Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth

Cancer Research

Volumn 67, Issue 14, 2007, Pages 6745-6752

  Buzzai, Monica ^a   Jones, Russell G ^a   Amaravadi, Ravi K ^a,b   Lum, Julian J ^a   DeBerardinis, Ralph J ^a,c   Zhao, Fangping ^a   Viollet, Benoit ^d,e   Thompson, Craig B ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^d INSTITUT COCHIN   (France)

^e INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; FATTY ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; METFORMIN; PROTEIN P53;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CELL CULTURE; CANCER GROWTH; CANCER INHIBITION; CANCER PREVENTION; CANCER SUSCEPTIBILITY; CELL GROWTH; COLON CANCER; CONTROLLED STUDY; DRUG EFFECT; ELECTRON TRANSPORT; FATTY ACID OXIDATION; FEMALE; FIBROBLAST CULTURE; GLYCOLYSIS; HUMAN; HUMAN CELL; IN VITRO STUDY; MITOCHONDRIAL MEMBRANE; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEIN PHOSPHORYLATION; TUMOR CELL; XENOGRAFT;

ANIMALS; APOPTOSIS; CELL LINE, TUMOR; CELL PROLIFERATION; FIBROBLASTS; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; MICE; MICE, TRANSGENIC; MITOCHONDRIA; MULTIENZYME COMPLEXES; NEOPLASM TRANSPLANTATION; NEOPLASMS; PROTEIN-SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 34547114031     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-06-4447     Document Type: Article

References (35)

1. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005;1:15-25.
2. Witters LA. The blooming of the French lilac. J Clin Invest 2001;108:1105-7.
3. Hundal HS, Ramlal T, Reyes R, Leiter LA, Klip A. Cellular mechanism of metformin action involves glucose transporter translocation from an intracellular pool to the plasma membrane in L6 muscle cells. Endocrinology 1992;131:1165-73.
4. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 1995;333:550-4.
5. Fryer LG, Parbu-Patel A, Carling D. The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 2002;277:25226-32.
6. Hawley SA, Gadalla AE, Olsen GS, Hardie DG. The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 2002;51:2420-5.
7. Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-74.
8. Koo SH, Flechner L, Qi L, et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005;437:1109-11.
9. Screaton RA, Conkright MD, Katoh Y, et al. The CREB coactivator TORC2 functions as a calcium-and cAMP-sensitive coincidence detector. Cell 2004;119:61-74.
10. Shaw RJ, Lamia KA, Vasquez D, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005;310:1642-6.
11. Carling D. The AMP-activated protein kinase cascade - a unifying system for energy control. Trends Biochem Sci 2004;29:18-24.
12. Jones RG, Plas DR, Kubek S, et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005;18:283-93.
13. Bensaad K, Tsuruta A, Selak MA, et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107-20.
14. Matoba S, Kang JG, Patino WD, et al. p53 regulates mitochondrial respiration. Science 2006;312:1650-3.
15. Warburg O, Posener K, Negelein E. Uber den stoffwechsel der tumoren. Biochem Z 1924;152:319-44.
16. Crighton D, Wilkinson S, O'Prey J, et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 2006;126:121-34.
17. Lum JJ, Bauer DE, Kong M, et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 2005;120:237-48.
18. Feng Z, Zhang H, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A 2005;102:8204-9.
19. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330:1304-5.
20. Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29:254-8.
21. Laderoute KR, Amin K, Calaoagan JM, et al. 5′-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol 2006;26:5336-47.
22. Deberardinis RJ, Lum JJ, Thompson CB. PI3K-dependent modulation of CPT1A expression regulates lipid metabolism during hematopoietic cell growth. J Biol Chem 2006;281:37372-80.
23. Schumacker PT, Chandel N, Agusti AG. Oxygen conformance of cellular respiration in hepatocytes. Am J Physiol 1993;265:395-402.
24. Buzzai M, Bauer DE, Jones RG, et al. The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid β-oxidation. Oncogene 2005;24:4165-73.
25. Lilly K, Chung C, Kerner J, VanRenterghem R, Bieber LL. Effect of etomoxiryl-CoA on different carnitine acyltransferases. Biochem Pharmacol 1992;43:353-61.
26. Lam E. Controlled cell death, plant survival and development. Nat Rev Mol Cell Biol 2004;5:305-15.
27. Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000;19:5720-8.
28. Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B. Autophagy genes are essential for Dauer development and life-span extension in C. elegans. Science 2003;301:1387-91.
29. Mizushima N. Methods for monitoring autophagy. Int J Biochem Cell Biol 2004;36:2491-502.
30. James F, Brouquisse R, Suire C, Pradet A, Raymond P. Purification and biochemical characterization of a vacuolar serine endopeptidase induced by glucose starvation in maize roots. Biochem J 1996;320:283-92.
31. El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 2000;275:223-8.
32. Schafer G. Biguanides. A review of history, pharmacodynamics and therapy. Diabetes Metab 1983;9:148-63.
33. Degenhardt K, Mathew R, Beaudoin B, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006;10:51-64.
34. Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 2001;294:1942-5.
35. Amaravadi RK, Yu D, Lum JJ, et al. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 2007;117:326-36.