Skip to main content
SpringerLink
Log in

Influence of Serum and Hypoxia on Incorporation of [14C]-d-Glucose or [14C]-l-Glutamine into Lipids and Lactate in Murine Glioblastoma Cells

  • Original Article
  • Published:
Lipids

Abstract

Glucose and glutamine are essential energy metabolites for brain tumor growth and survival under both normoxic and hypoxic conditions. Both metabolites can contribute their carbons to lipid biosynthesis. We used uniformly labeled [14C]-U-d-glucose and [14C]-U-l-glutamine to examine the profile of de novo lipid biosynthesis in the VM-M3 murine glioblastoma cells. The major lipids synthesized included phosphatidylcholine (PtdCho), phosphatidylethanolamine (EtnGpl), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer), sphingomyelin (CerPCho), bis(monoacylglycero)phosphate (BMP)/phosphatidic acid (PtdOH), cholesterol (C), cardiolipin (Ptd2Gro), and gangliosides. Endogenous lipid synthesis, using either glucose or glutamine, was greater in media without fetal bovine serum (FBS) than in media containing 10 % FBS under normoxia. De novo lipid synthesis was greater using glucose carbons than glutamine carbons under normoxia. The reverse was observed for most lipids under hypoxia suggesting an attenuation of glucose entering the TCA cycle. Lactate was produced largely from glucose carbons with minimal lactate derived from glutamine under either normoxia or hypoxia. Accumulation of triacylglycerols (TAG), containing mostly saturated and mono-unsaturated fatty acids, was observed under hypoxia using carbons from either glucose or glutamine. The data show that the incorporation of labeled glucose and glutamine into most synthesized lipids was dependent on the type of growth environment, and that the VM-M3 glioblastoma cells could acquire lipids, especially cholesterol, from the external environment for growth and proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

AA:

Antimycin A

ACLY:

ATP citrate lyase

ACC:

Acetyl CoA carboxylase

BMP:

Bis(monoacylglycero)phosphate

C:

Cholesterol

Cer:

Ceramide

Ptd2Gro:

Cardiolipin

FASN:

Fatty acid synthase

FBS:

Fetal bovine serum

GLC:

Gas liquid chromatography

HPTLC:

High performance thin-layer chromatography

lysoPtdCho:

Lysophosphatidylcholine

PtdOH:

Phosphatidic acid

PtdCho:

Phosphatidylcholine

EtnGpl:

Phosphatidylethanolamine

PtdGro:

Phosphatidylglycerol

PtdIns:

Phosphatidylinositol

PtdSer:

Phosphatidylserine

CerPCho:

Sphingomyelin

TAG:

Triacylglycerol

References

  1. Seyfried TN, Flores R, Poff AM, D’Agostino DP, Mukherjee P (2014) Metabolic therapy: a new paradigm for managing malignant brain cancer. Cancer Lett 356:289–300

    Article  PubMed  Google Scholar 

  2. Wen PY, Kesari S (2008) Malignant gliomas in adults. The New England journal of medicine 359:492–507

    Article  CAS  PubMed  Google Scholar 

  3. Portais JC, Voisin P, Merle M, Canioni P (1996) Glucose and glutamine metabolism in C6 glioma cells studied by carbon 13 NMR. Biochimie 78:155–164

    Article  CAS  PubMed  Google Scholar 

  4. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci 104:19345–19350

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Wolf A, Agnihotri S, Guha A (2010) Targeting metabolic remodeling in glioblastoma multiforme. Oncotarget 1:552–562

    Article  PubMed  Google Scholar 

  6. Maher EA, Marin-Valencia I, Bachoo RM, Mashimo T, Raisanen J, Hatanpaa KJ, Jindal A, Jeffrey FM, Choi C, Madden C, Mathews D, Pascual JM, Mickey BE, Malloy CR, DeBerardinis RJ (2012) Metabolism of [U-13 C]glucose in human brain tumors in vivo. NMR Biomed 25:1234–1244

