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Cancer Cell International
Published in: Cancer Cell International 1/2006

Open Access 01-12-2006 | Primary research

The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression

Authors: Anissa Belkaid, Jean-Christophe Currie, Julie Desgagnés, Borhane Annabi

Published in: Cancer Cell International | Issue 1/2006

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Abstract

Background

Chlorogenic acid (CHL), the most potent functional inhibitor of the microsomal glucose-6-phosphate translocase (G6PT), is thought to possess cancer chemopreventive properties. It is not known, however, whether any G6PT functions are involved in tumorigenesis. We investigated the effects of CHL and the potential role of G6PT in regulating the invasive phenotype of brain tumor-derived glioma cells.

Results

RT-PCR was used to show that, among the adult and pediatric brain tumor-derived cells tested, U-87 glioma cells expressed the highest levels of G6PT mRNA. U-87 cells lacked the microsomal catalytic subunit glucose-6-phosphatase (G6Pase)-α but expressed G6Pase-β which, when coupled to G6PT, allows G6P hydrolysis into glucose to occur in non-glyconeogenic tissues such as brain. CHL inhibited U-87 cell migration and matrix metalloproteinase (MMP)-2 secretion, two prerequisites for tumor cell invasion. Moreover, CHL also inhibited cell migration induced by sphingosine-1-phosphate (S1P), a potent mitogen for glioblastoma multiform cells, as well as the rapid, S1P-induced extracellular signal-regulated protein kinase phosphorylation potentially mediated through intracellular calcium mobilization, suggesting that G6PT may also perform crucial functions in regulating intracellular signalling. Overexpression of the recombinant G6PT protein induced U-87 glioma cell migration that was, in turn, antagonized by CHL. MMP-2 secretion was also inhibited by the adenosine triphosphate (ATP)-depleting agents 2-deoxyglucose and 5-thioglucose, a mechanism that may inhibit ATP-mediated calcium sequestration by G6PT.

