Canonical and new generation anticancer drugs also target energy metabolism

Archives of Toxicology

Volumn 88, Issue 7, 2014, Pages 1327-1350

  Rodríguez Enríquez, Sara ^a,b   Gallardo Pérez, Juan Carlos ^a   Hernández Reséndiz, Ileana ^a   Marín Hernández, Alvaro ^a   Pacheco Velázquez, Silvia C ^a   López Ramírez, Sayra Y ^a   Rumjanek, Franklin D ^c   Moreno Sánchez, Rafael ^a  

^a INSTITUTO NACIONAL DE CARDIOLOGÍA IGNACIO CHÁVEZ   (Mexico)

^b INSTITUTO NACIONAL DE CANCEROLOGÍA   (Mexico)

^c FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Energy metabolism; Humanized monoclonal antibodies; Metabolic therapy; Protein kinase inhibitors; Tumor cells

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; BEVACIZUMAB; GLYCOLYTIC ENZYME; LETROZOLE; MITOCHONDRIAL DNA; MITOCHONDRIAL ENZYME; MITOMYCIN; PROTEASOME INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; TRASTUZUMAB; VALPROIC ACID;

ANTIPROLIFERATIVE ACTIVITY; CANCER CELL; CANCER CHEMOTHERAPY; CELL VIABILITY; DNA MODIFICATION; ENERGY METABOLISM; ENZYME ACTIVITY; EPIGENETICS; GLYCOLYSIS; HUMAN; METASTASIS; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; RESPIRATORY CHAIN; REVIEW; SOLID TUMOR; ANIMAL; DRUG DESIGN; DRUG EFFECTS; METABOLISM; MITOCHONDRION; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PATHOLOGY;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; ENERGY METABOLISM; GLYCOLYSIS; HUMANS; MITOCHONDRIA; MOLECULAR TARGETED THERAPY; NEOPLASMS;

EID: 84903457815     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-014-1246-2     Document Type: Review

References (210)

1. Abdel-aleem S, el-Merzabani MM, Sayed-Ahmed M, Taylor DA, Lowe JE (1997) Acute and chronic effects of adriamycin on fatty acid oxidation in isolated cardiac myocytes. J Mol Cell Cardiol 29:789-797. doi:10.1006/jmcc.1996.0323 (Pubitemid 27192884)
2. Aggarwal SK (1993) A histochemical approach to the mechanism of action of cisplatin and its analogues. J Histochem Cytochem 41:1053-1073. doi:10.1177/41.7.8515048
3. Alas S, Ng CP, Bonavida B (2002) Rituximab modifies the cisplatin-mitochondrial signaling pathway, resulting in apoptosis in cisplatin-resistant non-Hodgkin's lymphoma. Clin Cancer Res 8:836-845. http://clincancerres.aacrjournals.org/content/8/3/836 (Pubitemid 34742116)
4. Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A et al (2012) Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol 8:839-847. doi:10.1038/nchembio.1060
5. André N, Braguer D, Brasseur G, Gonçalves A, Lemesle-Meunier D, Guise S, Jordan MA, Briand C (2000) Paclitaxel induces release of cytochrome c from mitochondria isolated from human neuroblastoma cells. Cancer Res 60:5349-5353. http://cancerres.aacrjournals.org/content/60/19/ 5349
6. Angelucci A, Valentini A, Millimaggi D, Gravina GL, Miano R, Dolo V, Vicentini C, Bologna M, Federici G, Bernardini S (2006) Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways. Anticancer Drugs 17:1141-1150. doi:10.1097/01.cad.0000236302.89843.fc (Pubitemid 44673394)
7. Arce C, Pérez-Plasencia C, González-Fierro A, de la Cruz-Hernández E, Revilla-Vázquez A, Chávez-Blanco A, Trejo-Becerril C, Pérez-Cárdenas E, Taja-Chayeb L, Bargallo E et al (2006) A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS One 1:e98. doi:10.1371/journal.pone.0000098
8. Ardizzoni A, Addamo GF, Baldini E, Borghini U, Portalone L, De Marinis F, Lionetto R, Conte PF, Bruzzi P, Pennucci MC et al (1995) Mitomycin-ifosfamide- cisplatinum (MIP) vs MIP-interferon vs cisplatinum-carboplatin in metastatic non-smallcell lung cancer: a FONICAP randomised phase II study. Ital Lung Cancer Task Force Br J Cancer 71:115-119. doi:10.1038/bjc.1995.23
9. Arora A, Scholar EM (2005) Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther 315:971-979. doi:10.1124/jpet.105.084145 (Pubitemid 41635382)
10. Bai S, Nasse MW, Wang SH, Datta J, Kutay H, Yadav A, Nuovo G, Kumar P, Ghoshal K (2009) MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem 284(46):32015-32027. doi:10.1074/jbc.M109.016774
11. Baldo BA (2013) Adverse events to monoclonal antibodies used for cancer therapy: focus on hypersensitivity responses. Oncoimmunology 2:e26333. doi:10.4161/onci.26333
12. Barbone D, Cheung P, Battula S, Busacca S, Gray SG, Longley DB, Bueno R, Sugarbaker DJ, Fennell DA, Broaddus VC (2012) Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression. PLoS One 7:e52753. doi:10.1371/journal.pone.0052753
13. Barnes K, McIntosh E, Whetton AD, Daley GQ, Bentley J, Baldwin SA (2005) Chronic myeloid leukaemia: an investigation into the role of Bcr-Abl-induced abnormalities in glucose transport regulation. Oncogene 24:3257-3267. doi:10.1038/sj.onc.1208461 (Pubitemid 40695107)
14. Bilbro J, Mart M, Kyprianou M (2013) Therapeutic value of quinazoline-based compounds in prostate cancer. Anticancer Res 33:4695-4700
15. Blackburn C, Gigstad KM, Hales P, Garcia K, Jones M, Bruzzese FJ, Barrett C, Liu JX, Soucy TA, Sappal DS et al (2010) Characterization of a new series of non-covalent proteasome inhibitors with exquisite potency and selectivity for the 20S beta5-subunit. Biochem J 430:461-476. doi:10.1042/BJ20100383
16. Blaheta RA, Michaelis M, Driever PH, Cinatl J Jr (2005) Evolving anticancer drug valproic acid: insights into the mechanism and clinical studies. Med Res Rev 25:383-397. doi:10.1002/med.20027 (Pubitemid 40946533)
17. Blandino G, Valerio M, Cioce M, Mori F, Casadei L, Pulito C, Sacconi A, Biagioni F, Cortese G, Galanti S et al (2012) Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC. Nat Commun 29:865. doi:10.1038/ncomms1859
18. Boren J, Cascante M, Marin S, Comín-Anduix B, Centelles JJ, Lim S, Bassilian S, Ahmed S, Lee WN, Boros LG (2001) Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J Biol Chem 276:37747-37753. doi:10.1074/jbc.M105796200
19. Boros LG, Lee WN, Cascante M (2002) Imatinib and chronicphase leukemias. N Engl J Med 347:67-68. doi:10.1056/NEJM200207043470116
