Espinoza N, Monso C et al. (2004) Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells. J Endocrinol 182, 467-478.
39. Christopher CW, Kohlbacher MS & Amos H (1976) Transport of sugars in chick-embryo fibroblasts. Evidence for a low-affinity system and a high-affinity system for glucose transport. Biochem J 158, 439-450.
40. Lane RH, Crawford SE, Flozak AS & Simmons RA (1999) Localization and quantification of glucose transporters in liver of growth-retarded fetal and neonatal rats. Am J Physiol 276, E135-E142.
41. Cornish-Bowden A & Cardenas ML (1991) Hexokinase and glucokinase in liver metabolism. Trends Biochem Sci 16, 281-282.
42. Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206, 2049-2057.
43. Pedersen PL, Mathupala S, Rempel A, Geschwind JF & Ko YH (2002) Mitochondrial bound type II hexokinase. Biochim Biophys Acta 1555, 14-20.
44. Parry DM & Pedersen PL (1983) Intracellular localization and properties of particulate hexokinase in the Novikoff ascites tumor. J Biol Chem 258, 10904-10912.
45. Bennett MJ, Timperley WR, Taylor CB & Hill AS (1978) Isoenzymes of hexokinase in the developing, normal and neoplastic human brain. Eur J Cancer 14, 189-193.
46. Beutner G, Ruck A, Riede B, Welte W & Brdiczka D (1996) Complex between kinases, mitochondrial porin and adenylate translocator in rat brain resemble the permeability transition pore. FEBS Lett 396, 189-195.
47. Shimizu S, Ide T, Yanagida T & Tsujimoto Y (2000) Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c. J Biol Chem 275, 12321-12325.
48. Pastorino JG, Shulga N & Hoek JB (2002) Mitochondrial binding of hexokinase II inhibits Bax induced cytochrome c release and apoptosis. J Biol Chem 277, 7610-7618.
49. Seixas da-Silva W, Gómez-Puyou A, Tuena M, Moreno-Sánchez R, de Felice FG, de Meis L, Oliveira MF & Galina A (2004) Mitochondrial bound hexokinase activity as a preventive antioxidant defense. J Biol Chem 279, 39846-39855.
50. Dunaway GA, Kasten TP, Sebo T & Trapp R (1988) Analysis of the phosphofructokinase subunits and isoenzymes in human tissues. Biochem J 251, 677-683.
51. Oskam R, Rijksen G, Staal GEJ & Vora S (1985) Isozymic composition and regulatory properties of phosphofructokinase from well-differentiated and anaplastic medullary thyroid carcinomas of the rat. Cancer Res 45, 135-142.
52. Staal GEJ, Kalff A, Heesbeen EC, van Veelen CWM & Rijksen G (1987) Subunit composition, regulatory properties, and phosphorylation of phosphofructokinase from human gliomas. Cancer Res 47, 5047-5051.
53. Sánchez-Martínez C, Estévez AM & Aragón JJ (2000) Phosphofructokinase C isozyme from ascites tumor cells: cloning, expression, and properties. Biochem Biophys Res Commun 271, 635-640.
54. Meldolesi MF, Macchia V & Laccetti P (1976) Differences in phosphofructokinase regulation in normal and tumor rat thyroid cells. J Biol Chem 251, 6244-6251.
55. Rider MH, Bertrand L, Vertommen D, Michels PA, Rousseau GG & Hue L (2004) 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis. Biochem J 381, 561-579.
56. Hirata T, Kato M, Okamura N, Fukasawa M & Sakakibara R (1998) Expression of human placental-type 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in various cells and cells lines. Biochem Biophys Res Commun 242, 680-684.
57. Calvo MN, Bartrons R, Castaño E, Perales JC, Navarro-Sabate A & Manzano A (2006) PFKFB3 gene silencing decreases glycolysis, induces cell-cycle delay and inhibits anchorage-independent growth in HeLa cells. FEBS Lett 580, 3308-3314.
58. Warburg O (1956) On the origin of cancer cells. Science 123, 309-314.
59. Baggetto LG & Lehninger AL (1987) Formation and utilization of acetoin, an unusual product of pyruvate metabolism by Ehrlich and AS30-D tumor mitochondria. J Biol Chem 262, 9535-9541.