Conclusion

We illustrate a new G6PT function in glioma cells that could regulate the intracellular signalling and invasive phenotype of brain tumor cells, and that can be targeted by the anticancer properties of CHL.
Appendix
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Literature
1.
Manach C, Scalbert A, Morand C, Remesy C, Jimenez L: Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004, 79: 727-747.PubMed
2.
Stoclet JC, Chataigneau T, Ndiaye M, Oak MH, El Bedoui J, Chataigneau M, Schini-Kerth VB: Vascular protection by dietary polyphenols. Eur J Pharmacol. 2004, 500: 299-313. 10.1016/j.ejphar.2004.07.034.CrossRefPubMed
3.
Scalbert A, Manach C, Morand C, Remesy C, Jimenez L: Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 2005, 45: 287-306. 10.1080/1040869059096.CrossRefPubMed
4.
Arts IC, Hollman PC: Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr. 2005, 81: 317S-325S.PubMed
5.
Block G, Patterson B, Subar A: Fruit, vegetables and cancer prevention: a review of the epidemiological evidence. Nutr Cancer. 1992, 18: 1-30.CrossRefPubMed
6.
Lambert JD, Hong J, Yang GY, Liao J, Yang CS: Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am J Clin Nutr. 2005, 81: 284S-291S.PubMed
7.
Kanadaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT, Lee MT: The antitumor activities of flavonoids. In Vivo. 2005, 19: 895-909.PubMed
8.
Roudebush P, Davenport DJ, Novotny BJ: The use of nutraceuticals in cancer therapy. Vet Clin North Am Small Anim Pract. 2004, 34: 249-269. 10.1016/j.cvsm.2003.09.001.CrossRefPubMed
9.
Zhu X, Chen B, Ma M, Luo X, Zhang F, Yao S, Wan Z, Yang D, Hang H: Simultaneous analysis of theanine, chlorogenic acid, purine alkaloids and catechins in tea samples with the help of multi-dimension information of on-line high performance liquid chromatography/electrospray-mass spectrometry. J Pharm Biomed Anal. 2004, 34: 695-704. 10.1016/S0731-7085(03)00605-8.CrossRefPubMed
10.
Moyers SB, Kumar NB: Green tea polyphenols and cancer chemoprevention: multiple mechanisms and endpoints for phase II trials. Nutr Rev. 2004, 62: 204-11. 10.1301/nr.2004.may.204-211.CrossRefPubMed
11.
Kazi A, Smith DM, Daniel K, Zhong S, Gupta P, Bosley ME, Dou QP: Potential molecular targets of tea polyphenols in human tumor cells: significance in cancer prevention. In Vivo. 2002, 16: 397-403.PubMed
12.
Mori H, Kawabata K, Matsunaga K, Ushida J, Fujii K, Hara A, Tanaka T, Murai H: Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis. Biofactors. 2000, 12: 101-105.CrossRefPubMed
13.
Chiang YM, Chuang DY, Wang SY, Kuo YH, Tsai PW, Shyur LF: Metabolite profiling and chemopreventive bioactivity of plant extracts from Bidens pilosa. J Ethnopharmacol. 2004, 95: 409-419. 10.1016/j.jep.2004.08.010.CrossRefPubMed
14.
Jin UH, Lee JY, Kang SK, Kim JK, Park WH, Kim JG, Moon SK, Kim CH: A phenolic compound, 5-caffeoylquinic acid (chlorogenic acid), is a new type and strong matrix metalloproteinase-9 inhibitor: isolation and identification from methanol extract of Euonymus alatus. Life Sci. 2005, 77: 2760-2769. 10.1016/j.lfs.2005.02.028.CrossRefPubMed
15.
Yen WJ, Wang BS, Chang LW, Duh PD: Antioxidant properties of roasted coffee residues. J Agric Food Chem. 2005, 53: 2658-2663. 10.1021/jf0402429.CrossRefPubMed
16.
Krakauer T: The polyphenol chlorogenic acid inhibits staphylococcal exotoxin-induced inflammatory cytokines and chemokines. Immunopharmacol Immunotoxicol. 2002, 24: 113-119. 10.1081/IPH-120003407.CrossRefPubMed
17.
Herling AW, Burger HJ, Schwab D, Hemmerle H, Below P, Schubert G: Pharmacodynamic profile of a novel inhibitor of the hepatic glucose-6-phosphatase system. Am J Physiol. 1998, 274: G1087-G1093.PubMed
18.
