MDM2 inhibitor, Nutlin 3a, induces p53 dependent autophagy in acute leukemia by AMP kinase activation

PLoS ONE

Volumn 10, Issue 10, 2015, Pages

  Borthakur, Gautam ^a   Duvvuri, Seshagiri ^a   Ruvolo, Vivian ^a   Tripathi, Durga Nand ^b   Piya, Sujan ^a   Burks, Jared ^a   Jacamo, Rodrigo ^a   Kojima, Kensuke ^a   Ruvolo, Peter ^a   Fueyo Margareto, Juan ^a   Konopleva, Marina ^a   Andreeff, Michael ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE KINASE; BAFILOMYCIN; BECLIN 1; NUTLIN 3; PROTEIN MDM2; PROTEIN P53; IMIDAZOLE DERIVATIVE; PIPERAZINE DERIVATIVE;

ACUTE LEUKEMIA; APOPTOSIS; ARTICLE; AUTOPHAGY; CELL CYCLE ARREST; CELL SURVIVAL; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DISEASE SEVERITY; ENVIRONMENTAL STRESS; FLOW CYTOMETRY; FLUORESCENCE MICROSCOPY; HUMAN; HUMAN CELL; PLASMID; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSMISSION ELECTRON MICROSCOPY; UPREGULATION; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; ENZYME ACTIVATION; GENETICS; LENTIVIRINAE; LEUKEMIA; METABOLISM; TUMOR CELL LINE; WESTERN BLOTTING;

ADENYLATE KINASE; AUTOPHAGY; BLOTTING, WESTERN; CELL LINE, TUMOR; ENZYME ACTIVATION; FLOW CYTOMETRY; HUMANS; IMIDAZOLES; LENTIVIRUS; LEUKEMIA; MICROSCOPY, CONFOCAL; MICROSCOPY, ELECTRON, TRANSMISSION; PIPERAZINES; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84947968556     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0139254     Document Type: Article

References (33)