60. Baggetto LG (1992) Deviant energetic metabolism of glycolytic cancer cells. Biochimie 74, 959-974.
61. Paradies G, Capuano F, Palombini G, Galeotti T & Papa S (1983) Transport of pyruvate in mitochondria from different tumor cells. Cancer Res 43, 5068-5071.
62. Lindahl R (1979) Subcellular distribution and properties of aldehyde dehydrogenase from 2-acetyl-aminofluorene-induced rat hepatomas. Biochem J 183, 55-64.
63. Lazo PA & Sols A (1980) Pyruvate dehydrogenase complex of ascites tumour. Activation by AMP and other properties of potential significance in metabolic regulation. Biochem J 190, 705-710.
64. Rodríguez-Enríquez S, Juárez O, Rodríguez- Zavala JS & Moreno-Sánchez R (2001) Multisite control of the Crabtree effect in ascites hepatoma cells. Eur J Biochem 268, 2512-2519.
65. Eboli ML, Paradies G, Galeotti T & Papa S (1977) Pyruvate transport in tumour-cell mitochondria. Biochim Biophys Acta 460, 183-187.
66. Parlo RA & Coleman PS (1984) Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria. The truncated Krebs cycle and other metabolic ramifications of mitochondrial membrane cholesterol. J Biol Chem 259, 9997-10003.
67. Dietzen DJ & Davis EJ (1993) Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS-30D hepatoma mitochondria. Arch Biochem Biophys 305, 91-102.
68. Briscoe DA, Fiskum G, Holleran AL & Kelleher JK (1994) Acetoacetate metabolism in AS-30D hepatoma cells. Mol Cell Biochem 136, 131-137.
69. Boxer GE & Devlin TM (1961) Pathways of intracellular hydrogen transport. Science 134, 1495-1501.
70. Grivell AR, Korpelainen EI, Williams CJ & Berry MN (1995) Substrate-dependent utilization of the glycerol 3-phosphate or malate/aspartate redox shuttles by Ehrlich ascites cells. Biochem J 310, 665-671.
71. Rodriguez-Enriquez S, Kim I, Currin RT & Lemasters JJ (2006) Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2, 39-46.
72. LaNoue KF, Hemington JG, Ohnishi T, Morris HP & Williamson JR (1974) Defects in anion and electron transport in Morris hepatoma mitochondria. In Hormones and Cancer (McKerns KW, ed.), pp. 131-167. Academic Press, New York.
73. White MT & Nandi S (1976) Biochemical studies on mitochondria isolated from normal and neoplasic tissues of the mouse mammary gland. J Natl Cancer Inst 56, 65-73.
74. Lichtor T & Dohrmann GJ (1987) Oxidative metabolism and glycolysis in benign brain tumors. J Neurosurg 67, 336-340.
75. Barbour RL & Chan SH (1983) Adenine nucleotide transport in hepatoma mitochondria and its correlation with hepatoma growth rates and tumor size. Cancer Res 43, 1511-1517.
76. Torroni A, Stepien G, Hodge JA & Wallace DC (1990) Neoplastic transformation is associated with coordinate induction of nuclear and cytoplasmic oxidative phosphorylation genes. J Biol Chem 265, 20589-20593.
77. 1 ATP synthase activity of human hepatocellular carcinoma. Biochem Mol Biol Int 38, 1013-1022.
78. Pedersen PL, Greenawalt JW, Chan TL & Morris HP (1970) A comparison of some ultrastructural and biochemical properties of mitochondria from Morris hepatomas 9618A, 7800, and 3924A. Cancer Res 30, 2620-2626.
79. White MT & Tewari KK (1973) Structural and functional changes in Novikoff hepatoma mitochondria. Cancer Res 33, 1645-1653.
80. Sauer LA (1977) On the mechanism of the Crabtree effect in mouse ascites tumor cells. J Cell Physiol 93, 313-316.
81. Sussman I, Erecinska M & Wilson DF (1980) Regulation of cellular energy metabolism: the Crabtree effect. Biochim Biophys Acta 591, 209-223.
82. Sener A, Blachier F & Malaisse WJ (1988) Crabtree effect in tumoral pancreatic islet cells. J Biol Cell 263, 1904-1909.
83. Gabai VL (1992) Glucose decreases respiratory control ratio in EL-4 tumor cells. FEBS Lett 313, 126-128.
84. Melo RF, Stevan FR, Campello AP, Carnieri EG & de Oliveira MB (1998) Occurrence of the Crabtree effect in HeLa cells. Cell Biochem Funct 16, 99-105.
