Effect of polyphenols on glucose and lactate transport by breast cancer cells

Breast Cancer Research and Treatment

Volumn 157, Issue 1, 2016, Pages

  Martel, F ^a,b   Guedes, M ^a   Keating, E ^a,c  

^a University of Porto   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

^c UNIVERSITY OF PORTO   (Portugal)

Author keywords

Aerobic lactatogenesis; Breast cancer; Glucose transport; Lactate transport; Polyphenols

Indexed keywords

CHRYSIN; EPIGALLOCATECHIN GALLATE; GENISTEIN; GLUCOSE; GLUCOSE TRANSPORTER 1; GLUCOSE TRANSPORTER 4; HESPERETIN; KAEMPFEROL; LACTIC ACID; MONOCARBOXYLATE TRANSPORTER 1; MONOCARBOXYLATE TRANSPORTER 4; MYRICETIN; NARINGENIN; POLYPHENOL; QUERCETIN; RESVERATROL; XANTHOHUMOL; ANTINEOPLASTIC AGENT; COTRANSPORTER; MONOCARBOXYLATE TRANSPORT PROTEIN 1; MONOCARBOXYLATE TRANSPORTER; SLC2A1 PROTEIN, HUMAN;

ANTIANGIOGENIC ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; BREAST CANCER; BREAST CANCER CELL LINE; CANCER PREVENTION; CITRIC ACID CYCLE; COMPETITIVE INHIBITION; DRUG CYTOTOXICITY; DRUG STRUCTURE; GLUCOSE TRANSPORT; GLYCOLYSIS; HUMAN; INTRACELLULAR SIGNALING; LEWIS CARCINOMA; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; REVIEW; BREAST NEOPLASMS; DRUG EFFECTS; FEMALE; GENE EXPRESSION REGULATION; METABOLISM; TRANSPORT AT THE CELLULAR LEVEL; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; BIOLOGICAL TRANSPORT; BREAST NEOPLASMS; CELL LINE, TUMOR; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUCOSE; GLUCOSE TRANSPORTER TYPE 1; HUMANS; LACTIC ACID; MONOCARBOXYLIC ACID TRANSPORTERS; POLYPHENOLS; SYMPORTERS;

EID: 84964354502     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-016-3794-z     Document Type: Review

References (91)