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Qu W, Oya S, Lieberman BP, Ploessl K, Wang L, Wise DR, Divgi CR, Chodosh LA, Thompson CB, Kung HF (2012) Preparation and characterization of L-[5-11C]-glutamine for metabolic imaging of tumors. J Nucl Med Off Publ, Soc Nucl Med 53:98–105

    CAS  Google Scholar 

  8. Gambhir SS (2002) Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2:683–693

    Article  CAS  PubMed  Google Scholar 

  9. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Lunt SY, Vander Heiden MG (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464

    Article  CAS  PubMed  Google Scholar 

  11. Park JB, Lee CS, Jang JH, Ghim J, Kim YJ, You S, Hwang D, Suh PG, Ryu SH (2012) Phospholipase signalling networks in cancer. Nat Rev Cancer 12:782–792

    Article  CAS  PubMed  Google Scholar 

  12. Mills GB, Moolenaar WH (2003) The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 3:582–591

    Article  CAS  PubMed  Google Scholar 

  13. Karmali RA (1986) Eicosanoids and cancer. Prog Clin Biol Res 222:687–697

    CAS  PubMed  Google Scholar 

  14. Wang D, Wang H, Brown J, Daikoku T, Ning W, Shi Q, Richmond A, Strieter R, Dey SK, DuBois RN (2006) CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med 203:941–951

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Rolin J, Maghazachi AA (2011) Effects of lysophospholipids on tumor microenvironment. Cancer Microenviron Off J Int Cancer Microenviron Soc 4:393–403

    Article  CAS  Google Scholar 

  16. Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP, Thompson CB, Rabinowitz JD (2013) Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci 110:8882–8887

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T (2004) Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci 101:591–596

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Clendening JW, Pandyra A, Boutros PC, El Ghamrasni S, Khosravi F, Trentin GA, Martirosyan A, Hakem A, Hakem R, Jurisica I, Penn LZ (2010) Dysregulation of the mevalonate pathway promotes transformation. Proc Natl Acad Sci 107:15051–15056

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Medes G, Thomas A, Weinhouse S (1953) Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res 13:27–29

    CAS  PubMed  Google Scholar 

  20. Ookhtens M, Kannan R, Lyon I, Baker N (1984) Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor. Am J Physiol 247:R146–R153

    CAS  PubMed  Google Scholar 

  21. Yates AJ, Thompson DK, Boesel CP, Albrightson C, Hart RW (1979) Lipid composition of human neural tumors. J Lipid Res 20:428–436

    CAS  PubMed  Google Scholar 

  22. Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS, DeBerardinis RJ (2012) Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 481:385–388

    CAS  Google Scholar 

  23. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, Kelleher JK, Vander Heiden MG, Iliopoulos O, Stephanopoulos G (2012) Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481:380–384

    CAS  Google Scholar 

  24. Scott DA, Richardson AD, Filipp FV, Knutzen CA, Chiang GG, Ronai ZA, Osterman AL, Smith JW (2011) Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effect. J Biol Chem 286:42626–42634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Pizer ES, Chrest FJ, DiGiuseppe JA, Han WF (1998) Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res 58:4611–4615

    CAS  PubMed  Google Scholar 

  26. Pizer ES, Jackisch C, Wood FD, Pasternack GR, Davidson NE, Kuhajda FP (1996) Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res 56:2745–2747

    CAS  PubMed  Google Scholar 

  27. Hochachka PW, Rupert JL, Goldenberg L, Gleave M, Kozlowski P (2002) Going malignant: the hypoxia-cancer connection in the prostate. BioEssay 24:749–757

    Article  CAS  Google Scholar 

  28. Holleran AL, Briscoe DA, Fiskum G, Kelleher JK (1995) Glutamine metabolism in AS-30D hepatoma cells. Evidence for its conversion into lipids via reductive carboxylation. Mol Cell Biochem 152:95–101

