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References (57)
-
LG Boros, DJ Brackett, GG Harrigan (2003)
Metabolic biomarker and kinase drug target discovery in cancer using stable isotope-based dynamic metabolic profiling (SIDMAP)Current Cancer Drug Targets, 3
-
D Li, SC Yeung, MM Hassan, M Konopleva, JL Abbruzzese (2009)
Antidiabetic therapies affect risk of pancreatic cancerGastroenterology, 137
-
JH Cheong, ES Park, J Liang, JB Dennison, D Tsavachidou, C Nguyen-Charles (2011)
Dual inhibition of tumor energy pathway by 2-deoxyglucose and metformin is effective against a broad spectrum of preclinical cancer modelsMolecular Cancer Therapeutics, 10
-
E Fitzgerald, S Mathieu, A Ball (2009)
Metformin associated lactic acidosisBMJ, 339
-
G Libby, LA Donnelly, PT Donnan, DR Alessi, AD Morris, JM Evans (2009)
New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. [Research Support, Non-U.S. Gov’t]Diabetes Care, 32
-
S Bo, G Ciccone, R Rosato, P Villois, G Appendino, E Ghigo (2011)
Cancer mortality reduction and metformin: A retrospective cohort study in type 2 diabetic patientsDiabetes Obesity and Metabolism, 14
-
EL Deer, J Gonzalez-Hernandez, JD Coursen, JE Shea, J Ngatia, CL Scaife (2010)
Phenotype and genotype of pancreatic cancer cell linesPancreas, 39
-
(Ben Sahra, I., Tanti, J. F., & Bost, F. (2010b). The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells. Autophagy, 6(5). doi:10.1158/0008-5472.CAN-09-2782.)
Ben Sahra, I., Tanti, J. F., & Bost, F. (2010b). The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells. Autophagy, 6(5). doi:10.1158/0008-5472.CAN-09-2782.Ben Sahra, I., Tanti, J. F., & Bost, F. (2010b). The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells. Autophagy, 6(5). doi:10.1158/0008-5472.CAN-09-2782., Ben Sahra, I., Tanti, J. F., & Bost, F. (2010b). The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells. Autophagy, 6(5). doi:10.1158/0008-5472.CAN-09-2782.
-
JM Evans, LA Donelly, AM Emslie-Smith, DR Alessi, AD Morris (2005)
Metformin and reduced risk of cancer in diabetic patientsBritish Medical Journal, 330
-
JA Menendez, C Oliveras-Ferraros, S Cufi, B Corominas-Faja, J Joven, B Martin-Castillo (2012)
Metformin is synthetically lethal with glucose withdrawal in cancer cellsCell Cycle, 11
-
K Kisfalvi, G Eibl, J Sinnett-Smith, E Rozengurt (2009)
Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growthCancer Research, 69
-
JA Menendez, R Lupu (2007)
Fatty acid synthase and the lipogenic phenotype in cancer pathogenesisNature Reviews Cancer, 7
-
M Monami, C Colombi, D Balzi, I Dicembrini, S Giannini, C Melani (2011)
Metformin and cancer occurrence in insulin-treated type 2 diabetic patientsDiabetes Care, 34
-
I Ben Sahra, C Regazzetti, G Robert, K Laurent, Y Marchand-Brustel, P Auberger (2011)
Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1Cancer Research, 71
-
A Bulotta, R Perfetti, H Hui, LG Boros (2003)
GLP-1 stimulates glucose-derived de novo fatty acid synthesis and chain elongation during cell differentiation and insulin releaseJournal of Lipid Research, 44
-
VC Sandulache, TJ Ow, CR Pickering, MJ Frederick, G Zhou, I Fokt (2011)
Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cellsCancer, 117
-
DJ Preiss, N Sattar (2009)
Metformin and lactic acidosis. Metformin: Framed again?British Medical Journal, 23
-
M Pollak (2012)
Metformin and pancreatic cancer: A clue requiring investigationClinical Cancer Research, 18
-
WN Lee (1996)
Stable isotopes and mass isotopomer study of fatty acid and cholesterol synthesis a review of the MIDA approachAdvances in Experimental Medicine and Biology, 399
-
CM Metallo, JL Walther, G Stephanopoulos (2009)
Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cellsJournal of Biotechnology, 144
-
MM Mihaylova, RJ Shaw (2011)
The AMPK signalling pathway coordinates cell growth, autophagy and metabolismNature Cell Biology, 13
-
I Ben Sahra, K Laurent, S Giuliano, F Larbret, G Ponzio, P Gounon (2010)
Targeting cancer cell metabolism: The combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cellsCancer Research, 70