1. Visioli F, Lastra CADL, Andres-Lacueva C, Aviram M, Calhau C, Cassano A, D’Archivio M, Faria A, Favé G, Fogliano V, Llorach R, Vitaglione P, Zoratti M, Edeas M (2011) Polyphenols and human health: a prospectus. Crit Rev Food Sci Nutr 51(6):524–546. doi:10.1080/10408391003698677
2. Thakur VS, Gupta K, Gupta S (2012) The chemopreventive and chemotherapeutic potentials of tea polyphenols. Curr Pharm Biotechnol 13(1):191–199. doi:10.2174/138920112798868584#sthash.2KlFWQ35.dpuf
3. Son TG, Camandola S, Mattson MP (2008) Hormetic dietary phytochemicals. NeuroMol Med 10(4):236–246. doi:10.1007/s12017-008-8037-y
4. Orena S, Owen J, Jin F, Fabian M, Gillitt ND, Zeisel SH (2015) Extracts of fruits and vegetables activate the antioxidant response element in IMR-32 cells. J Nutr 145(9):2006–2011. doi:10.3945/jn.115.216705
5. Vriend J, Reiter RJ (2015) The Keap1-Nrf2-antioxidant response element pathway: a review of its regulation by melatonin and the proteasome. Mol Cell Endocrinol 401:213–220. doi:10.1016/j.mce.2014.12.013
6. Upadhyay S, Dixit M (2015) Role of polyphenols and other phytochemicals on molecular signaling. Oxid Med Cell Longev 2015:504253. doi:10.1155/2015/504253
7. Izzi V, Masuelli L, Tresoldi I, Sacchetti P, Modesti A, Galvano F, Bei R (2012) The effects of dietary flavonoids on the regulation of redox inflammatory networks. Front Biosci (Landmark Ed) 17:2396–2418
8. Cojocneanu Petric R, Braicu C, Raduly L, Zanoaga O, Dragos N, Monroig P, Dumitrascu D, Berindan-Neagoe I (2015) Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers. OncoTargets Ther 8:2053–2066. doi:10.2147/ott.s83597
9. Szablewski L (2013) Expression of glucose transporters in cancers. Biochim Biophys Acta 1835(2):164–169. doi:10.1016/j.bbcan.2012.12.004
10. Wright EM, Loo DD, Hirayama BA (2011) Biology of human sodium glucose transporters. Physiol Rev 91(2):733–794. doi:10.1152/physrev.00055.2009
11. Wright EM, Turk E (2004) The sodium/glucose cotransport family SLC5. Pflugers Arch 447(5):510–518. doi:10.1007/s00424-003-1063-6
12. Birnbaum MJ, Haspel HC, Rosen OM (1986) Cloning and characterization of a cDNA encoding the rat brain glucose-transporter protein. Proc Natl Acad Sci USA 83(16):5784–5788
13. Zhang D, Li J, Wang F, Hu J, Wang S, Sun Y (2014) 2-Deoxy-d-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Lett 355(2):176–183. doi:10.1016/j.canlet.2014.09.003
14. Ortega AD, Sanchez-Arago M, Giner-Sanchez D, Sanchez-Cenizo L, Willers I, Cuezva JM (2009) Glucose avidity of carcinomas. Cancer Lett 276(2):125–135. doi:10.1016/j.canlet.2008.08.007
15. Dhup S, Dadhich RK, Porporato PE, Sonveaux P (2012) Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis. Curr Pharm Des 18(10):1319–1330. doi:10.2174/138161212799504902
16. Lieberman M, Marks A (2009) Generation of ATP from glucose: glycolysis. In: Marks’ basic medical biochemistry: a clinical approach, 3rd edn. Lippincoyt Williams and Wilkins, Philadelphia, pp 402–417
17. Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314
18. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013
19. 2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J 418(1):29–37. doi:10.1042/BJ20081258
20. Ganapathy V, Thangaraju M, Prasad PD (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121(1):29–40. doi:10.1016/j.pharmthera.2008.09.005
21. Macheda ML, Rogers S, Best JD (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202(3):654–662. doi:10.1002/jcp.20166
22. Pinheiro C, Sousa B, Albergaria A, Paredes J, Dufloth R, Vieira D, Schmitt F, Baltazar F (2011) GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. Histol Histopathol 26(10):1279–1286