    Article  CAS  PubMed  Google Scholar 

  29. Rysman E, Brusselmans K, Scheys K, Timmermans L, Derua R, Munck S, Van Veldhoven PP, Waltregny D, Daniels VW, Machiels J, Vanderhoydonc F, Smans K, Waelkens E, Verhoeven G, Swinnen JV (2010) De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res 70:8117–8126

    Article  CAS  PubMed  Google Scholar 

  30. Pizer ES, Thupari J, Han WF, Pinn ML, Chrest FJ, Frehywot GL, Townsend CA, Kuhajda FP (2000) Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res 60:213–218

    CAS  PubMed  Google Scholar 

  31. Abraham S, Chaikoff IL (1965) Metabolism of Barrett mammary adenocarcinoma: glucose utilization, fatty acid synthesis, and terminal oxidative patterns and glutamine synthesis. Cancer Res 25:647–655

    CAS  PubMed  Google Scholar 

  32. Santos CR, Schulze A (2012) Lipid metabolism in cancer. FEBS J 279:2610–2623

    Article  CAS  PubMed  Google Scholar 

  33. Beaty NB, Lane MD (1983) Kinetics of activation of acetyl-CoA carboxylase by citrate. Relationship to the rate of polymerization of the enzyme. J Biol Chem 258:13043–13050

    CAS  PubMed  Google Scholar 

  34. Bauer DE, Hatzivassiliou G, Zhao F, Andreadis C, Thompson CB (2005) ATP citrate lyase is an important component of cell growth and transformation. Oncogene 24:6314–6322

    Article  CAS  PubMed  Google Scholar 

  35. Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J 8:1248–1259

    CAS  PubMed  Google Scholar 

  36. Bloch K (1965) The biological synthesis of cholesterol. Science 150:19–28

    Article  CAS  PubMed  Google Scholar 

  37. Cairns RA, Harris I, McCracken S, Mak TW (2011) Cancer cell metabolism. Cold Spring Harb Symp Quant Biol 76:299–311

    Article  CAS  PubMed  Google Scholar 

  38. DeBerardinis RJ, Thompson CB (2012) Cellular metabolism and disease: what do metabolic outliers teach us? Cell 148:1132–1144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277:30409–30412

    Article  CAS  PubMed  Google Scholar 

  40. Reitzer LJ, Wice BM, Kennell D (1979) Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 254:2669–2676

    CAS  PubMed  Google Scholar 

  41. Kovacevic Z, Morris HP (1972) The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 32:326–333

    CAS  PubMed  Google Scholar 

  42. Weljie AM, Jirik FR (2011) Hypoxia-induced metabolic shifts in cancer cells: moving beyond the Warburg effect. Int J Biochem Cell Biol 43:981–989

    Article  CAS  PubMed  Google Scholar 

  43. Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7:763–777

    Article  CAS  PubMed  Google Scholar 

  44. Stoll LL, Spector AA (1984) Changes in serum influence the fatty acid composition of established cell lines. In vitro 20:732–738

    Article  CAS  PubMed  Google Scholar 

  45. Rothblat GH, Arbogast LY, Ouellette L, Howard BV (1976) Preparation of delipidized serum protein for use in cell culture systems. In vitro 12:554–557

    Article  CAS  PubMed  Google Scholar 

  46. Huysentruyt LC, Mukherjee P, Banerjee D, Shelton LM, Seyfried TN (2008) Metastatic cancer cells with macrophage properties: evidence from a new murine tumor model. Int J Cancer 123:73–84

    Article  CAS  PubMed  Google Scholar 

  47. Shelton LM, Mukherjee P, Huysentruyt LC, Urits I, Rosenberg JA, Seyfried TN (2010) A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion. J Neurooncol 99:165–176