20. Braiteh F, Soriano AO, Garcia-Manero G, Hong D, Johnson MM, Silva LDP, Yang H, Alexander S, Wolff J, Kurzrock R (2008) Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Clin Cancer Res 14:6296-62301. doi:10.1158/1078-0432.CR-08-1247
21. Brower JV, Lim CH, Han C, Hankowski KE, Hamazaki T, Terada N (2009) Differential CpG island methylation of murine adenine nucleotide translocase genes. Biochim Biophys Acta 1789:198-203. doi:10.1016/j.bbagrm.2008.12.005
22. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, Roden M, Gnaiger E, Nohl H, Waldhäusl W, Fürnsinn C (2004) Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? Diabetes 53:1052-1059. doi:10.2337/diabetes.53.4. 1052 (Pubitemid 38436618)
23. Bugger H, Guzman C, Zechner C, Palmeri M, Russell KS, Russell RR 3rd (2011) Uncoupling protein downregulation in doxorubicin-induced heart failure improves mitochondrial coupling but increases reactive oxygen species generation. Cancer Chemother Pharmacol 67:1381-1388. doi:10.1007/s00280-010- 1441-7
24. Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, Viollet B, Thompson CB (2007) Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res 67:6745-6752. doi:10.1158/0008-5472.CAN-06-4447
25. Byczkowski JZ, Zychlinski L, Porter CW (1982) Potentiation of the antimitochondrial and antiproliferative effects of bis(guanylhydrazones) by phenethylbiguanide. Cancer Res 42:3592-3595. http://cancerres.aacrjournals.org/ content/42/9/3592 (Pubitemid 12054465)
26. Cairns RA, Papandreou I, Sutphin PD, Denko NC (2007) Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic chemotherapy. Proc Natl Acad Sci USA 104:9445-9450. doi:10.1073/pnas.0611662104 (Pubitemid 47185799)
27. Candi E, Agostini M, Melino M, Bernassola F (2014) How the TP53 family proteins TP63 and TP73 contribute to tumorigenesis: regulators and effectors. Hum Mutat doi:10.1002/humu.22523
28. Carvalho C, Correia S, Santos MS, Seiça R, Oliveira CR, Moreira PI (2008) Metformin promotes isolated rat liver mitochondria impairment. Mol Cell Biochem 308:75-83. doi:10.1007/s11010-007-9614-3 (Pubitemid 351167847)
29. Cecconi D, Donadelli M, Dalla Pozza E, Rinalducci S, Zolla L, Scupoli MT, Righetti PG, Scarpa A, Palmieri M (2009) Synergistic effect of trichostatin A and 5-aza-2′-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: a proteomic study. Proteomics 9:1952-1966. doi:10.1002/pmic.200701089
30. Chan A (2007) A review of the use of trastuzumab (Herceptin) plus vinorelbine in metastatic breast cancer. Ann Oncol 18:1152-1158. doi:10.1093/annonc/mdl476
31. Chan CL, Wu Z, Ciardelli T, Eastman A, Bresnick E (1993) Kinetic and DNA-binding properties of recombinant human O 6-methylguanine-DNA methyltransferase. Arch Biochem Biophys 300:193-200. doi:10.1006/abbi.1993.1027 (Pubitemid 23225736)
32. Chen Z, Li Y, Zhang H, Huang P, Luthra R (2010) Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29:4362-4368. doi:10.1038/onc.2010.193
33. Cherepanova NA, Minero AS, Rakhimova AR, Gromova ES (2011) Mechanism of CpG DNA methyltransferases M. SssI and Dnmt3a studied by DNA containing 2-aminopurine. Nucleosides, Nucleotides Nucleic Acids 30:619-631. doi:10.1080/15257770.2011.583973
34. Chesney J, Telang S (2013) Regulation of glycolytic and mitochondrial metabolism by ras. Curr Pharm Biotechnol 14:251-260. doi:10.2174/ 1389201011314030002
35. Cheung KJ, Gabrielson E, Werb Z, Ewald A (2013) Collective invasion in breast cancer requires a conserved basal epithelial program. Cell 155:1639-1651. doi:10.1016/j.cell.2013.11.029
36. Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, Woulfe K, Pravda E, Cassiola F, Desai J et al (2007) Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370:2011-2019. doi:10.1016/S0140-6736(07)61865-0 (Pubitemid 350236338)
37. Clark SJ, Melki J (2002) DNA methylation and gene silencing in cancer: which is the guilty party? Oncogene 21:5380-5387. doi:10.1038/sj.onc.1205598 (Pubitemid 34983474)
38. Coronel J, Cetina L, Pacheco I, Trejo-Becerril C, González-Fierro A, de la Cruz-Hernandez E, Perez-Cardenas E, Taja-Chayeb L, Arias-Bofill D, Candelaria M et al (2011) A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results. Med Oncol 28:S540-S546. doi:10.1007/s12032-010-9700-3
39. Cuéllar A, Escamilla E, Ramírez J, Chávez E (1984) Adriamycin as an inhibitor of 11 beta-hydroxylase activity in adrenal cortex mitochondria. Arch Biochem Biophys 235:538-543. doi:10.1016/0003-9861(84)90227-3
40. Cummings J, Spanswick VJ, Smyth JF (1995) Re-evaluation of the molecular pharmacology of mitomycin C. Eur J Cancer 31A:1928-1933. doi:10.1016/0959- 8049(95)00364-9 (Pubitemid 26023082)
41. Custódio JB, Cardoso CM, Almeida LM (2002) Thiol protecting agents and antioxidants inhibit the mitochondrial permeability transition promoted by etoposide: implications in the prevention of etoposide-induced apoptosis. Chem Biol Interact 140:169-184. doi:10.1016/S0009-2797(2)00020-0 (Pubitemid 34655538)
42. Dang CV, Le A, Gao P (2009) MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 15:6479-6483
43. Dao T, Yan S, Veomett N, Pankov D, Zhou L, Korontsvit T, Scott A, Whitten J, Maslak P, Casey E, et al (2013) Targeting the intracellular WT1 oncogene product with a therapeutic human antibody. Sci Transl Med 5:176ra33. doi:10.1126/scitranslmed.3005661
44. den Hollander P, Savage MI, Brown PH (2013) Targeted Therapy for Breast Cancer Prevention. Front Oncol 3:250. doi:10.1158/1078-0432.CR-09-0889
45. Ding Y, Liu Z, Desai S, Zhao Y, Liu H, Pannell LK, Yi H, Wright ER, Owen LB, Dean-Colomb W et al (2012) Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism. Nat Commun 3:1271. doi:10.1038/ncomms2236
46. Diotte NM, Xiong Y, Gao J, Chua BH, Ho YS (2009) Attenuation of doxorubicin-induced cardiac injury by mitochondrial glutaredoxin 2. Biochim Biophys Acta 1793:427-438. doi:10.1016/j.bbamcr.2008.10.014
47. Drahota Z, Palenickova E, Endlicher R, Milerova M, Brejchova J, Vosahlikova M, Svoboda P, Kazdova L, Kalous M, Cervinkova Z, Cahova M (2013) Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties. Physiol Res 63:1-11