23. Rodriguez-Enriquez S, Marin-Hernandez A, Gallardo-Perez JC, Carreno-Fuentes L, Moreno-Sanchez R (2009) Targeting of cancer energy metabolism. Mol Nutr Food Res 53(1):29–48. doi:10.1002/mnfr.200700470
24. Medina RA, Owen GI (2002) Glucose transporters: expression, regulation and cancer. Biol Res 35(1):9–26
25. Furuta E, Okuda H, Kobayashi A, Watabe K (2010) Metabolic genes in cancer: their roles in tumor progression and clinical implications. Biochim Biophys Acta 1805(2):141–152. doi:10.1016/j.bbcan.2010.01.005
26. Lopez-Lazaro M (2008) The warburg effect: why and how do cancer cells activate glycolysis in the presence of oxygen? Anticancer Agents Med Chem 8(3):305–312. doi:10.2174/187152008783961932#sthash.5ri1yR5h.dpuf
27. Grover-McKay M, Walsh SA, Seftor EA, Thomas PA, Hendrix MJ (1998) Role for glucose transporter 1 protein in human breast cancer. Pathol Oncol Res 4(2):115–120
28. Krzeslak A, Wojcik-Krowiranda K, Forma E, Jozwiak P, Romanowicz H, Bienkiewicz A, Brys M (2012) Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol Oncol Res 18(3):721–728. doi:10.1007/s12253-012-9500-5
29. Zamora-Leon SP, Golde DW, Concha II, Rivas CI, Delgado-Lopez F, Baselga J, Nualart F, Vera JC (1996) Expression of the fructose transporter GLUT5 in human breast cancer. Proc Natl Acad Sci USA 93(5):1847–1852
30. Stackhouse BL, Williams H, Berry P, Russell G, Thompson P, Winter JL, Kute T (2005) Measurement of glut-1 expression using tissue microarrays to determine a race specific prognostic marker for breast cancer. Breast Cancer Res Treat 93(3):247–253. doi:10.1007/s10549-005-5158-y
31. Guedes M, Araujo JR, Correia-Branco A, Gregorio I, Martel F, Keating E (2016) Modulation of the uptake of critical nutrients by breast cancer cells by lactate: impact on cell survival, proliferation and migration. Exp Cell Res. doi:10.1016/j.yexcr.2016.01.008
32. Harmon AW, Patel YM (2004) Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: a mechanism for impaired cellular proliferation. Breast Cancer Res Treat 85(2):103–110. doi:10.1023/B:BREA.0000025397.56192.e2
33. Moreira L, Araujo I, Costa T, Correia-Branco A, Faria A, Martel F, Keating E (2013) Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism. Exp Cell Res 319(12):1784–1795. doi:10.1016/j.yexcr.2013.05.001
34. Garrido P, Moran J, Alonso A, Gonzalez S, Gonzalez C (2013) 17beta-estradiol activates glucose uptake via GLUT4 translocation and PI3 K/Akt signaling pathway in MCF-7 cells. Endocrinology 154(6):1979–1989. doi:10.1210/en.2012-1558
35. Medina RA, Meneses AM, Vera JC, Guzman C, Nualart F, Astuya A, Garcia MA, Kato S, Carvajal A, Pinto M, Owen GI (2003) Estrogen and progesterone up-regulate glucose transporter expression in ZR-75-1 human breast cancer cells. Endocrinology 144(10):4527–4535. doi:10.1210/en.2003-0294
36. Yang Y, Wolfram J, Boom K, Fang X, Shen H, Ferrari M (2013) Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells. Cell Biochem Funct 31(5):374–379. doi:10.1002/cbf.2905
37. Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair BG, Lin C, Peters BA, Velculescu VE, Park BH (2004) The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther 3(8):772–775
38. Knobbe CB, Merlo A, Reifenberger G (2002) Pten signaling in gliomas. Neuro-Oncology 4(3):196–211. doi:10.1093/neuonc/4.3.196
39. Pedrero JM, Carracedo DG, Pinto CM, Zapatero AH, Rodrigo JP, Nieto CS, Gonzalez MV (2005) Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma. Int J Cancer 114(2):242–248. doi:10.1002/ijc.20711
40. Yang L, Wu X, Wang Y, Zhang K, Wu J, Yuan YC, Deng X, Chen L, Kim CC, Lau S, Somlo G, Yen Y (2011) FZD7 has a critical role in cell proliferation in triple negative breast cancer. Oncogene 30(43):4437–4446. doi:10.1038/onc.2011.145