    Article  CAS  PubMed  Google Scholar 

  48. Huysentruyt LC, Akgoc Z, Seyfried TN (2011) Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme? ASN neuro 3:AN20110011

    Google Scholar 

  49. Seyfried TN, Glaser GH, Yu RK (1978) Cerebral, cerebellar, and brain stem gangliosides in mice susceptible to audiogenic seizures. J Neurochem 31:21–27

    Article  CAS  PubMed  Google Scholar 

  50. Baek RC, Kasperzyk JL, Platt FM, Seyfried TN (2004) N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal sandhoff disease mice. J Neurochem 90(Suppl 1):89

    Google Scholar 

  51. Macala LJ, Yu RK, Ando S (1983) Analysis of brain lipids by high performance thin-layer chromatography and densitometry. J Lipid Res 24:1243–1250

    CAS  PubMed  Google Scholar 

  52. Kasperzyk JL, d’Azzo A, Platt FM, Alroy J, Seyfried TN (2005) Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice. J Lipid Res 46:744–751

    Article  CAS  PubMed  Google Scholar 

  53. Kasperzyk JL, El-Abbadi MM, Hauser EC, D’Azzo A, Platt FM, Seyfried TN (2004) N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis. J Neurochem 89:645–653

    Article  CAS  PubMed  Google Scholar 

  54. Yuneva M (2008) Finding an “Achilles’ heel” of cancer: the role of glucose and glutamine metabolism in the survival of transformed cells. Cell Cycle 7:2083–2089

    Article  CAS  PubMed  Google Scholar 

  55. Teicher BA, Linehan WM, Helman LJ (2012) Targeting cancer metabolism. Clin Cancer Res Off J Am Assoc Cancer Res 18:5537–5545

    Article  CAS  Google Scholar 

  56. Vander Heiden MG (2011) Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 10:671–684

    Article  CAS  PubMed  Google Scholar 

  57. Dang CV, Hamaker M, Sun P, Le A, Gao P (2011) Therapeutic targeting of cancer cell metabolism. J Mol Med 89:205–212

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. 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 53:29–48

    Article  CAS  PubMed  Google Scholar 

  59. Piva TJ, McEvoy-Bowe E (1998) Oxidation of glutamine in HeLa cells: role and control of truncated TCA cycles in tumour mitochondria. J Cell Biochem 68:213–225

    Article  CAS  PubMed  Google Scholar 

  60. Souba WW (1993) Glutamine and cancer. Ann Surg 218:715–728

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Moreadith RW, Lehninger AL (1984) The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P) + -dependent malic enzyme. J Biol Chem 259:6215–6221

    CAS  PubMed  Google Scholar 

  62. Lu W, Pelicano H, Huang P (2010) Cancer metabolism: is glutamine sweeter than glucose? Cancer Cell 18:199–200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Meng M, Chen S, Lao T, Liang D, Sang N (2010) Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells. Cell Cycle 9:3921–3932

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Zhang F, Du G (2012) Dysregulated lipid metabolism in cancer. World J Biol Chem 3:167–174

    Article  PubMed Central  PubMed  Google Scholar 

  65. Vazquez-Martin A, Colomer R, Brunet J, Lupu R, Menendez JA (2008) Overexpression of fatty acid synthase gene activates HER1/HER2 tyrosine kinase receptors in human breast epithelial cells. Cell Prolif 41:59–85

    Article  CAS  PubMed  Google Scholar 

  66. Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA, Thompson CB (2005) ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8:311–321

    Article  CAS  PubMed  Google Scholar 

  67. Ecsedy JA, Holthaus KA, Yohe HC, Seyfried TN (1999) Expression of mouse sialic acid on gangliosides of a human glioma grown as a xenograft in SCID mice. J Neurochem 73:254–259

    Article  CAS  PubMed  Google Scholar 

  68. Louie SM, Roberts LS, Mulvihill MM, Luo K, Nomura DK (2013) Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids. Biochim Biophys Acta 1831:1566–1572