48. Dykens JA, Jamieson J, Marroquin L, Nadanaciva S, Billis PA, Will Y (2008) Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro. Toxicol Appl Pharmacol 233:203-210. doi:10.1016/j.taap. 2008.08.013 (Pubitemid 50293339)
49. Eeva J, Nuutinen U, Ropponen A, Mättö M, Eray M, Pellinen R, Wahlfors J, Pelkonen J (2009) The involvement of mitochondria and the caspase-9 activation pathway in rituximab-induced apoptosis in FL cells. Apoptosis 14:687-698. doi:10.1007/s10495-009-0337-7
50. El-Mir MY, Nogueira V, Fontaine E, Avéret N, Rigoulet M, Leverve X (2000) Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 275:223-228. http://www.jbc.org/content/275/1/223 (Pubitemid 30038975)
51. Esteller M (2007) Epigenetics provides a new generation of oncogenes and tumour-suppressor genes. Br J Cancer 96:R26-R30. doi:10.1038/sj.bjc.6602918
52. Fabian MA, Biggs WH, Treiber DK, Atteridge CE, Azimioara MD, Benedetti MG, Carter TA, Ciceri P, Edeen PT, Floyd M et al (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 23:329-336. doi:10.1038/nbt1068 (Pubitemid 41094421)
53. Fantin VR, Berardi MJ, Babbe H, Michelman MV, Manning CM, Leder P (2005) A bifunctional targeted peptide that blocks HER-2 tyrosine kinase and disables mitochondrial function in HER-2-positive carcinoma cells. Cancer Res 65:6891-6900. http://cancerres.aacrjournals.org/content/65/15/6891 (Pubitemid 41060728)
54. Faure-Vigny H, Heddi A, Giraud S, Chautard D, Stepien G (1996) Expression of oxidative phosphorylation genes in renal tumors and tumoral cell lines. Mol Carcinog 16:165-172. doi:10.1002/(SICI)1098-2744(199607
55. Ferlini C, Raspaglio G, Mozzetti S, Distefano M, Filippetti F, Martinelli E, Ferrandina G, Gallo D, Ranelletti FO, Scambia G (2003) Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance. Mol Pharmacol 64:51-58. doi:10.1124/mol.64.1.51 (Pubitemid 36759817)
56. Fischer Y, Thomas J, Rösen P, Kammermeier H (1995) Action of metformin on glucose transport and glucose transporter GLUT1 and GLUT4 in heart muscle cells from healthy and diabetic rats. Endocrinology 136:412-420. doi:10.1210/endo.136.2.7835271
57. Fiume L, Manerba M, Vettraino M, Di Stefano G (2011) Effect of sorafenib on the energy metabolism of hepatocellular carcinoma cells. Eur J Pharmacol 670:39-43. doi:10.1016/j.ejphar.2011.08.038
58. Floridi A, D'Atri S, Bellocci M, Marcante ML, Paggi MG, Silvestrini B, Caputo A, De Martino C (1984) The effect of gossypol and Lonidamine on electron transport in Ehrlich ascites tumor mitochondria. Exp Mol Pathol 40:246-261. doi:10.1016/0014-4800(84)90081-9 (Pubitemid 14127606)
59. Funasaka T, Hogan V, Raz A (2009) Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer. Cancer Res 69:5349-5356. doi:10.1158/0008-5472.CAN-09-0488
60. Gallardo-Pérez JC, Rivero-Segura NA, Marín-Hernández A, Moreno-Sánchez R, Rodríguez-Enríques S (2014) GPI/AMF inhibition blocks the metastatic progression of mature multicellular tumor spheroids. Biochim Biophys Acta 1843:1043-1053. doi:10.1016/j.bbamcr.2014.01.013
61. Gaona-Gaona L, Molina-Jijón E, Tapia E, Zazueta C, Hernández-Pando R, Calderón-Oliver M, Zarco-Márquez G, Pinzón E, Pedraza-Chaverri J (2011) Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats. Toxicology 286:20-27. doi:10.1016/j.tox.2011.04.014
62. Garrido N, Pérez-Martos A, Faro M, Lou-Bonafonte JM, Fernández-Silva P, López-Pérez MJ, Montoya J, Enríquez JA (2008) Cisplatin-mediated impairment of mitochondrial DNA metabolism inversely correlates with glutathione levels. Biochem J 414:93-102. doi:10.1042/BJ20071615
63. 2+ in the toxicity of phenformin. Biochem Pharmacol 37:281-289. doi:10.1016/0006-2952(88)90730-7
64. Giacobbe A, Bongiorno-Borbone L, Bernassola F, Terrinoni A, Markert EK, Levine AJ, Feng Z, Agostini M, Zolla L, Agro AF, Notterman DA, Melino G, Peschiaroli A (2013) p63 regulates glutaminase 2 expression. Cell Cycle 12:1395-1405. doi:10.4161/cc.24478
65. Gillies RJ, Robey I, Gatenby RA (2008) Causes and consequences of increased glucose metabolism of cancers. J Nucl Med 49:24S-42S. doi:10.2967/jnumed.107.047258 (Pubitemid 351948035)
66. 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. doi:10.1158/1078-0432.CR- 04-0039 (Pubitemid 39346563)
67. Gowher H, Jeltsch A (2004) Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy. Cancer Biol Ther 3:1062-1068. doi:10.4161/cbt.3.11.1308 (Pubitemid 41350986)
68. Grazette LP, Boecker W, Matsui T, Semigran M, Force TL, Hajjar RJ, Rosenzweig A (2004) Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes: implications for herceptin-induced cardiomyopathy. J Am Coll Cardiol 44:2231-2238. doi:10.1016/j.jacc.2004.08.066 (Pubitemid 39576044)
69. Guerrero-Beltrán CE, Calderón-Oliver M, Martínez-Abundis E, Tapia E, Zarco-Márquez G, Zazueta C, Pedraza-Chaverri J (2010) Protective effect of sulforaphane against cisplatininduced mitochondrial alterations and impairment in the activity of NAD(P)H: quinone oxidoreductase 1 and γ glutamyl cysteine ligase: studies in mitochondria isolated from rat kidney and in LC-PK1 cells. Toxicol Lett 199:80-92. doi:10.1016/j.toxlet.2010.08.009
70. Guigas B, Detaille D, Chauvin C, Batandier C, De Oliveira F, Fontaine E, Leverve X (2004) Metformin inhibits mitochondrial permeability transition and cell death: a pharmacological in vitro study. Biochem J 382:877-884. doi:10.1042/BJ20040885 (Pubitemid 39312902)
71. Haas R, Stumpf DA, Parks JK, Eguren L (1981) Inhibitory effects of sodium valproate on oxidative phosphorylation. Neurology 31:1473-1476. doi:10.1212/WNL.31.11.1473 (Pubitemid 12228288)
72. Hamann A, Benecke H, Greten H, Hatthaei S (1993) Metformin increases glucose transporter protein and gene expression in human fibroblasts. Biochem Biophys Res Commun 196:382-387. doi:10.1006/bbcr.193.2260 (Pubitemid 23309519)
73. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ (2010) The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 9:325-338. doi:10.1038/nrd3003