85. Gauthier T, Denis-Pouxviel C & Murat JC (1990) Respiration of mitochondria isolated from differentiated and undifferentiated HT29 colon cancer cells in the presence of various substrates and ADP generating systems. Int J Biochem 22, 411-417.
86. Seshagiri PB & Bavister BD (1991) Glucose and phosphate inhibit respiration and oxidative metabolism in cultured hamster eight-cell embryos: evidence for the 'crabtree effect'. Mol Reprod Dev 30, 105-111.
87. Yang X, Borg LA & Eriksson UJ (1997) Altered metabolism and superoxide generation in neural tissue of rat embryos exposed to high glucose. Am J Physiol 272, E173-E180.
88. 2+ in rat heart mitochondria. J Biol Chem 273, 7850-7855.
89. Covian R & Moreno-Sanchez R (2001) Role of protonatable groups of bovine heart bc(1) complex in ubiquinol binding and oxidation. Eur J Biochem 268, 5783-5790.
90. Luciakova K & Kuzela S (1984) Increased content of natural ATPase inhibitor in tumor mitochondria. FEBS Lett 177, 85-88.
91. Bravo C, Minauro-Sanmiguel F, Morales-Rios E, Rodriguez-Zavala JS & Garcia JJ (2004) Overexpression of the inhibitor protein IF(1) in AS-30D hepatoma produces a higher association with mitochondrial F(1)F(0) ATP synthase compared to normal rat liver: functional and cross-linking studies. J Bioenerg Biomembr 36, 257-264.
92. Solaini G & Harris DA (2005) Biochemical dysfunction in heart mitochondria exposed to ischaemia and respiration. Biochem J 390, 377-394.
93. Penta JS, Johnson FM, Wachsman JT & Copeland WC (2001) Mitochondrial DNA in human malignancy. Mutat Res 488, 119-133.
94. Carew JS & Huang P (2002) Mitochondrial defects in cancer. Mol Cancer 1, 1-9.
95. Meierhofer D, Mayr JA, Fink K, Schmeller N, Kofler B & Sperl W (2006) Mitochondrial DNA mutations in renal cell carcinomas revealed no general impact on energy metabolism. Br J Cancer 94, 268-274.
96. Bonora E, Porcelli AM, Gasparre G, Biondi A, Ghelli A, Carelli V, Baracca A, Tallini G, Martinuzzi A, Lenaz G et al. (2006) Defective oxidative phosphorylation in thyroid oncocytic carcinoma is associated with pathogenic mitochondrial DNA mutations affecting complexes I and III. Cancer Res 66, 6087-6096.
97. Xu R, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ & 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.
98. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F & Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312, 1650-1653.
99. Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ & Capaldi RA (2004) Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 64, 985-993.
100. Seyfried TN & Mukherjee P (2005) Targeting energy metabolism in brain cancer: review and hypothesis. Nutr Metabol 2, 30-38.
101. Eskey CJ, Koretsky AP, Domach MM & Jain RK (1993) Role of oxygen versus glucose in energy metabolism in a mammary carcinoma perfused ex vivo: direct measurement by 31P NMR. Proc Natl Acad Sci USA 90, 2646-2650.
102. Thews O, Kelleher DK, Lecher B & Vaupel P (1998) Blood flow, oxygenation, metabolic and energetic status in different clonal subpopulations of a rat rhabdomyosarcoma. Int J Oncol 13, 205-211.
103. Rofstad EK & Halsor EF (2000) Vascular endothelial growth factor, interleukin 8, platelet-derived endothelial cell growth factor, and basic fibroblast growth factor promote angiogenesis and metastasis in human melanoma xenografts. Cancer Res 60, 4932-4938.
104. Sutherland RM (1988) Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 240, 177-184.
105. Schroeder T, Yuan H, Viglianti BL, Peltz C, Asopa S, Vujaskovic Z & Dewhirst MW (2005) Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat. Cancer Res 65, 5163-5171.
106. Vaupel P, Kallinowski F & Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49, 6449-6465.
107. Gorlach A & Acker H (1994) pO2- and pH-gradients in multicellular spheroids and their relationship to cellular metabolism and radiation sensitivity of malignant human tumor cells. Biochim Biophys Acta 1227, 105-112.