    Article  CAS  PubMed  Google Scholar 

  69. Kuemmerle NB, Rysman E, Lombardo PS, Flanagan AJ, Lipe BC, Wells WA, Pettus JR, Froehlich HM, Memoli VA, Morganelli PM, Swinnen JV, Timmerman LA, Chaychi L, Fricano CJ, Eisenberg BL, Coleman WB, Kinlaw WB (2011) Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol Cancer Ther 10:427–436

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Filipp FV, Scott DA, Ronai ZA, Osterman AL, Smith JW (2012) Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cells. Pigment Cell Melanoma Res 25:375–383

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB (2011) Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci 108:19611–19616

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. van den Heuvel AP, Jing J, Wooster RF, Bachman KE (2012) Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth. Cancer Biol Ther 13:1185–1194

    Article  PubMed Central  PubMed  Google Scholar 

  73. Fan J, Kamphorst JJ, Mathew R, Chung MK, White E, Shlomi T, Rabinowitz JD (2013) Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Mol Syst Biol 9:712

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. McGuirk S, Gravel SP, Deblois G, Papadopoli DJ, Faubert B, Wegner A, Hiller K, Avizonis D, Akavia UD, Jones RG, Giguere V, St-Pierre J (2013) PGC-1alpha supports glutamine metabolism in breast cancer. Cancer Metab 1:22

    Article  PubMed Central  PubMed  Google Scholar 

  75. Semenza GL (2007) HIF-1 mediates the Warburg effect in clear cell renal carcinoma. J Bioenerg Biomembr 39:231–234

    Article  CAS  PubMed  Google Scholar 

  76. Semenza GL, Artemov D, Bedi A, Bhujwalla Z, Chiles K, Feldser D, Laughner E, Ravi R, Simons J, Taghavi P, Zhong H (2001) The metabolism of tumours’: 70 years later. Novartis Found Symp 240:251–260 (discussion 260–254 )

    Article  CAS  PubMed  Google Scholar 

  77. Dang CV, Semenza GL (1999) Oncogenic alterations of metabolism. Trends Biochem Sci 24:68–72

    Article  CAS  PubMed  Google Scholar 

  78. Mylonis I, Sembongi H, Befani C, Liakos P, Siniossoglou S, Simos G (2012) Hypoxia causes triglyceride accumulation by HIF-1-mediated stimulation of lipin 1 expression. J Cell Sci 125:3485–3493

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Brose SA, Marquardt AL, Golovko MY (2014) Fatty acid biosynthesis from glutamate and glutamine is specifically induced in neuronal cells under hypoxia. J Neurochem 129:400–412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Bensaad K, Favaro E, Lewis CA, Peck B, Lord S, Collins JM, Pinnick KE, Wigfield S, Buffa FM, Li JL, Zhang Q, Wakelam MJ, Karpe F, Schulze A, Harris AL (2014) Fatty acid uptake and lipid storage induced by HIF-1alpha contribute to cell growth and survival after hypoxia-reoxygenation. Cell reports 9:349–365

    Article  CAS  PubMed  Google Scholar 

  81. Liu K, Czaja MJ (2013) Regulation of lipid stores and metabolism by lipophagy. Cell Death Differ 20:3–11

    Article  PubMed Central  PubMed  Google Scholar 

  82. Singh R, Cuervo AM (2012) Lipophagy: connecting autophagy and lipid metabolism. Int J Cell Biol 2012:282041

    Article  PubMed Central  PubMed  Google Scholar 

  83. Tugnoli V, Tosi MR, Tinti A, Trinchero A, Bottura G, Fini G (2001) Characterization of lipids from human brain tissues by multinuclear magnetic resonance spectroscopy. Biopolymers 62:297–306