74. Haynes BP, Dowsett M, Miller WR, Dixon JM, Bhatnagar AS (2003) The pharmacology of letrozole. J Steroid Biochem Mol Biol 87:35-45. doi:10.1016/S0960-0760(03)00384-4 (Pubitemid 37421337)
75. Hegde PS, Rusnak D, Bertiaux M, Alligood K, Strum J, Gagnon R, Gilmer TM (2007) Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles. Mol Cancer Ther 6:1629-1640. doi:10.1158/1535-7163.MCT-05-0399 (Pubitemid 46954030)
76. Hernández-Esquivel L, Marín-Hernández A, Pavón N, Carvajal K, Moreno-Sánchez R (2006) Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism. Toxicol Appl Pharmacol 212:79-88. doi:10.1016/j.taap.2005.06.023
77. Hickey FB, Cotter TG (2006) Identification of transcriptional targets associated with the expression of p210 Bcr-Abl. Eur J Haematol 76:369-383. doi:10.1111/j.1600-0609.2006.00629.x
78. Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H, Kinoshita T, Saito N, Ochiai A, Tomita M et al (2009) Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res 69:4918-4925. doi:10.1158/0008- 5472.CAN-08-4806
79. Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA (2010) Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol 148:3-15. doi:10.1016/j.jbiotec.2010.01.012
80. Hirschhaeuser F, Sattler UG, Mueller-Klieser W (2011) Lactate: a metabolic keyplayer in cancer. Cancer Res 71:6921-6925. doi:10.1158/0008-5472. CAN-11-1457
81. Höckel M, Vaupel P (2001) Biological consequences of tumor hypoxia. Semin Oncol 28:36-41. http://www.seminoncol.org/article/S0093-7754(01)90211-8/ abstract (Pubitemid 32522236)
82. Hodges-Gallagher L, Valentine CD, Bader SE, Kushner PJ (2007) Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells. Breast Cancer Res Treat 105:297-309. doi:10.1007/s10549-006-9459-6 (Pubitemid 47596448)
83. Iacobazzi V, Infantino V, Palmieri F (2008) Epigenetic mechanisms and Sp1 regulate mitochondrial citrate carrier gene expression. Biochem Biophys Res Commun 376:15-20. doi:10.1016/j.bbrc.2008.08.015
84. Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL, Merino M, Trepel J, Zbar B, Toro J, Ratcliffe PJ, Linehan WM, Neckers L (2005) HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 8:143-153. doi:10.1016/j.ccr.2005.06.017 (Pubitemid 41132743)
85. Kachadourian R, Brechbuhl HM, Ruiz-Azuara L, Gracia-Mora I, Day BJ (2010) Casiopeína IIgly-induced oxidative stress and mitochondrial dysfunction in human lung cancer A549 and H157 cells. Toxicology 268:176-183. doi:10.1016/j.tox.2009.12.010
86. Keller KE, Doctor ZM, Dwyer ZW, Lee YS (2014) SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells. Mol Cell 53:700-709. doi:10.1016/j.molcel.2014.02.015
87. Kessler T, Bayer M, Schwöppe C, Liersch R, Mesters RM, Berdel WE (2010) Compounds in clinical phase III and beyond. In: Liersch R, Berdel WE, Kessler T (eds) Angiogenesis inhibition. Springer, London, pp 137-163
88. Keunen O, Johansson M, Oudin A, Sanzey M, Rahim SA, Fack F, Thorsen F, Taxt T, Bartos M, Jirik R et al (2011) Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci USA 108:3749-3754. doi:10.1073/pnas.1014480108
89. Keyes SR, Heimbrook DC, Fracasso PM, Rockwell S, Sligar SG, Sartorelli AC (1985) Chemotherapeutic attack of hypoxic tumor cells by the bioreductive alkylating agent mitomycin C. Adv Enzyme Regul 23:291-307. doi:10.1016/0065- 2571(85)90053-6
90. Kibayashi M, Nagao M, Chiba S (1999) Influence of valproic acid on the expression of various acyl-CoA dehydrogenases in rats. Pediatr Int 41:52-60. doi:10.1046/j.1442-200x.1999.01012.x (Pubitemid 29268634)
91. Kim MJ, Kim DH, Jung WH, Koo JS (2014) Expression of metabolism-related proteins in triple-negative breast cancer. Int J Clin Exp Pathol 7:301-312. www.ijcep.com. ISSN 1936-2625/IJCEP1311042
92. Kita A, Mitsuoka K, Kaneko N, Nakata M, Yamanaka K, Jitsuoka M, Miyoshi S, Noda A, Mori M, Nakahara T, Sasamata M (2012) Sepantronium bromide (YM155) enhances response of human B-cell non-Hodgkin lymphoma to rituximab. J Pharmacol Exp Ther 343:178-183. doi:10.1124/jpet.112.195925
93. Klawitter J, Anderson N, Klawitter J, Christians U, Leibfritz D, Eckhardt SG, Serkova NJ (2009) Time-dependent effects of imatinib in human leukaemia cells: a kinetic NMR-profiling study. Br J Cancer 100:923-931. doi:10.1038/sj.bjc.6604946
94. Kluza J, Jendoubi M, Ballot C, Dammak A, Jonneaux A, Idziorek T, Joha S, Dauphin V, Malet-Martino M et al (2011) Exploiting mitochondrial dysfunction for effective elimination of imatinib-resistant leukemic cells. PLoS One 6:e21924. doi:10.1371/journal.pone.0021924
95. Koh MY, Spivak-Kroizman TR, Powis G (2010) HIF-1α and cancer therapy. In: Liersch R, Berdel WE, Kessler T (eds) Angiogenesis inhibition. Springer, London, pp 15-34
96. Kong M, Ba M, Liang H, Ma L, Yu Q, Yu T, Wang Y (2012) 5′-AzadC sensitizes paraquat toxic effects on PC12 cell. Neurosci Lett 524:35-39. doi:10.1016/j.neulet.2012.07.001
97. Ksienski D (2011) Imatinib mesylate: past successes and future challenges in the treatment of gastrointestinal stromal tumors. Clin Med Insights Oncol 5:365-379. doi:10.4137/CMO.S4259
98. Kunz-Schughart LA (1999) Multicellular tumor spheroids: intermediates between monolayer culture and in vivo tumor. Cell Biol Int 23:157-161. doi:10.1177/1087057104265040
99. Kunz-Schughart LA, Freyer JP, Hofstaedter F, Ebner R (2004) The use of 3-D cultures for high-throughput screening: the multicellular spheroid model. J Biomol Screen 9:228-273. doi:10.1177/1087057104265040
100. Lake DE, Hudis C (2002) Aromatase inhibitors in breast cancer: an update. Cancer Control 9:490-498. http://moffitt.org/File%20Library/Main%20Nav/ Research%20and%20Clinical%20Trials/Cancer%20Control%20Journal/v9n6/490.pdf (Pubitemid 35462554)
101. Le SB, Hailer MK, Buhrow S, Wang Q, Flatten K, Pediaditakis P, Bible KC, Lewis LD, Sausville EA, Pang YP, Ames MM et al (2007) Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity. J Biol Chem 282:8860-8872. doi:10.1074/jbc.M611777200 (Pubitemid 47093495)