108. Sutherland RM (1998) Tumor hypoxia and gene expression. Acta Oncol 37, 567-574.
109. Matsumoto A, Matsumoto S, Sowers AL, Koscielniak JW, Trigg NJ, Kuppusamy P, Mitchell JB, Subramanian S, Krishna MC & Matsumoto K (2005) Absolute oxygen tension (pO(2)) in murine fatty and muscle tissue as determined by EPR. Magn Reson Med 54, 1530-1535.
110. Inoue M, Mukai M, Hamanaka Y, Tatsuta M, Hiraoka M & Kizaka-Kondoh S (2004) Targeting hypoxic cancer cells with a protein prodrug is effective in experimental malignant ascites. Int J Oncol 25, 713-720.
111. Mason MG, Nicholls P, Wilson MT & Cooper CE (2006) Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase. Proc Natl Acad Sci USA 103, 708-713.
112. Gnaiger E, Lassnig B, Kuznetsov A, Rieger G & Margreiter R (1998) Mitochondrial oxygen affinity, respiratory flux control and excess capacity of cytochrome c oxidase. J Exp Biol 201, 1129-1139.
113. Pecina P, Gnaiger E, Zeman J, Pronicka E & Houštěk T (2004) Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations. Am J Physiol Cell Physiol 287, C1384-C1388.
114. Nielsen FU, Daugaard P, Bentzen L, Stodkilde-Jorgensen H, Overgaard J, Horsman MR & Maxwell RJ (2001) Effect of changing tumor oxygenation on glycolytic metabolism in a murine C3H mammary carcinoma assessed by in vivo nuclear magnetic resonance spectroscopy. Cancer Res 61, 5318-5325.
115. Board M, Humm S & Newsholme EA (1990) Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. Biochem J 265, 503-509.
116. Reitzer LJ, Wice BM & Kennell D (1979) Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 254, 2669-2676.
117. Rodriguez-Enriquez S, Vital-Gonzalez PA, Flores-Rodriguez FL, Marin-Hernandez A, Ruiz-Azuara L & Moreno-Sanchez R (2006) Control of cellular proliferation by modulation of oxidative phosphorylation in human and rodent fast-growing tumor cells. Toxicol Appl Pharmacol 215, 208-217.
118. Medina MA (2001) Glutamine and cancer. J Nutr 131, 2539 S-2542 S.
119. Muller M, Siems W, Buttgereit F, Dumdey R & Rapoport SM (1986) Quantification of ATP-producing and consuming processes of Ehrlich ascites tumour cells. Eur J Biochem 161, 701-705.
120. Schmidt H, Siems W, Muller M, Dumdey R & Rapoport S (1991) ATP-producing and consuming processes of Ehrlich mouse ascites tumor cells in proliferating and resting phases. Exp Cell Res 194, 122-127.
121. Weinhouse S (1956) On respiratory impairment in cancer cells. Science 124, 267-269.
122. Miralpeix M, Azcon-Breto J, Bartrons R & Argilés JM (1990) The impairment of respiration by glycolysis in the Lewis lung carcinoma. Cancer Lett 50, 173-178.
123. Kallinowski F, Schlenger KH, Kloes M, Stohrer M & Vaupel P (1989) Tumor blood flow: the principal modulator of oxidative and glycolytic metabolism, and of the metabolic micromilieu of human tumor xenografts in vivo. Int J Cancer 44, 266-272.
124. Lanks KW & Li PW (1988) End products of glucose and glutamine metabolism by cultured cell lines. J Cell Physiol 135, 151-155.
125. Fantin VR, St-Pierre J & Leder P (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9, 425-434.
126. Moreadith RW & Lehninger AL (1984) Purification, kinetic behavior, and regulation of NAD(P)+ malic enzyme of tumor mitochondria. J Biol Chem 259, 6222-6227.
127. Mandella RD & Sauer LA (1975) The mitochondrial malic enzymes. I. Submitochondrial localization and purification and properties of the NAD(P)+-dependent enzyme from adrenal cortex. J Biol Chem 250, 5877-5884.
128. Molina M, Segura JA, Aledo JC, Medina MA, Nunez de Castro I & Marquez J (1995) Glutamine transport by vesicles isolated from tumour-cell mitochondrial inner membrane. Biochem J 308, 629-633.
129. Matsuno T & Goto I (1992) Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma. Cancer Res 52, 1192-1194.
130. Fell D (1997) Understanding the Control of Metabolism. Portland Press, London.
131. Groen AK, Wanders RJ, Westerhoff HV, Van der Meer R & Tager JM (1982) Quantification of the contribution of various steps to the control of mitochondrial respiration. J Biol Chem 257, 2754-2757.