    Article  CAS  PubMed  Google Scholar 

  84. Opstad KS, Ladroue C, Bell BA, Griffiths JR, Howe FA (2007) Linear discriminant analysis of brain tumour (1)H MR spectra: a comparison of classification using whole spectra versus metabolite quantification. NMR Biomed 20:763–770

    Article  CAS  PubMed  Google Scholar 

  85. Nguyen AD, McDonald JG, Bruick RK, DeBose-Boyd RA (2007) Hypoxia stimulates degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase through accumulation of lanosterol and hypoxia-inducible factor-mediated induction of insigs. J Biol Chem 282:27436–27446

    Article  CAS  PubMed  Google Scholar 

  86. Summons RE, Bradley AS, Jahnke LL, Waldbauer JR (2006) Steroids, triterpenoids and molecular oxygen. Philos Trans R Soc Lond B Biol Sci 361:951–968

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Yin J, Hashimoto A, Izawa M, Miyazaki K, Chen GY, Takematsu H, Kozutsumi Y, Suzuki A, Furuhata K, Cheng FL, Lin CH, Sato C, Kitajima K, Kannagi R (2006) Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells. Cancer Res 66:2937–2945

    Article  CAS  PubMed  Google Scholar 

  88. Bouterfa HL, Sattelmeyer V, Czub S, Vordermark D, Roosen K, Tonn JC (2000) Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cells. Anticancer Res 20:2761–2771

    CAS  PubMed  Google Scholar 

  89. Bifulco M (2005) Role of the isoprenoid pathway in ras transforming activity, cytoskeleton organization, cell proliferation and apoptosis. Life Sci 77:1740–1749

    Article  CAS  PubMed  Google Scholar 

  90. Zhong WB, Liang YC, Wang CY, Chang TC, Lee WS (2005) Lovastatin suppresses invasiveness of anaplastic thyroid cancer cells by inhibiting Rho geranylgeranylation and RhoA/ROCK signaling. Endocr Relat Cancer 12:615–629

    Article  CAS  PubMed  Google Scholar 

  91. Thibault A, Samid D, Tompkins AC, Figg WD, Cooper MR, Hohl RJ, Trepel J, Liang B, Patronas N, Venzon DJ, Reed E, Myers CE (1996) Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Off J Am Assoc Cancer Res 2:483–491

    CAS  Google Scholar 

  92. Larner J, Jane J, Laws E, Packer R, Myers C, Shaffrey M (1998) A phase I-II trial of lovastatin for anaplastic astrocytoma and glioblastoma multiforme. Am J Clin Oncol 21:579–583

    Article  CAS  PubMed  Google Scholar 

  93. Kim WS, Kim MM, Choi HJ, Yoon SS, Lee MH, Park K, Park CH, Kang WK (2001) Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Invest New Drugs 19:81–83

    Article  CAS  PubMed  Google Scholar 

  94. Lersch C, Schmelz R, Erdmann J, Hollweck R, Schulte-Frohlinde E, Eckel F, Nader M, Schusdziarra V (2004) Treatment of HCC with pravastatin, octreotide, or gemcitabine—a critical evaluation. Hepatogastroenterology 51:1099–1103

    CAS  PubMed  Google Scholar 

  95. Baek RC, Kasperzyk JL, Platt FM, Seyfried TN (2008) N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal sandhoff disease mice. Neurochem Int 52:1125–1133

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biology Department, Boston College, Chestnut Hill, Boston, MA, 02467, USA

    Nathan L. Ta & Thomas N. Seyfried

Authors
  1. Nathan L. Ta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas N. Seyfried
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas N. Seyfried.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ta, N.L., Seyfried, T.N. Influence of Serum and Hypoxia on Incorporation of [14C]-d-Glucose or [14C]-l-Glutamine into Lipids and Lactate in Murine Glioblastoma Cells. Lipids 50, 1167–1184 (2015). https://doi.org/10.1007/s11745-015-4075-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-015-4075-z

Keywords

Search

Navigation