102. Lee SJ, Wang JY (2009) Exploiting the promiscuity of imatinib. J Biol. 8:30. doi:10.1186/jbiol134
103. Lee CS, Park SY, Ko HH, Han ES (2004) Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells. Biochem Pharmacol 68:1857-1867. doi:10.1016/j.bcp.2004.06010 (Pubitemid 39278508)
104. Li GN, Wang SP, Xue X, Qu XJ, Liu HP (2013) Monoclonal antibody-related drugs for cancer therapy. Drug Discov Ther 7:178-184. doi:10.5582/ddt.2013.v7.5. 178
105. Lin YL, Meng Y, Jiang W, Roux B (2013) Explaining why Gleevec is a specific and potent inhibitor of Abl kinase. Proc Natl Acad Sci USA 110:1664-1669. doi:10.1073/pnas.1214330110
106. Liu W, Phang JM (2012) Proline dehydrogenase (oxidase), a mitochondrial tumor suppressor, and autophagy under the hypoxia microenvironment. Autophagy 8:1407-1409
107. Liu FT, Agrawal SG, Gribben JG, Ye H, Du MQ, Newland AC, Jia L (2008) Bortezomib blocks Bax degradation in malignant B cells during treatment with TRAIL. Blood 111:2797-2805
108. Liu W, Glunde K, Bhujwalla ZM, Raman V, Sharma A, Phang JM (2012) Proline oxidase promotes tumor cell survival in hypoxic tumor microenvironments. Cancer Res 72:3677-3686
109. Liu AM, Xu Z, Shek FH, Wong KF, Lee NP, Poon RT, Chen J, Luk JM (2014) miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma. PLoS ONE 9:e86872
110. Lu H, Li X, Luo Z, Liu J, Fan Z (2013) Cetuximab reverses the Warburg effect by inhibiting HIF-1-regulated LDH-A. Mol Cancer Ther 12:2187-2199. doi:10.1158/0008-5472.CAN-12-0080
111. Luwor RB, Lu Y, Li X, Mendelsohn J, Fan Z (2005) The antiepidermal growth factor receptor monoclonal antibody cetuximab/C225 reduces hypoxia-inducible factor-1 alpha, leading to transcriptional inhibition of vascular endothelial growth factor expression. Oncogene 24:4433-4441. doi:10.1038/sj.onc.1208625 (Pubitemid 40961766)
112. Ma W, Jacene H, Song D, Vilardell F, Messersmith WA, Laheru D, Wahl R, Endres C, Jimeno A, Pomper MG, Hidalgo M (2009) [18F]fluorodeoxyglucose positron emission tomography correlates with Akt pathway activity but is not predictive of clinical outcome during mTOR inhibitor therapy. J Clin Oncol 27:2697-2704. doi:10.1200/JCO.2008.18.8383
113. Mackay A, Urruticoechea A, Dixon JM, Dexter T, Fenwick K, Ashworth A, Drury S, Larionov A, Young O, White S et al (2007) Molecular response to aromatase inhibitor treatment in primary breast cancer. Breast Cancer Res 9:R37. doi:10.1186/bcr1732
114. Mandujano-Tinoco EA, Gallardo-Pérez JC, Marín- Hernández A, Moreno-Sánchez R, Rodríguez-Enríquez S (2013) Anti-mitochondrial therapy in human breast cáncer multicellular spheroids. Biochim Biophys Acta 1833:541-551. doi:10.1016/j.bbamcr.2012.11.013
115. 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. doi:10.1016/S0006-2952(03)00212-0
116. Marín-Hernández A, Rodríguez-Enríquez S, Vital-González PA, Flores-Rodríguez FL, Macías-Silva M, Sosa-Garrocho M, Moreno-Sánchez 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. doi:10.1111/j.1742-4658.2006.05214.x
117. Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ, Rodríguez-Enríquez S, Moreno-Sánchez R (2009) HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem 9:1084-1101. doi:10.2174/138955709788922610
118. Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S, Encalada R, Moreno-Sánchez R, Saavedra E (2011) Modeling cancer glycolysis. Biochim Biophys Acta 1807:755-767. doi:10.1016/j.bbabio.2010.11.006
119. Marín-Hernández A, Gallardo-Pérez JC, López-Ramírez SY, García-García JD, Rodríguez-Zavala JS, Ruiz-Ramírez L, Gracia-Mora I, Zentella-Dehesa A, Sosa-Garrocho M, Macías-Silva M, Moreno-Sánchez R, Rodríguez-Enríquez S (2012) Casiopeina II-gly and bromo-pyruvate inhibition of tumor hexokinase, glycolysis, and oxidative phosphorylation. Arch Toxicol 86:753-766. doi:10.1007/s00204-012-0809-3
120. Masdehors P, Merle-Béral H, Maloum K, Omura S, Magdelénat H, Delic J (2000) Deregulation of the ubiquitin system and p53 proteolysis modify the apoptotic response in B-CL lymphocytes. Blood 96:269-274. http://bloodjournal.hematologylibrary.org/content/96/1/269.long (Pubitemid 30456481)
121. Mathews EH, Liebenberg L, Pelzer R (2011) High-glycolytic cancers and their interplay with the body's glucose demand and supply cycle. Med Hypotheses 76:157-165. doi:10.1016/j.mehy.2010.09.006
122. Mazieres J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T et al (2013) Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 31:1997-2003. doi:10.1200/JCO.2012.45.6095
123. Mazurek S (2011) Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 43(2011):969-980
124. Mellor HR, Bell AR, Valentin JP, Roberts RR (2011) Cardiotoxicity associated with targeting kinase pathways in cancer. Toxicol Sci 120:14-32. doi:10.1093/toxsci/kfq378
125. Mendelsohn J, Baselga J (2000) The EGF receptor family as targets for cancer therapy. Oncogene 19:6550-6565. doi:10.1038/sj. onc.1204082
126. Meng F, Sun G, Zhong M, Yu Y, Brewer MA (2013) Anticancer efficacy of cisplatin and trichostatin A or 5-aza-2′-deoxycytidine on ovarian cancer. Br J Cancer 108:579-586. doi:10.1038/bjc.2013.10
127. Menon C, Polin GM, Prabakaran I, Hsi A, Cheung C, Culver JP, Pingpank JF, Sehgal CS, Yodh AG, Buerk DG et al (2003) An integrated approach to measuring tumor oxygen status using human melanoma xenografts as a model. Cancer Res 63:7232-7240. http://cancerres.aacrjournals.org/content/63/21/7232 (Pubitemid 37413462)
128. Miller WR, Larionov A (2011) Molecular effects of oestrogen deprivation in breast cancer. Mol Cell Endocrinol 340:127-136. doi:10.1097/FPC. 0b013e32820b853a
129. Miller WR, Larionov AA, Renshaw L, Anderson TJ, White S, Murray J, Murray E, Hampton G, Walker JR, Ho S et al (2007) Changes in breast cancer
130. Miller WR, Larionov A, Anderson TJ, Evans DB, Dixon JM (2012) Sequential changes in gene expression profiles in breast cancers during treatment with the aromatase inhibitor, letrozole. Pharmacogenomics J 12:10-21. doi:10.1038/tpj.2010.67