van Dijk TH, van der Sluijs FH, Wiegman CH, Baller JF, Gustafson LA, Burger HJ, Herling AW, Kuipers F, Meijer AJ, Reijngoud DJ: Acute inhibition of hepatic glucose-6-phosphatase does not affect gluconeogenesis but directs gluconeogenic flux toward glycogen in fasted rats. A pharmacological study with the chlorogenic acid derivative S4048. J Biol Chem. 2001, 276: 25727-25735. 10.1074/jbc.M101223200.CrossRefPubMed
19.
Bandsma RH, Wiegman CH, Herling AW, Burger HJ, ter Harmsel A, Meijer AJ, Romijn JA, Reijngoud DJ, Kuipers F: Acute inhibition of glucose-6-phosphate translocator activity leads to increased de novo lipogenesis and development of hepatic steatosis without affecting VLDL production in rats. Diabetes. 2001, 50: 2591-2597.CrossRefPubMed
20.
Hemmerle H, Burger HJ, Below P, Schubert G, Rippel R, Schindler PW, Paulus E, Herling AW: Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase. J Med Chem. 1997, 40: 137-145. 10.1021/jm9607360.CrossRefPubMed
21.
Arion WJ, Canfield WK, Ramos FC, Schindler PW, Burger HJ, Hemmerle H, Schubert G, Below P, Herling AW: Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose 6-phosphatase. Arch Biochem Biophys. 1997, 339: 315-322. 10.1006/abbi.1996.9874.CrossRefPubMed
22.
Leuzzi R, Banhegyi G, Kardon T, Marcolongo P, Capecchi PL, Burger HJ, Benedetti A, Fulceri R: Inhibition of microsomal glucose-6-phosphate transport in human neutrophils results in apoptosis: a potential explanation for neutrophil dysfunction in glycogen storage disease type 1b. Blood. 2003, 101: 2381-2387. 10.1182/blood-2002-08-2576.CrossRefPubMed
23.
Hiraiwa H, Pan CJ, Lin B, Moses SW, Chou JY: Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b. J Biol Chem. 1999, 274: 5532-5536. 10.1074/jbc.274.9.5532.CrossRefPubMed
24.
Calderwood S, Kilpatrick L, Douglas SD, Freedman M, Smith-Whitley K, Rolland M, Kurtzberg J: Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b. Blood. 2001, 97: 376-382. 10.1182/blood.V97.2.376.CrossRefPubMed
25.
Beaudet AL, Anderson DC, Michels VV, Arion WJ, Lange AJ: Neutropenia and impaired neutrophil migration in type IB glycogen storage disease. J Pediatr. 1980, 97: 906-910. 10.1016/S0022-3476(80)80418-5.CrossRefPubMed
26.
Kilpatrick L, Garty BZ, Lundquist KF, Hunter K, Stanley CA, Baker L, Douglas SD, Korchak HM: Impaired metabolic function and signalling defects in phagocytic cells in glycogen storage disease type 1b. J Clin Invest. 1990, 86: 196-202.PubMedCentralCrossRefPubMed
27.
Bashan N, Potashnik R, Peist A, Peleg N, Moran A, Moses SW: Deficient glucose phosphorylation as a possible common denominator and its relation to abnormal leucocyte function, in glycogen storage disease 1b patients. Eur J Pediatr. 1993, 152: S44-S48. 10.1007/BF02072087.CrossRefPubMed
28.
Korchak HM, Garty BZ, Stanley CA, Baker L, Douglas SD, Kilpatrick L: Impairment of calcium mobilization in phagocytic cells in glycogen storage disease type 1b. Eur J Pediatr. 1993, 152: S39-S43. 10.1007/BF02072086.CrossRefPubMed
29.
Potashnik R, Moran A, Moses SW, Peleg N, Bashan N: Hexose uptake and transport in polymorphonuclear leukocytes from patients with glycogen storage disease Ib. Pediatr Res. 1990, 28: 19-23.CrossRefPubMed
30.
Chen PY, Csutora P, Veyna-Burke NA, Marchase RB: Glucose-6-phosphate and Ca2+ sequestration are mutually enhanced in microsomes from liver, brain, and heart. Diabetes. 1998, 47: 874-881.CrossRefPubMed
31.
Arion WJ, Canfield WK, Ramos FC, Su ML, Burger HJ, Hemmerle H, Schubert G, Below P, Herling AW: Chlorogenic acid analogue S3483: a potent competitive inhibitor of the hepatic and renal glucose-6-phosphatase systems. Arch Biochem Biophys. 1998, 351: 279-285. 10.1006/abbi.1997.0563.CrossRefPubMed
32.