41. Garrido P, Osorio FG, Moran J, Cabello E, Alonso A, Freije JM, Gonzalez C (2015) Loss of GLUT4 induces metabolic reprogramming and impairs viability of breast cancer cells. J Cell Physiol 230(1):191–198. doi:10.1002/jcp.24698
42. Purcell SH, Aerni-Flessner LB, Willcockson AR, Diggs-Andrews KA, Fisher SJ, Moley KH (2011) Improved insulin sensitivity by GLUT12 overexpression in mice. Diabetes 60(5):1478–1482. doi:10.2337/db11-0033
43. Stuart CA, Howell ME, Zhang Y, Yin D (2009) Insulin-stimulated translocation of glucose transporter (GLUT) 12 parallels that of GLUT4 in normal muscle. J Clin Endocrinol Metab 94(9):3535–3542. doi:10.1210/jc.2009-0162
44. Rogers S, Macheda ML, Docherty SE, Carty MD, Henderson MA, Soeller WC, Gibbs EM, James DE, Best JD (2002) Identification of a novel glucose transporter-like protein-GLUT-12. Am J Physiol Endocrinol Metab 282(3):E733–E738
45. Martel F, Monteiro R, Calhau C (2010) Effect of polyphenols on the intestinal and placental transport of some bioactive compounds. Nutr Res Rev 23(1):47–64. doi:10.1017/s0954422410000053
46. 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(21):6936–6943
47. Kanwar U, Kaur R, Chadha S, Sanyal S (1990) Gossypol-induced inhibition of glucose uptake in human ejaculated spermatozoa may be mediated by lipid peroxidation. Contraception 42(5):573–587
48. Nakamura M, Ikeda M, Okinaga S, Arai K (1988) Metabolism of round spermatids in the rat: effect of gossypol on the glucose transport. Andrologia 20(5):411–416
49. Perez A, Ojeda P, Valenzuela X, Ortega M, Sanchez C, Ojeda L, Castro M, Carcamo JG, Rauch MC, Concha II, Rivas CI, Vera JC, Reyes AM (2009) Endofacial competitive inhibition of the glucose transporter 1 activity by gossypol. Am J Physiol Cell Physiol 297(1):C86–C93. doi:10.1152/ajpcell.00501.2008
50. Lim HA, Kim JH, Kim JH, Sung MK, Kim MK, Park JH, Kim JS (2006) Genistein induces glucose-regulated protein 78 in mammary tumor cells. J Med Food 9(1):28–32. doi:10.1089/jmf.2006.9.28
51. Jung KH, Lee JH, Thien Quach CH, Paik JY, Oh H, Park JW, Lee EJ, Moon SH, Lee KH (2013) Resveratrol suppresses cancer cell glucose uptake by targeting reactive oxygen species-mediated hypoxia-inducible factor-1alpha activation. J Nucl Med 54(12):2161–2167. doi:10.2967/jnumed.112.115436
52. Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, Vescovi PP, Fogliano V, Marchelli R (2005) Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res 49(5):495–504. doi:10.1002/mnfr.200500002
53. Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE (2007) Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomark Prev 16(6):1246–1252. doi:10.1158/1055-9965.EPI-07-0022
54. Azevedo C, Correia-Branco A, Araujo JR, Guimaraes JT, Keating E, Martel F (2015) The chemopreventive effect of the dietary compound kaempferol on the MCF-7 human breast cancer cell line is dependent on inhibition of glucose cellular uptake. Nutr Cancer 67(3):504–513. doi:10.1080/01635581.2015.1002625
55. Hernandez JF, Uruena CP, Cifuentes MC, Sandoval TA, Pombo LM, Castaneda D, Asea A, Fiorentino S (2014) A Petiveria alliacea standardized fraction induces breast adenocarcinoma cell death by modulating glycolytic metabolism. J Ethnopharmacol 153(3):641–649. doi:10.1016/j.jep.2014.03.013
56. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4(11):891–899. doi:10.1038/nrc1478
57. Webb BA, Chimenti M, Jacobson MP, Barber DL (2011) Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 11(9):671–677. doi:10.1038/nrc3110
58. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, Renner K, Timischl B, Mackensen A, Kunz-Schughart L, Andreesen R, Krause SW, Kreutz M (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109(9):3812–3819. doi:10.1182/blood-2006-07-035972