131. Miller MJ, Foy KC, Kaumaya PT (2013) Cancer immunotherapy: present status, future perspective, and a new paradigm of peptide immunotherapeutics. Discov Med 15:166-176. http://www.discoverymedicine.com/Megan-Jo-Miller/2013/03/ 28/cancer-immunotherapy-present-status-future-perspective-and-a-new-paradigm-of- peptide-immunotherapeutics/
132. 2+ release. J Biol Chem 280:715-721. doi:10.1074/jbc.M409819200
133. Montopoli M, Bellanda M, Lonardoni F, Ragazzi E, Dorigo P, Froldi G, Mammi S, Caparrotta L (2011) "Metabolic reprogramming"in ovarian cancer cells resistant to cisplatin. Curr Cancer Drug Targets 11:226-235. doi:10.2174/156800911794328501
134. Moreira PI, Custódio J, Moreno A, Oliveira CR, Santos MS (2006) Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure. J Biol Chem 281:10143-10152. doi:10.1074/jbc.M510249200 (Pubitemid 43864550)
135. Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A, Saavedra E (2007) Energy metabolism in tumor cells. FEBS J 274:1393-1418. doi:10.1111/j.1742-4658.2007.05686.x (Pubitemid 46333738)
136. Moreno-Sánchez R, Marín-Hernández A, Saavedra E, Pardo JP, Ralph SJ, Rodríguez-Enríquez S (2014) Who controls the ATP supply in cancer cells? Biochemistry lessons to understand cancer energy metabolism. Int J Biochem Cell Biol 2725:42-49. doi:10.1016/j.biocel.2014.01.025
137. Mrozek E, Kolesar J, Young D, Allen J, Villalona-Calero M, Shapiro CL (2008) Phase II study of sequentially administered low-dose mitomycin-C(MMC) and irinotecan (CPT-11) in women with metastatic breast cancer (MBC). Ann Oncol 19:1417-1422. doi:10.1093/annonc/mdn154
138. Müller 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. doi:10.1111/j.1432-1033.1986.tb10496.x (Pubitemid 17043851)
139. Nicolay K, Timmers RJ, Spoelstra E, Van der Neut R, Fok JJ, Huigen YM, Verkleij AJ, De Kruijff B (1984) The interaction of adriamycin with cardiolipin in model and rat liver mitochondrial membranes. Biochim Biophys Acta 778:359-371. doi:10.1016/0005-2736(84)90380-8 (Pubitemid 15180400)
140. Nowis D, Maczewski M, Mackiewicz U, Kujawa M, Ratajska A, Wieckowski MR, Wilczyński GM, Malinowska M, Bil J, Salwa P et al (2010) Cardiotoxicity of the anticancer therapeutic agent bortezomib. Am J Pathol 176:2658-2668. doi:10.2353/ajpath.2010.090690
141. Ott PA, Adams S (2011) Small-molecule protein kinase inhibitors and their effects on the immune system: implications for cancer treatment. Immunotherapy 3:213-227. doi:10.2217/imt.10.99
142. Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2002) Cytochrome c release from mitochondria proceeds by a twostep process. Proc Natl Acad Sci USA 99:1259-1263. doi:10.1073/pnas.241655498 (Pubitemid 34136480)
143. Owen MR, Doran E, Halestrap AP (2000) Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 348:607-614. doi:10.1042/0264-6021:3480607 (Pubitemid 30410251)
144. Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ (2012) Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 15:171-185. doi:10.1007/s10456-011- 9249-6
145. Papanikolaou V, Iliopoulos D, Dimou I, Dubos S, Kappas C, Kitsiou-Tzeli S, Tsezou A (2011) Survivin regulation by HER2 through NF-κB and c-myc in irradiated breast cancer cells. J Cell Mol Med 15:1542-1550. doi:10.1111/j.1582-4934.2010.01149.x
146. Park JH, Kim TH (2005) Release of cytochrome c from isolated mitochondria by etoposide. J Biochem Mol Biol 38:619-623. http://europepmc.org/abstract/MED/ 16202244
147. Patenaude A, Deschesnes RG, Rousseau JL, Petitclerc E, Lacroix J, Côté MF, C-Gaudreault R (2007) New soft alkylating agents with enhanced cytotoxicity against cancer cells resistant to chemotherapeutics and hypoxia. Cancer Res 67:2306-2316. doi:10.1158/0008-5472.CAN-06-3824 (Pubitemid 46424251)
148. Pathania D, Sechi M, Palomba M, Sanna V, Berretini F, Sias A, Taheri L, Neamati N (2014) Design and discovery of novel quinazolinedione-based redox modulators as therapies for pancreatic cancer. Biochim Biophys Acta 1840:332-343. doi:10.1016/j.bbagen.2013.08.005
149. Paz MM, Zhang X, Lu J, Holmgren A (2012) A new mechanism of action for the anticancer drug mitomycin C: mechanism-based inhibition of thioredoxin reductase. Chem Res Toxicol 25:1502-1511. doi:10.1021/tx3002065
150. Piperdi B, Ling YH, Liebes L, Muggia F, Perez-Soler R (2011) Bortezomib: understanding the mechanism of action. Mol Cancer Ther 10:2029-2030. doi:10.1158/1535-7163.MCT-11-0745
151. Polivka J Jr, Janku F (2014) Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther 142:164-175. doi:10.1016/j.pharmthera. 2013.12.004
152. Pollard PJ, Brière JJ, Alam NA, Barwell J, Barclay E, Wortham NC, Hunt T, Mitchell M, Olpin S, Moat SJ et al (2005) Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet 14:2231-2239. doi:10.1093/hmg/ ddi227 (Pubitemid 41418022)
153. Prenzel N, Fischer OM, Streit S, Hart S, Ullrich A (2001) The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer 8:11-31. doi:10.1677/erc.0.0080011 (Pubitemid 32520251)
154. Pritsos CA, Briggs LA, Gustafson DL (1997) A new cellular target for mitomycin C: a case for mitochondrial DNA. Oncol Res 9:333-337. http://www.biomedsearch.com/nih/ new-cellular-target-mitomycin-C/9406239.html (Pubitemid 127825987)
155. Qian W, Nishikawa M, Haque AM, Hirose M, Mashimo M, Sato E, Inoue M (2005) Mitochondrial density determines the cellular sensitivity to cisplatin-induced cell death. Am J Physiol Cell Physiol 289:C1466-C1475. doi:10.1152/ajpcell.00265.2005 (Pubitemid 41636351)
156. Radu M, Semenova G, Kosoff R, Chernoff J (2014) PAK signaling during the development and progression of cancer. Nat Rev Cancer 14:13-25. doi:10.1038/nrc3645
157. Rix U, Hantschel O, Dürnberger G, Remsing Rix L, Planyavsky M, Fernbach NV, Kaupe I, Bennett KL, Valent P, Colinge J, Köcher T, Superti-Furga G (2007) Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 110:4055-4063. doi:10.1182/blood-2007-07-102061 (Pubitemid 350248462)
158. Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2000) Distinct pathways for stimulation of cytochrome c release by etoposide. J Biol Chem 275:32438-32443. doi:10.1074/jbc.C000518200