-
DO Espinoza, LG Boros, S Crunkhorn, H Gami, ME Patti (2010)
Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubesFederation of American Societies for Experimental Biology Journal, 24
-
MM Gonzalez-Barroso, A Anedda, E Gallardo-Vara, M Redondo-Horcajo, L Rodriguez-Sanchez, E Rial (2012)
Fatty acids revert the inhibition of respiration caused by the antidiabetic drug metformin to facilitate their mitochondrial beta-oxidationBiochimica et Biophysica Acta
-
JA Dykens, J Jamieson, L Marroquin, S Nadanaciva, PA Billis, Y Will (2008)
Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitroToxicology and Applied Pharmacology, 233
-
E Kim, N-C Liu, I-C Yu, H-Y Lin, Y-F Lee, JD Sparks (2011)
Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivityDiabetes, 60
-
R Ruiter, LE Visser, MPP Herk-Sukel, J-WW Coebergh, HR Haal, PH Geelhoed-Duijvestijn (2012)
Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivativesDiabetes Care, 35
-
A Kalender, A Selvaraj, SY Kim, P Gulati, S Brule, B Viollet (2010)
Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent mannerCell Metabolism, 11
-
E Lopez-Crapez, C Chypre, J Saavedra, J Marchand, J Grenier (1997)
Rapid and large-scale method to detect K-ras gene mutations in tumor samplesClinical Chemistry, 43
-
JS Goodwin, KR Drake, CL Remmert, AK Kenworthy (2005)
Ras diffusion is sensitive to plasma membrane viscosityBiophysical Journal, 89
-
Y Sancak, TR Peterson, YD Shaul, RA Lindquist, CC Thoreen, L Bar-Peled (2008)
The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1Science, 320
-
JP Fulgencio, C Kohl, J Girard, JP Pegorier (2001)
Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytesBiochemical Pharmacology, 62
-
DJ Creek, A Chokkathukalam, A Jankevics, KE Burgess, R Breitling, MP Barrett (2012)
Stable isotope-assisted metabolomics for network-wide metabolic pathway elucidationAnalytical Chemistry, 84
-
D Whitaker-Menezes, UE Martinez-Outschoorn, N Flomenberg, RC Birbe, AK Witkiewicz, A Howell (2011)
Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: Visualizing the therapeutic effects of metformin in tumor tissueCell Cycle, 10
-
N Wiernsperger, JR Rapin (1995)
Metformin-insulin interactions: From organ to cellDiabetes/Metabolism Reviews, 11
-
C Algire, L Amrein, M Zakikhani, L Panasci, M Pollak (2010)
Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthaseEndocrine Related Cancer, 17
-
GG Harrigan, J Colca, S Szalma, LG Boros (2006)
PNU-91325 increases fatty acid synthesis from glucose and mitochondrial long chain fatty acid degradation: a comparative tracer-based metabolomics study with rosiglitazone and pioglitazone in HepG2 cellsMetabolomics, 2
-
SL Bowker, SR Majumdar, P Veugellers, JA Johnson (2006)
Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulinDiabetes Care, 29
-
Y Sancak, L Bar-Peled, R Zoncu, AL Markhard, S Nada, DM Sabatini (2010)
Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acidsCell, 141
-
D Silva, P Ausina, EM Alencar, WS Coelho, P Zancan (2012)
Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic miceIUBMB Life
-
B Viollet, B Guigas, N Sans Garcia, J Leclerc, M Foretz, F Adreelli (2012)
Cellular and molecular mechanisms of metformin: An overviewClinical Science, 122
-
C Algire, M Zakikhani, MJ Blouin, JH Shuai, M Pollak (2008)
Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growthEndocrine Related Cancer, 15
-
WN Lee, EA Bergner, ZK Guo (1992)
Mass isotopomer pattern and precursor-product relationshipBiological Mass Spectrometry, 21
-
W-NP Lee, LG Boros, J Puigjaner, S Bassilian, S Lim, M Cascante (1998)
Mass isotopomer study of the non-oxidative pathways of the pentose cycle with [1,2–13C2]glucoseAmerican Journal of Physiology, 274
-
S Barco, A Vazquez-Martin, S Cufi, C Oliveras-Ferraros, J Bosch-Barrera, J Joven (2011)
Metformin: Multi-faceted protection against cancerOncotarget, 2
-
N Sadeghi, JL Abbruzzese, SC Yeung, M Hassan, D Li (2012)
Metformin use is associated with better survival of diabetic patients with pancreatic cancerClinical Cancer Research, 18
-