132. Moreno-Sanchez R & Torres-Marquez ME (1991) Control of oxidative phosphorylation in mitochondria, cells and tissues. Int J Biochem 23, 1163-1174.
133. Krieg RC, Knuechel R, Schiffmann E, Liotta LA, Petricoin EF III & Herrmann PC (2004) Mitochondrial proteome: cancer-altered metabolism associated with cytochrome c oxidase subunit level variation. Proteomics 4, 2789-2795.
134. Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK & Mueller-Klieser W (2000) High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 60, 916-921.
135. Soderberg K, Nissinen E, Bakay B & Scheffler IE (1980) The energy charge in wild-type and respiration-deficient Chinese hamster cell mutants. J Cell Physiol 103, 169-172.
136. Gear AR (1974) Rhodamine 6G. A potent inhibitor of mitochondrial oxidative phosphorylation. J Biol Chem 249, 3628-3637.
137. Fearon KC, Plumb JA, Burns HJ & Calman KC (1987) Reduction of the growth rate of the Walker 256 tumor in rats by rhodamine 6G together with hypoglycemia. Cancer Res 47, 3684-3687.
138. Lambeir AM, Loiseau AM, Kuntz DA, Vellieux FM, Michels PA & Opperdoes FR (1991) The cytosolic and glycosomal glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma brucei. Kinetic properties and comparison with homologous enzymes. Eur J Biochem 198, 429-435.
139. Coyle T, Levante S, Shetler M & Wintield J (1994) In vitro and in vivo cytotoxicity of gossypol against central nervous system tumor cell lines. J Neurooncol 19, 25-35.
140. Jaroszewski JW, Kaplan O & Cohen JS (1990) Action of gossypol and rhodamine 123 on wild-type and multidrug-resistant MCF-7 human breast cancer cells: 31P nuclear magnetic resonance and toxicity studies. Cancer Res 50, 6936-6943.
141. Liu H, Hu YP, Savaraj N, Priebe W & Lampidis TJ (2001) Hypersensitization of tumor cells to glycolytic inhibitors. Biochemistry 40, 5542-5547.
142. Lampidis TJ, Bernal SD, Summerhayes IC & Chen LB (1983) Selective toxicity of rhodamine 123 in carcinoma cells in vivo. Cancer Res 43, 716-720.
143. Bernal SD, Lampidis TJ, McIsaac RM & Chen LB (1983) Antisarcoma activity in vivo of rhodamine 123, a mitochondrial-specific dye. Science 222, 169-172.
144. Sri-Pathmanathan RM, Plumb JA & Fearon KC (1994) Clofazimine alters the energy metabolism and inhibits the growth rate of a human lung-cancer cell line in vitro and in vivo. Int J Cancer 56, 900-905.
145. Fantin VR, Berardi MJ, Scorrano L, Korsmeyer SJ & Leder P (2002) A novel mitochondriotoxic small molecule that selectively inhibits tumor cell growth. Cancer Cell 2, 29-42.
146. Koya K, Li Y, Wang H, Ukai T, Tatsuta N, Kawakami M & Shishido & Chen LB (1996) MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation. Cancer Res 56, 538-543.
147. Ko YH, Pedersen PL & Geschwind JF (2001) Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer Lett 173, 83-91.
148. Geschwind JF, Ko YH, Torbenson MS, Magee C & Pedersen PL (2002) Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production. Cancer Res 62, 3909-3913.
149. Sweet S & Singh G (1995) Accumulation of human promyelocytic leukemic (HL-60) cells at two energetic cell cycle checkpoints. Cancer Res 55, 5164-5167.
150. Armstrong JS, Hornung B, Lecane P, Jones DP & Knox SJ (2001) Rotenone-induced G2/M cell cycle arrest and apoptosis in a human B lymphoma cell line PW. Biochem Biophys Res Commun 289, 973-978.
151. Barrientos A & Moraes CT (1999) Titrating the effects of mitochondrial complex I impairment in the cell physiology. J Biol Chem 274, 16188-16197.
152. Fanciulli M, Valentini A, Bruno T, Citro G & Zupi & Floridi A (1996) Effect of the antitumor drug lonidamine on glucose metabolism of adriamycin-sensitive and -resistant human breast cancer cells. Oncol Res 8, 111-1120.