Ghosh A, Cheung YY, Mansfield BC, Chou JY: Brain contains a functional glucose-6-phosphatase complex capable of endogenous glucose production. J Biol Chem. 2005, 280: 11114-11119. 10.1074/jbc.M410894200.CrossRefPubMed
33.
Konishi Y, Kobayashi S: Transepithelial transport of chlorogenic acid, caffeic acid, and their colonic metabolites in intestinal caco-2 cell monolayers. J Agric Food Chem. 2004, 52: 2518-2526. 10.1021/jf035407c.CrossRefPubMed
34.
Annabi B, Lachambre MP, Bousquet-Gagnon N, Page M, Gingras D, Beliveau R: Green tea polyphenol (-)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells. Biochim Biophys Acta. 2002, 1542: 209-220. 10.1016/S0167-4889(01)00187-2.CrossRefPubMed
35.
Annabi B, Lachambre MP, Bousquet-Gagnon N, Page M, Gingras D, Beliveau R: Localization of membrane-type 1 matrix metalloproteinase in caveolae membrane domains. Biochem J. 2001, 353: 547-553. 10.1042/0264-6021:3530547.PubMedCentralCrossRefPubMed
36.
An J, Li Y, van De Werve G, Newgard CB: Overexpression of the P46 (T1) translocase component of the glucose-6-phosphatase complex in hepatocytes impairs glycogen accumulation via hydrolysis of glucose 1-phosphate. J Biol Chem. 2001, 276: 10722-10729. 10.1074/jbc.M009525200.CrossRefPubMed
37.
Edsall LC, Spiegel S: Enzymatic measurement of sphingosine-1-phosphate. Anal Biochem. 1999, 272: 80-86. 10.1006/abio.1999.4157.CrossRefPubMed
38.
Van Brocklyn JR, Letterle CA, Snyder PJ, Prior TW: Sphingosine-1-phosphate stimulates human glioma cell proliferation through Gi-coupled receptors: Role of ERK MAP kinase and phosphatidylinositol 3-kinase β. Cancer Lett. 2002, 181: 195-204. 10.1016/S0304-3835(02)00050-2.CrossRefPubMed
39.
Van Brocklyn JR, Young N, Roof R: Sphingosine-1-phosphate stimulates motility and invasiveness of human glioblastoma multiforme cells. Cancer Lett. 2003, 199: 53-60. 10.1016/S0304-3835(03)00334-3.CrossRefPubMed
40.
Young KW, Nahorski SR: Sphingosine 1-phosphate: a Ca2+ release mediator in the balance. Cell Calcium. Cell Calcium. 2002, 32: 335-341. 10.1016/S0143416002001835.CrossRefPubMed
41.
Gitzelmann R, Bosshard NU: Defective neutrophil and monocyte functions in glycogen storage disease type Ib: a literature review. Eur J Pediatr. 1993, 152: S33-S38. 10.1007/BF02072085.CrossRefPubMed
42.
Garty BZ, Douglas SD, Danon YL: Immune deficiency in glycogen storage disease type 1B. Isr J Med Sci. 1996, 32: 1276-1281.PubMed
43.
Chen LY, Shieh JJ, Lin B, Pan CJ, Gao JL, Murphy PM, Roe TF, Moses S, Ward JM, Lee EJ, Westphal H, Mansfield BC, Chou JY: Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter. Hum Mol Genet. 2003, 12: 2547-2558. 10.1093/hmg/ddg263.CrossRefPubMed
44.
Annabi B, Bouzeghrane M, Moumdjian R, Moghrabi A, Beliveau R: Probing the infiltrating character of brain tumors: inhibition of RhoA/ROK-mediated CD44 cell surface shedding from glioma cells by the green tea catechin EGCg. J Neurochem. 2005, 94: 906-916. 10.1111/j.1471-4159.2005.03256.x.CrossRefPubMed
45.
Baatout S, Jacquet P, Derradji H, Ooms D, Michaux A, Mergeay M: Study of the combined effect of X-irradiation and epigallocatechin-gallate (a tea component) on the growth inhibition and induction of apoptosis in human cancer cell lines. Oncol Rep. 2004, 12: 159-167.PubMed
46.
McLaughlin N, Annabi B, Bouzeghrane M, Temme A, Bahary JP, Moumdjian R, Béliveau R: The Survivin-mediated radioresistant phenotype of glioblastomas is regulated by RhoA and inhibited by the green tea polyphenol (-)-epigallocatechin-3-gallate. Brain Research. 2006, 1071: 1-9. 10.1016/j.brainres.2005.10.009.CrossRefPubMed
47.
Warburg O, Posener K, Negelein E: The metabolism of cancer cells. Biochem Zeitschr. 1934, 152: 129-169.
48.
Mathupala SP, Rempel A, Pedersen PL: Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem. 2001, 276: 43407-43412. 10.1074/jbc.M108181200.CrossRefPubMed