SJ Wakil, LA Abu-Elheiga (2009)
Fatty acid metabolism: Target for metabolic syndromeJournal of Lipid Research, 50
-
EJ Meuillet, N Wiernsperger, B Mania-Farnell, P Hubert, G Cremel (1999)
Metformin modulates insulin receptor signaling in normal and cholesterol-treated human hepatoma cells (HepG2). [Research Support, Non-U.S. Gov’t]European Journal of Pharmacology, 377
-
P Vizan, LG Boros, A Figueras, G Capella, R Mangues, S Bassilian (2005)
K-ras codon-specific mutations produce distinctive metabolic phenotypes in NIH3T3 mice [corrected] fibroblastsCancer Research, 65
-
K Hiller, A Wegner, D Weindl, T Cordes, CM Metallo, JK Kelleher, G Stephanopoulos (2013)
NTFD—a stand-alone application for the non-targeted detection of stable isotope-labeled compounds in GC/MS dataBioinformatics, 29
-
B Guigas, L Bertrand, N Taleux, M Foretz, N Wiernsperger, D Vertommen (2006)
5-aminoimidazole-4-carboxamide-1-B-d-ribofuranoside and metformin inhibit glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocationDiabetes, 55
-
EJ Meuillet, V Leray, P Hubert, C Leray, G Cremel (1999)
Incorporation of exogenous lipids modulates insulin signaling in the hepatoma cell line, HepG2Biochimica et Biophysica Acta, 1454
-
DM Harris, L Li, M Chen, FT Lagunero, VLW Go, LG Boros (2012)
Diverse mechanisms of growth inhibition by luteolin, resveratrol, and quercetin in MIA PaCa-2 cells: A comparative glucose tracer study with fatty acid synthase inhibitor C75Metabolomics, 8
-
JL Little, SJ Kridel (2008)
Fatty acid synthase activity in tumor cellsSubCellular Biochemistry, 49
-
K Walter, SM Hong, S Nyhan, M Canto, N Fedarko, A Klein (2009)
Serum fatty acid synthase as a marker of pancreatic neoplasiaCancer Epidemiol Biomarkers Prev, 18
-
K Bhalla, BJ Hwang, RE Dewi, W Twaddel, OG Goloubeva, KK Wong (2012)
Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesisCancer Prevention Research (Philadelphia), 5
-
R Flavin, S Peluso, PL Nguyen, M Loda (2010)
Fatty acid synthase as a potential therapeutic target in cancerFuture Oncology, 6
- Publisher
- Springer Journals
- Copyright
- Copyright © 2013 by The Author(s)
- Subject
- Life Sciences; Biochemistry, general; Molecular Medicine; Cell Biology; Developmental Biology; Biomedicine, general
- ISSN
- 1573-3882
- eISSN
- 1573-3890
- DOI
- 10.1007/s11306-013-0555-4
- Publisher site
- See Article on Publisher Site
Abstract
Metformin, a generic glucose lowering drug, inhibits cancer growth expressly in models that employ high fat/cholesterol intake and/or low glucose availability. Here we use a targeted tracer fate association study (TTFAS) to investigate how cholesterol and metformin administration regulates glucose-derived intermediary metabolism and macromolecule synthesis in pancreatic cancer cells. Wild type K-ras BxPC-3 and HOM: GGT(Gly) → TGT(Cys) K12 transformed MIA PaCa-2 adenocarcinoma cells were cultured in the presence of [1,2-13C2]-d-glucose as the single tracer for 24 h and treated with either 100 μM metformin (MET), 1 mM cholesteryl hemisuccinate (CHS), or the dose matching combination of MET and CHS (CHS–MET). Wild type K-ras cells used 11.43 % (SD = ±0.32) of new acetyl-CoA for palmitate synthesis that was derived from glucose, while K-ras mutated MIA PaCa-2 cells shuttled less than half as much, 5.47 % [SD = ±0.28 (P < 0.01)] of this precursor towards FAS. Cholesterol treatment almost doubled glucose-derived acetyl-CoA enrichment to 9.54 % (SD = ±0.24) and elevated the fraction of new palmitate synthesis by over 2.5-fold in MIA PaCa-2 cells; whereby 100 μM MET treatment resulted in a 28 % inhibitory effect on FAS. Therefore, acetyl-CoA shuttling towards its carboxylase, from thiolase, produces contextual synthetic inhibition by metformin of new palmitate production. Thereby, metformin, mutated K-ras and high cholesterol each contributes to limit new fatty acid and potentially cell membrane synthesis, demonstrating a previously unknown mechanism for inhibiting cancer growth during the metabolic syndrome.
Journal
Metabolomics – Springer Journals
Published: Jun 26, 2013