59. Icard P, Lincet H (2012) A global view of the biochemical pathways involved in the regulation of the metabolism of cancer cells. Biochim Biophys Acta 1826(2):423–433. doi:10.1016/j.bbcan.2012.07.001
60. Lu H, Forbes RA, Verma A (2002) Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem 277(26):23111–23115. doi:10.1074/jbc.M202487200
61. Beckert S, Farrahi F, Aslam RS, Scheuenstuhl H, Königsrainer A, Hussain MZ, Hunt TK (2006) Lactate stimulates endothelial cell migration. Wound Repair Regen 14(3):321–324. doi:10.1111/j.1743-6109.2006.00127.x
62. Halestrap AP, Price NT (1999) The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343(Pt 2):281–299
63. Wilson MC, Meredith D, Fox JEM, Manoharan C, Davies AJ, Halestrap AP (2005) Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4—the ancillary protein for the insensitive MCT2 is embigin (gp70). J Biol Chem 280(29):27213–27221. doi:10.1074/jbc.M411950200
64. Dimmer KS, Friedrich B, Lang F, Deitmer JW, Bröer S (2000) The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J 350(1):219–227. doi:10.1042/bj3500219
65. Ullah MS, Davies AJ, Halestrap AP (2006) The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1 alpha-dependent mechanism. J Biol Chem 281(14):9030–9037. doi:10.1074/jbc.M511397200
66. Halestrap AP (2013) The SLC16 gene family—structure, role and regulation in health and disease. Mol Aspects Med 34(2–3):337–349. doi:10.1016/j.mam.2012.05.003
67. Halestrap AP, Meredith D (2004) The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447(5):619–628. doi:10.1007/s00424-003-1067-2
68. Colen CB, Seraji-Bozorgzad N, Marples B, Galloway MP, Sloan AE, Mathupala SP (2006) Metabolic remodeling of malignant gliomas for enhanced sensitization during radiotherapy: an in vitro study. Neurosurgery 59(6):1313–1323. doi:10.1227/01.NEU.0000249218.65332.BF(discussion 1323–1324)
69. Colen CB, Shen Y, Ghoddoussi F, Yu P, Francis TB, Koch BJ, Monterey MD, Galloway MP, Sloan AE, Mathupala SP (2011) Metabolic targeting of lactate efflux by malignant glioma inhibits invasiveness and induces necrosis: an in vivo study. Neoplasia 13(7):620–632
70. Jones NP, Schulze A (2012) Targeting cancer metabolism—aiming at a tumour’s sweet-spot. Drug Discov Today 17(5–6):232–241. doi:10.1016/j.drudis.2011.12.017
71. Mathupala SP, Colen CB, Parajuli P, Sloan AE (2007) Lactate and malignant tumors: a therapeutic target at the end stage of glycolysis. J Bioenerg Biomembr 39(1):73–77. doi:10.1007/s10863-006-9062-x
72. Mathupala SP, Parajuli P, Sloan AE (2004) Silencing of monocarboxylate transporters via small interfering ribonucleic acid inhibits glycolysis and induces cell death in malignant glioma: an in vitro study. Neurosurgery 55(6):1410–1419. doi:10.1227/01.NEU.0000143034.62913.59(discussion 1419)
73. Sonveaux P, Végran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, Kelley MJ, Gallez B, Wahl ML, Feron O, Dewhirst MW (2008) Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Investig 118(12):3930–3942. doi:10.1172/JCI36843
74. Fang J, Quinones QJ, Holman TL, Morowitz MJ, Wang Q, Zhao H, Sivo F, Maris JM, Wahl ML (2006) The H + -linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma. Mol Pharmacol 70(6):2108–2115. doi:10.1124/mol.106.026245
75. Koukourakis MI, Giatromanolaki A, Bougioukas G, Sivridis E (2007) Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma. Cancer Biol Ther 6(9):1476–1479
76. Koukourakis MI, Giatromanolaki A, Harris AL, Sivridis E (2006) Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res 66(2):632–637. doi:10.1158/0008-5472.can-05-3260
77. Pinheiro C, Albergaria A, Paredes J, Sousa B, Dufloth R, Vieira D, Schmitt F, Baltazar F (2010) Monocarboxylate transporter 1 is up-regulated in basal-like breast carcinoma. Histopathology 56(7):860–867. doi:10.1111/j.1365-2559.2010.03560.x