153. De Martino C, Malorni W, Accinni L, Rosati F, Nista A, Formisano G, Silvestrini B & Arancia G (1987) Cell membrane changes induced by lonidamine in human erythrocytes and T lymphocytes, and Ehrlich ascites tumor cells. Exp Mol Pathol 46, 15-30.
154. Gottschalk S, Anderson N, Hainz C, Eckhardt SG & Serkova NJ (2004) Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res 10, 6661-6668.
155. Fiorentini D, Hakim G, Bonsi L, Bagnara GP, Maraldi T & Landi L (2001) Acute regulation of glucose transport in a human megakaryocytic cell line: difference between growth factors and H(2)O(2). Free Rad Biol Med 31, 923-931.
156. Fosslien E (2000) Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia. Crit Rev Clin Lab Sci 37, 431-502.
157. Kune GA, Kune S & Watson LF (1988) Colorectal cancer risk, chronic illness, operations and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48, 4399-4404.
158. Lundholm K, Gelin J, Hyltander A, Lonnroth C, Sandstrom R, Svaninger G, Korner U, Gulich M, Karrefors I, Norli B et al. (1994) Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res 54, 5602-5606.
159. Cahlin C, Gelin J, Andersson M, Lonnroth C & Lundholm K (2005) The effects of non-selective, preferential-selective and selective COX-inhibitors on the growth of experimental and human tumors in mice related to protanoid receptors. Int J Oncol 27, 913-923.
160. Moreno-Sánchez R, Bravo C, Vásquez C, Ayala G, Silveira L & Martínez-Lavín M (1999) Inhibition and uncoupling of oxidative phosphorylation by nonsteroidal anti-inflammatory drugs: study in mitochondria, submitochondrial particles, cells, and whole heart. Biochem Pharmacol 57, 743-752.
161. Fisher PG & Buffler PA (2005) Malignant gliomas in 2005: where to GO from here? JAMA 293, 615-617.
162. Dairkee SH & Hackett AJ (1991) Differential retention of rhodamine 123 by breast carcinoma and normal human mammary tissue. Breast Cancer Res Treat 18, 57-61.
163. Davis S, Weiss MJ, Wong JR, Lampidis TJ & Chen LB (1985) Mitochondrial and plasma membrane potentials cause unusual accumulation and retention of rhodamine 123 by human breast adenocarcinoma-derived MCF-7 cells. J Biol Chem 260, 13844-13850.
164. Dietzen DJ & Davis EJ (1994) Excess membrane cholesterol is not responsible for metabolic and bioenergetic changes in AS-30D hepatoma mitochondria. Arch Biochem Biophys 309, 341-347.
165. Hu Y, Moraes CT, Savaraj N, Priebe W & Lampidis TJ (2000) Rho(0) tumor cells: a model for studying whether mitochondria are targets for rhodamine 123, doxorubicin and other drugs. Biochem Pharmacol 60, 1897-1905.
166. 2+ in pancreas and adrenal cortex mitochondria. Arch Biochem Biophys 319, 432-444.
167. Brown GC, Lakin-Thomas PL & Brand MD (1990) Control of respiration and oxidative phosphorylation in isolated rat liver cells. Eur J Biochem 192, 355-362.
168. Marín-Hernández A, Gracia-Mora I, Ruiz-Ramírez L & Moreno-Sánchez R (2003) Toxic effects of copper-based antineoplastic drugs (Casiopeinas) on mitochondrial functions. Biochem Pharmacol 65, 1979-1989.
169. 18F] fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res 10, 2245-2252.
170. Murphy BJ, Laderoute KR, Chin RJ & Sutherland RJ (1994) Metallothionein IIA is up-regulated by hypoxia in human A431 squamous carcinoma cells. Cancer Res 54, 5808-5810.
171. Dey R & Moraes CT (2000) Lack of oxidative phosphorylation and low mitochondrial membrane potential decrease susceptibility to apoptosis and do not modulate the protective effect of Bcl-x (L) in osteosarcoma cells. J Biol Chem 275, 7087-7094.
172. Navolanic PM & McCubrey JA (2005) Pharmacological breast cancer therapy (review). Int J Oncol 27, 1341-1334.
173. Harper ME, Antoniou A, Villalobos-Manuey E, Russo A, Trauger R, Vendemelio M, George A, Bartholomew R, Carlo D, Shaikh A et al. (2002) Characterization of a novel metabolic strategy used by drug-resistant tumor cells. FASEB J 16, 1550-1557.