159. 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. doi:10.1006/abbi.1999.1582
160. Rodríguez-Enríquez S, Vital-González PA, Flores-Rodríguez FL, Marín-Hernández A, Ruiz-Azuara L, Moreno-Sánchez R (2006) Control of celullar proliferation by modulation of oxidative phosphorylation in human and rodent fast-growing tumor cells. Toxicol Appl Pharmacol 215:208-217. doi:10.1016/j.taap.2006.02.005
161. Rodríguez-Enríquez S, Gallardo-Pérez JC, Avilés-Salas A, Marín-Hernández A, Carreño-Fuentes L, Maldonado-Lagunas V, Moreno-Sánchez R (2008) Energy metabolism transition in multi-cellular human tumor spheroids. J Cell Physiol 216:189-197. doi:10.1002/jcp.21392
162. Rodríguez-Enríquez S, Marín-Hernández A, Gallardo-Pérez JC, Car-reño-Fuentes L, Moreno-Sánchez R (2009) Targeting of cancer energy metabolism. Mol Nutr Food Res 53:29-48. doi:10.1002/mnfr.200700470
163. Rodríguez-Enríquez S, Carreño-Fuentes L, Gallardo-Pérez JC, Saavedra E, Quezada H, Vega A, Marín- Hernández A, Olín-Sandoval V, Torres-Márquez ME, Moreno-Sánchez R (2010) Oxidative phosphorylation is impaired by prolonged hypoxia in breast and possibly in cervix carcinoma. Int J Biochem Cell Biol 42:1744-1751. doi:10.1016/j.biocel.2010.07.010
164. Rodríguez-Enríquez S, Gallardo-Pérez JC, Marín-Hernández A, Aguilar-Ponce JL, Mandujano-Tinoco EA, Meneses A, Moreno-Sánchez R (2011) Oxidative phosphorylation as a target to arrest malignant neoplasias. Curr Med Chem 18:3156-3167. doi:10.2174/ 092986711796391561
165. Rolfe DF, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77:731-758. http://physrev.physiology.org/content/77/3/731.long (Pubitemid 27328739)
166. Rumbach L, Warter JM, Rendon A, Marescaux C, Micheletti G, Waksman A (1983) Inhibition of oxidative phosphorylation in hepatic and cerebral mitochondria of sodium valproate-treated rats. J Neurol Sci 61:417-423. doi:10.1016/0022-510X(83)90174-0
167. Saito T, Kaneko T (1968) Effects of simultaneous application of mitomycin C and prednisolone on respiration and glycolysis of Ehrlich ascites tumor cells in vitro. Tohoku J Exp Med 95:87-106. doi:10.1620/tjem.95.87
168. Sasaki M, Okamura M, Ideo A, Shimada J, Suzuki F, Ishihara M, Kikuchi H, Kanda Y, Kunii S, Sakagami H (2006) Re-evaluation of tumor-specific cytotoxicity of mitomycin C, bleomycin and peplomycin. Anticancer Res 26:3373-3380. doi:10.1126/scitranslmed.300765 (Pubitemid 44701511)
169. Schmelz K, Wagner M, Dörken B, Tamm I (2005) 5-Aza-2′- deoxycytidine induces p21WAF expression by demethylation of p73 leading to p53-independent apoptosis in myeloid leukemia. Int J Cancer 114:683-695. doi:10.1002/ijc.20797 (Pubitemid 40344429)
170. Schmidt H, Siems W, Müller M, Dumdey R, Rapoport SM (1991) ATP-producing and consuming processes of Ehrlich mouse ascites tumor cells in proliferating and resting phases. Exp Cell Res 94:122-127 (Pubitemid 121006256)
171. Schnekenburger M, Grandjenette C, Ghelfi J, Karius T, Foliguet B, Dicato M, Diederich M (2011) Sustained exposure to the DNA demethylating agent, 2′-deoxy-5-azacytidine, leads to apoptotic cell death in chronic myeloid leukemia by promoting differentiation, senescence, and autophagy. Biochem Pharmacol 81:364-378. doi:10.1016/0014-4827(91)90140-P
172. Sculier JP, Ghisdal L, Berghmans T, Branle F, Lafitte JJ, Vallot F, Meert AP, Lemaitre F, Steels E, Burniat A et al (2001) The role of mitomycin in the treatment of non-small cell lung cancer: a systematic review with meta-analysis of the literature. Br J Cancer 84:1150-1155. doi:10.1054/bjoc.2001.1742 (Pubitemid 32511330)
173. Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB, Gottlieb E (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7:77-85. doi:10.1016/j.ccr.2004.11.022 (Pubitemid 40126384)
174. Selimovic D, Porzig BB, El-Khattouti A, Badura HE, Ahmad M, Ghanjati F, Santourlidis S, Haikel Y, Hassan M (2013) Bortezomib/proteasome inhibitor triggers both apoptosis and autophagy-dependent pathways in melanoma cells. Cell Signal 25:308-318. doi:10.1016/j.cellsig.2012.10.004
175. Shah JJ, Kuhn DJ, Orlowski RZ (2009) Bortezomib and EGCG: no green tea for you? Blood 113:5695-5696. doi:10.1182/blood-2009-03-204776
176. Shin DY, Park YS, Yang K, Kim GY, Kim WJ, Han MH, Kang HS, Choi YH (2012) Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation. Int J Oncol 41:910-918. doi:10.3892/ijo.2012.1546
177. Silva MF, Ruiter JP, Illst L, Jakobs C, Duran M, de Almeida IT, Wanders RJ (1997) Valproate inhibits the mitochondrial pyruvatedriven oxidative phosphorylation in vitro. J Inherit Metab Dis 20:397-400. doi:10.1023/A: 1005398516208 (Pubitemid 27354625)
178. Singh KK, Russell J, Sigala B, Zhang Y, Williams J, Keshav KF (1999) Mitochondrial DNA determines the cellular response to cancer therapeutic agents. Oncogene 18:6641-6646. doi:10.1038/sj.onc.1203056
179. Song IS, Kim HK, Lee SR, Jeong SH, Kim N, Ko KS, Rhee BD, Han J (2013) Mitochondrial modulation decreases the bortezomib-resistance in multiple myeloma cells. Int J Cancer 133:1357-1367. doi:10.1002/ijc.28149
180. Sonveaux P, Végran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF et al (2008) Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 118:3930-3942. doi:10.1172/JCI36843
181. Spanswick VJ, Cummings J, Smyth JF (1996) Enzymology of mitomycin C metabolic activation in tumour tissue. Characterization of a novel mitochondrial reductase. Biochem Pharmacol 51:1623-1630. doi:10.1016/0006-2952(96)00104-9
182. Surendran S, Krishnamurthy V (2012) Effect of tanmoxifen on mitochondria-an in vitro study. Am J Pharmatech Res 2:471-482. http://www.ajptr.com/archive/volume-2/april-2012-issue-2/article-161.html
183. Sutherland RM (1988) Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 240:177-184. doi:10.1126/science.2451290
184. Sviriaeva IV, Ruuge EK, Shumaev KB (2007) Formation of superoxide radicals in isolated cardiac mitochondria: effect of adriamycin. Biofizika 52:1054-1059. doi:10.1134/S0006350910020119