78. Pinheiro C, Longatto-Filho A, Azevedo-Silva J, Casal M, Schmitt FC, Baltazar F (2012) Role of monocarboxylate transporters in human cancers: state of the art. J Bioenerg Biomembr 44(1):127–139. doi:10.1007/s10863-012-9428-1
79. Pinheiro C, Longatto-Filho A, Ferreira L, Pereira SM, Etlinger D, Moreira MA, Jube LF, Queiroz GS, Schmitt F, Baltazar F (2008) Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma. Int J Gynecol Pathol 27(4):568–574. doi:10.1097/PGP.0b013e31817b5b40
80. Pinheiro C, Longatto-Filho A, Scapulatempo C, Ferreira L, Martins S, Pellerin L, Rodrigues M, Alves VA, Schmitt F, Baltazar F (2008) Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch 452(2):139–146. doi:10.1007/s00428-007-0558-5
81. Pinheiro C, Longatto-Filho A, Simoes K, Jacob CE, Bresciani CJ, Zilberstein B, Cecconello I, Alves VA, Schmitt F, Baltazar F (2009) The prognostic value of CD147/EMMPRIN is associated with monocarboxylate transporter 1 co-expression in gastric cancer. Eur J Cancer 45(13):2418–2424. doi:10.1016/j.ejca.2009.06.018
82. de Oliveira AT, Pinheiro C, Longatto-Filho A, Brito MJ, Martinho O, Matos D, Carvalho AL, Vazquez VL, Silva TB, Scapulatempo C, Saad SS, Reis RM, Baltazar F (2012) Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147) is associated with low survival in patients with gastrointestinal stromal tumors (GISTs). J Bioenerg Biomembr 44(1):171–178. doi:10.1007/s10863-012-9408-5
83. Baltazar F, Pinheiro C, Morais-Santos F, Azevedo-Silva J, Queiros O, Preto A, Casal M (2014) Monocarboxylate transporters as targets and mediators in cancer therapy response. Histol Histopathol 29(12):1511–1524. doi:10.14670/HH-29.1511
84. Morais-Santos F, Miranda-Goncalves V, Pinheiro S, Vieira AF, Paredes J, Schmitt FC, Baltazar F, Pinheiro C (2014) Differential sensitivities to lactate transport inhibitors of breast cancer cell lines. Endocr Relat Cancer 21(1):27–38. doi:10.1530/erc-13-0132
85. Morais-Santos F, Granja S, Miranda-Goncalves V, Moreira AH, Queiros S, Vilaca JL, Schmitt FC, Longatto-Filho A, Paredes J, Baltazar F, Pinheiro C (2015) Targeting lactate transport suppresses in vivo breast tumour growth. Oncotarget 6(22):19177–19189. doi:10.18632/oncotarget.3910
86. Kim JH, Kim SH, Alfieri AA, Young CW (1984) Quercetin, an inhibitor of lactate transport and a hyperthermic sensitizer of HeLa cells. Cancer Res 44(1):102–106
87. Volk C, Kempski B, Kempski OS (1997) Inhibition of lactate export by quercetin acidifies rat glial cells in vitro. Neurosci Lett 223(2):121–124. doi:10.1016/S0304-3940(97)13420-6
88. Wang Q, Morris ME (2007) Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Drug Metab Dispos 35(2):201–208. doi:10.1124/dmd.106.012369
89. Hong CS, Graham NA, Gu W, Espindola Camacho C, Mah V, Maresh EL, Alavi M, Bagryanova L, Krotee PA, Gardner BK, Behbahan IS, Horvath S, Chia D, Mellinghoff IK, Hurvitz SA, Dubinett SM, Critchlow SE, Kurdistani SK, Goodglick L, Braas D, Graeber TG, Christofk HR (2016) MCT1 modulates cancer cell pyruvate export and growth of tumors that co-express MCT1 and MCT4. Cell Rep 14(7):1590–1601. doi:10.1016/j.celrep.2016.01.057
90. Harris T, Eliyahu G, Frydman L, Degani H (2009) Kinetics of hyperpolarized 13C1-pyruvate transport and metabolism in living human breast cancer cells. Proc Natl Acad Sci USA 106(43):18131–18136. doi:10.1073/pnas.0909049106
91. Negrão R, Faria A (2009) Natural polyphenols as anti-oxidant, anti-inflammatory and anti-angiogenic agents in the metabolic syndrome. In: Soares R, Costa C (eds) Oxidative stress, inflammation and angiogenesis in the metabolic syndrome, 1st edn. Springer, Dordrecht, pp 147–180