49.
Kostakoglu L, Hardoff R, Mirtcheva R, Goldsmith SJ: PET-CT fusion imaging in differentiating physiologic from pathologic FDG uptake. Radiographics. 2004, 24: 1411-1431.CrossRefPubMed
50.
Zingone A, Seidel J, Aloj L, Caraco C, Vaquero JJ, Jagoda EM, Chou JY, Green MV, Eckelman WC: Monitoring the correction of glycogen storage disease type 1a in a mouse model using [(18)F]FDG and a dedicated animal scanner. Life Sci. 2002, 71: 1293-1301. 10.1016/S0024-3205(02)01831-3.CrossRefPubMed
51.
Minn H, Kangas L, Knuutila V, Paul R, Sipila H: Determination of 2-fluoro-2-deoxy-D-glucose uptake and ATP level for evaluating drug effects in neoplastic cells. Res Exp Med (Berl). 1991, 191: 27-35.CrossRef
52.
Timperley WR: Glycolysis in neuroectodermal tumours. In: Thomas DGT, Graham DI, eds. Brain tumours. Scientific basis, clinical investigation and current therapy. 1980, London: Butterworth's, 145-167.
53.
Di Chiro G, Brooks RA, Patronas NJ, Bairamian D, Kornblith PL, Smith BH, Mansi L, Barker J: Issues in the in vivo measurement of glucose metabolism of human central nervous system tumors. Ann Neurol. 1984, 15: S138-S146. 10.1002/ana.410150727.CrossRefPubMed
54.
Padma MV, Said S, Jacobs M, Hwang DR, Dunigan K, Satter M, Christian B, Ruppert J, Bernstein T, Kraus G, Mantil JC: Prediction of pathology and survival by FDG PET in gliomas. J Neurooncol. 2003, 64: 227-237. 10.1023/A:1025665820001.CrossRefPubMed
55.
Dwarakanath BS, Jain VK: Modification of the radiation induced damage by 2-deoxy-D-glucose in organ cultures of human cerebral gliomas. Int J Radiat Oncol Biol Phys. 1987, 13: 741-746.CrossRefPubMed
56.
Woodward GE, Hudson MT: The effect of 2-desoxy-D-glucose on glycolysis and respiration of tumor and normal tissues. Cancer Res. 1954, 14: 599-605.PubMed
57.
Singh D, Banerji AK, Dwarakanath BS, Tripathi RP, Gupta JP, Mathew TL, Ravindranath T, Jain V: Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme. Strahlenther Onkol. 2005, 181: 507-514. 10.1007/s00066-005-1320-z.CrossRefPubMed
58.
Kang HT, Hwang ES: 2-Deoxyglucose: An anticancer and antiviral therapeutic, but not any more a low glucose mimetic. Life Sci. 2006, 78: 1392-1399. 10.1016/j.lfs.2005.07.001.CrossRefPubMed
59.
Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ, Huang P: Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 2005, 65: 613-621. 10.1158/0008-5472.CAN-04-4313.CrossRefPubMed
60.
Nicasio P, Aguilar-Santamaria L, Aranda E, Ortiz S, Gonzalez M: Hypoglycemic effect and chlorogenic acid content in two Cecropia species. Phytother Res. 2005, 19: 661-664. 10.1002/ptr.1722.CrossRefPubMed
61.
Hahn-Windgassen A, Nogueira V, Chen CC, Skeen JE, Sonenberg N, Hay N: Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem. 2005, 280: 32081-32089. 10.1074/jbc.M502876200.CrossRefPubMed
62.
Bandyopadhyay G, Biswas T, Roy KC, Mandal S, Mandal C, Pal BC, Bhattacharya S, Rakshit S, Bhattacharya DK, Chaudhuri U, Konar A, Bandyopadhyay S: Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase-dependent apoptosis in chronic myelogenous leukemic cells. Blood. 2004, 104: 2514-2522. 10.1182/blood-2003-11-4065.CrossRefPubMed
63.
Lee WC, Choi CH, Cha SH, Oh HL, Kim YK: Role of ERK in hydrogen peroxide-induced cell death of human glioma cells. Neurochem Res. 2005, 30: 263-270. 10.1007/s11064-005-2449-y.CrossRefPubMed
Metadata
Title
The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression
Authors
Anissa Belkaid
Jean-Christophe Currie
Julie Desgagnés
Borhane Annabi
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2006
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-6-7

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