185. Takai N, Kawamata N, Gui D, Said JW, Miyakawa I, Koeffler HP (2004) Human ovarian carcinoma cells: histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis. Cancer 101:2760-2770. doi:10.1002/cncr.20709 (Pubitemid 39603184)
186. Tamulevicius P, Streffer C (1995) Metabolic imaging in tumours by means of bioluminescence. Br J Cancer 72:1102-1112. doi:10.1038/bjc.1995.472
187. Tedder TF, Engel P (1994) CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today 15:450-454. doi:10.1016/0167-5699(94)90276-3 (Pubitemid 24272191)
188. Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordóñez Á, Corral-Escariz M, Soro I, López-Bernardo E, Perales-Clemente E et al (2011) Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting Complex I activity. Cell Metab 14:768-779. doi:10.1016/j.cmet.2011.10.008
189. Trojnar MK, Wierzchowska-Cioch E, Krzyzanowski M, Jargiełło M, Czuczwar SJ (2004) New generation of valproic acid. Pol J Pharmacol 56:283-288. http://www.if-pan.krakow.pl/pjp/pdf/2004/3-283.pdf (Pubitemid 39010762)
190. Tuquet C, Dupont J, Mesneau A, Roussaux J (2000) Effects of tamoxifen on the electron transport chain of isolated rat liver mitochondria. Cell Biol Toxicol 16:207-219. doi:10.1023/A:1007695308257
191. 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. http://cancerres.aacrjournals.org/content/49/23/6449 (Pubitemid 20008770)
192. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F (2012) Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) 122:253-270. doi:10.1042/CS20110386
193. Von Ahsen O, Waterhouse NJ, Kuwana T, Newmeyer DD, Green DR (2000) The 'harmless' release of cytochrome c. Cell Death Differ 7:1192-1199. http://www.nature.com/cdd/journal/v7/n12/pdf/4400782a.pdf (Pubitemid 32042226)
194. Waller CF (2010) Imatinib mesylate. Recent Results Cancer Res 184:3-20. doi:10.1007/978-3-642-01222-8-1
195. Wang M, Han XH, Zhang L, Yang J, Qian JF, Shi YK, Kwak LW, Romaguera J, Yi Q (2008) Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leukemia 22:179-185. doi:10.1038/sj.leu.2404959
196. Will Y, Dykens JA, Nadanaciva S, Hirakawa B, Jamieson J, Marroquin LD, Hynes J, Patyna S, Jessen BA (2008) Effect of the multitargeted tyrosine kinase inhibitors imatinib, dasatinib, sunitinib, and sorafenib on mitochondrial function in isolated rat heart mitochondria and H9c2 cells. Toxicol Sci 106:153-161. doi:10.1093/toxsci/kfn157
197. Williams SA, McConkey DJ (2003) The proteasome inhibitor bortezomib stabilizes a novel active form of p53 in human LNCaPPro5 prostate cancer cells. Cancer Res 63:7338-7344. http://cancerres.aacrjournals.org/content/63/21/7338 (Pubitemid 37413475)
198. Xu J, Zhou JY, Tainsky MA, Wu GS (2007) Evidence that tumor necrosis factor-related apoptosis-inducing ligand induction by 5-Aza-2́- deoxycytidine sensitizes human breast cancer cells to adriamycin. Cancer Res 67:1203-1211. doi:10.1158/0008-5472.CAN-06-2310
199. Xu J, Wang J, Xu B, Ge H, Zhou X, Fang JY (2013) Colorectal cancer cells refractory to anti-VEGF treatment are vulnerable to glycolytic blockade due to persistent impairment of mitochondria. Mol Cancer Ther 12:717-724. doi:10.1158/1535-7163.MCT-12-1016-T
200. Yang Z, Schumaker LM, Egorin MJ, Zuhowski EG, Guo Z, Cullen KJ (2006) Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mitochondrial membrane of head and neck squamous cell carcinoma: possible role in apoptosis. Clin Cancer Res 12:5817-5825. doi:10.1158/1078-0432.CR-06-1037
201. Yaromina A, Meyer S, Fabian C, Zaleska K, Sattler UG, Kunz-Schughart LA, Mueller-Klieser W, Zips D, Baumann M (2012) Effects of three modifiers of glycolysis on ATP, lactate, hypoxia, and growth in human tumor cell lines in vivo. Strahlenther Onkol 188:431-437. doi:10.1007/s00066-011-0054-3
202. Yin D, Zhou H, Kumagai T, Liu G, Ong JM, Black KL, Koeffler HP (2005) Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastoma multiforme (GBM). Oncogene 24:344-354. doi:10.1038/sj.onc.1208225 (Pubitemid 40188583)
203. Yu D, Hung MC (2000) Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene 19:6115-6121. doi:10.1038/sj.onc.1203972 (Pubitemid 32059461)
204. Zgouras D, Becker U, Loitsch S, Stein J (2004) Modulation of angiogenesis-related protein synthesis by valproic acid. Biochem Biophys Res Commun 316:693-697. doi:10.1016/j.bbrc.2004.02.105
205. Zhang D, Tai LK, Wong L, Chiu L, Sethi SK, Koay ES (2005) Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neupositive breast cancer. Mol Cell Proteomics 4:1686-1696. doi:10.1074/mcp.M400221-MCP200
206. Zhao F, Mancuso A, Bui TV, Tong X, Gruber JJ, Swider CR, Sanchez PV, Lum JJ, Sayed N, Melo JV et al (2010) Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1alpha-induced metabolic reprograming. Oncogene 29:2962-2972. doi:10.1038/onc.2010.67
207. Zhao Y, Liu H, Liu Z, Ding Y, Ledoux SP, Wilson GL, Voellmy R, Lin Y, Lin W, Nahta R, Liu B, Fodstad O, Chen J, Wu Y, Price JE, Tan M (2011) Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism. Cancer Res 71:4585-4597. doi:10.1158/0008-5472.CAN-11-0127
208. Zhao L, Ashek A, Wang L, Fang W, Dabral S, Dubois O, Cupitt J, Pullamsetti SS, Cotroneo E, Jones H et al (2013) Heterogeneity in lung (18)FDG uptake in pulmonary arterial hypertension: potential of dynamic (18)FDG positron emission tomography with kinetic analysis as a bridging biomarker for pulmonary vascular remodeling targeted treatments. Circulation 128:1214-1224. doi:10.1161/CIRCULATIONAHA.113.004136
209. Zsengellér ZK, Ellezian L, Brown D, Horváth B, Mukhopadhyay P, Kalyanaraman B, Parikh SM, Karumanchi SA, Stillman IE, Pacher P (2012) Cisplatin nephrotoxicity involves mitochondrial injury with impaired tubular mitochondrial enzyme activity. J Histochem Cytochem 60:521-529. doi:10.1369/0022155412446227
210. Zu XL, Guppy M (2004) Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun 313:459-465. doi:10.1016/j.bbrc.2003.11.136 (Pubitemid 38021849)