174. Marks DC, Su GM, Davey RA & Davey MW (1996) Extended multidrug resistance in haemopoietic cells. Br J Haematol 95, 587-595.
175. Czernin J & Phelps ME (2002) Positron emission tomography scanning: current and future applications. Annu Rev Med 53, 89-112.
176. Seemann MD (2004) PET/CT: Fundamental Principles. Eur J Med Res 28, 241-246.
177. Pauwels EK, Sturm EJ, Bombardieri E, Cleton FJ & Stokkel MP (2000) Positron-emission tomography with [18F]fluorodeoxyglucose. Part I. Biochemical uptake mechanism and its implication for clinical studies. J Cancer Res Clin Oncol 126, 549-559.
178. Schiepers C & Hoh CK (1998) Positron emission tomography as a diagnostic tool in oncology. Eur Radiol 8, 1481-1494.
179. Lassen U, Daugaard G, Eigtved A, Damgaard K & Friberg L (1999) 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT). Eur J Cancer 35, 1076-1082.
180. Chang JM, Lee HJ, Goo JM, Lee HY, Lee JJ, Chung JK & Im JG (2006) False positive and false negative FDG-PET scans in various thoracic diseases. Korean J Radiol 7, 57-69.
181. Haq MS, McCready RM & Harmer CL (2004) Treatment of advanced differentiated thyroid carcinoma with high activity radioiodine therapy. Nucl Med Commun 25, 799-805.
182. 2- polarography in metastatic head and neck cancer. Eur J Nucl Med Mol Imaging 33, 1426-1431.
183. Toyoda M, Sakuragawa N, Arai Y, Yoshikawa H, Sugai K, Arima M, Hara T, Lio M & Satoyoshi E (1989) Positron emission tomography using pyruvate-1-11C in two cases of mitochondrial encephalomyopathy. Ann Nucl Med 3, 103-109.
184. Fujibayashi Y, Taniuchi H, Wada K, Yonekura Y, Konishi J & Yokoyama A (1995) Differential mechanism of retention of Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM) by brain and tumor: a novel radiopharmaceutical for positron emission tomography imaging. Ann Nucl Med 9, 1-5.
185. Rodrigues M, Kalinowska W, Aghajanian AA, Zielinski C & Sinzinger H (2002) Accumulation of TC-99M-MIBI and TC-99M-Tetrofosmin in tumor cells. Uptake and washout studies. AloSbimn J 17, 410.
186. Jana S & Blaufox MD (2006) Nuclear medicine studies of the prostate, testes, and bladder. Semin Nucl Med 36, 51-72.
187. Liu Y (2006) Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer. Prostate Cancer Prostatic Dis 9, 230-234.
188. Gracia-Mora I, Ruiz-Ramirez L, Gomez-Ruiz C, Tinoco-Mendez M, Marquez-Quiñones A, Romero-De Lira L, Marin-Hernandez A, Macias-Rosales L & Bravo-Gómez ME (2001) Knigth's move in the periodic table, from copper to platinum, novel antitumor mixed chelate copper compounds, casiopeinas, evaluated by an in vitro human and murine cancer cell line panel. Metal Based Drugs 8, 19-28.
189. Kong D, Park EJ, Stephen AG, Calvani M, Cardellina JH, Monks A, Fisher RJ, Shoemaker RH & Melillo G (2005) Echinomycin, a small molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res 65, 9047-9055.
190. Ziegler A, Von Kienlin M, Decorps M & Remy C (2001) High glycolytic activity in rat glioma demonstrated in vivo by correlation peak 1H magnetic resonance imaging. Cancer Res 61, 5595-5600.
191. Balaban RS & Bader JP (1984) Studies on the relationship between glycolysis and (Na++ K+)-ATPase in cultured cells. Biochim Biophys Acta 804, 419-426.
192. Fanciulli M, Bruno T, Castiglione S, Del Carlo C, Paggi MG & Floridi A (1993) Glucose metabolism in adriamycin-sensitive and -resistant LoVo human colon carcinoma cells. Oncol Res 5, 357-362.
193. Elwood JC, Lin YC, Cristofalo VJ, Wienhouse S & Morris HP (1963) Glucose utilization in homogenates of the Morris hepatoma 5123 and related tumors. Cancer Res 23, 906-913.