1. Lozano G, Montes de Oca Luna R. MDM2 function. Biochim Biophys Acta. 1998; 1377(2):M55-9. Epub 1998/06/02. PMID: 9606977.
2. Montes de Oca Luna R, Wagner DS, Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature. 1995; 378(6553):203-6. Epub 1995/11/09. doi: 10.1038/378203a0 PMID: 7477326.
3. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004; 303(5659):844-8. Epub 2004/01/06. doi: 10.1126/science.1092472 PMID: 14704432.
4. Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, McQueen T, et al. MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood. 2005; 106 (9):3150-9. Epub 2005/07/15. doi: 10.1182/blood-2005-02-0553 PMID: 16014563; PubMed Central PMCID: PMC1895324.
5. Andreeff M, Kojima K, Padmanabhan S, Strair R, Kirschbaum M, Maslak P, et al. A Multi-Center, Open-Label, Phase I Study of Single Agent RG7112, A First In Class p53-MDM2 Antagonist, In Patients with Relapsed/Refractory Acute Myeloid and Lymphoid Leukemias (AML/ALL) and Refractory Chronic Lymphocytic Leukemia/Small Cell Lymphocytic Lymphomas (CLL/SCLL). ASH Annual Meeting Abstracts. 2010; 116(21):657-.
6. Altman BJ, Rathmell JC. Metabolic stress in autophagy and cell death pathways. Cold Spring Harb Perspect Biol. 2012; 4(9):a008763. Epub 2012/09/07. doi: 10.1101/cshperspect.a008763 PMID: 22952396; PubMed Central PMCID: PMC3428762.
7. Abeliovich H. Mitophagy: the life-or-death dichotomy includes yeast. Autophagy. 2007; 3(3):275-7. Epub 2007/03/03. PMID: 17329958.
8. Wu WK, Coffelt SB, Cho CH, Wang XJ, Lee CW, Chan FK, et al. The autophagic paradox in cancer therapy. Oncogene. 2012; 31(8):939-53. Epub 2011/07/19. doi: 10.1038/onc.2011.295 PMID: 21765470.
9. Levine B, Abrams J. p53: The Janus of autophagy? Nature cell biology. 2008; 10(6):637-9. Epub 2008/06/04. doi: 10.1038/ncb0608-637 PMID: 18521069; PubMed Central PMCID: PMC2739720.
10. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, et al. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest. 2007; 117(2):326-36. Epub 2007/01/20. doi: 10.1172/JCI28833 PMID: 17235397; PubMed Central PMCID: PMC1765515.
11. Tasdemir E, Maiuri MC, Galluzzi L, Vitale I, Djavaheri-Mergny M, D'Amelio M, et al. Regulation of autophagy by cytoplasmic p53. Nature cell biology. 2008; 10(6):676-87. Epub 2008/05/06. doi: 10.1038/ncb1730 PMID: 18454141; PubMed Central PMCID: PMC2676564.
12. Maiuri MC, Galluzzi L, Morselli E, Kepp O, Malik SA, Kroemer G. Autophagy regulation by p53. Current opinion in cell biology. 2010; 22(2):181-5. Epub 2010/01/02. doi: 10.1016/j.ceb.2009.12.001 PMID: 20044243.
13. Lee IH, Kawai Y, Fergusson MM, Rovira II, Bishop AJ, Motoyama N, et al. Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science. 2012; 336(6078):225-8. Epub 2012/04/14. doi: 10.1126/science.1218395 PMID: 22499945.
14. Gao W, Shen Z, Shang L, Wang X. Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death. Cell Death Differ. 2011; 18(10):1598-607. doi: 10.1038/cdd.2011.33 PMID: 21475306; PubMed Central PMCID: PMC3172118.
15. Yang GS, Minden MD, McCulloch EA. Influence of schedule on regulated sensitivity of AML blasts to cytosine arabinoside. Leukemia. 1993; 7(7):1012-9. PMID: 7686602.
16. Kojima K, Shimanuki M, Shikami M, Samudio IJ, Ruvolo V, Corn P, et al. The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML. Leukemia. 2008; 22(9):1728-36. doi: 10.1038/leu.2008.158 PMID: 18548093.
17. Laderoute KR, Amin K, Calaoagan JM, Knapp M, Le T, Orduna J, et al. 5′-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Molecular and cellular biology. 2006; 26(14):5336-47. doi: 10.1128/MCB.00166-06 PMID: 16809770; PubMed Central PMCID: PMC1592699.
18. Vazquez CL, Colombo MI. Assays to assess autophagy induction and fusion of autophagic vacuoles with a degradative compartment, using monodansylcadaverine (MDC) and DQ-BSA. Methods in enzymology. 2009; 452:85-95. Epub 2009/02/10. doi: 10.1016/S0076-6879(08)03606-9 PMID: 19200877.
19. Nyfeler B, Bergman P, Wilson CJ, Murphy LO. Quantitative visualization of autophagy induction by mTOR inhibitors. Methods in molecular biology. 2012; 821:239-50. Epub 2011/11/30. doi: 10.1007/978-1-61779-430-8-14 PMID: 22125069.
20. Kojima K, Kornblau SM, Ruvolo V, Dilip A, Duvvuri S, Davis RE, et al. Prognostic impact and targeting of CRM1 in acute myeloid leukemia. Blood. 2013; 121(20):4166-74. doi: 10.1182/blood-2012-08-447581 PMID: 23564911; PubMed Central PMCID: PMC3656451.
21. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008; 4(2):151-75. Epub 2008/01/12. PMID: 18188003; PubMed Central PMCID: PMC2654259.
22. Davies SP, Hawley SA, Woods A, Carling D, Haystead TA, Hardie DG. Purification of the AMP-activated protein kinase on ATP-gamma-sepharose and analysis of its subunit structure. Eur J Biochem. 1994; 223(2):351-7. Epub 1994/07/15. PMID: 8055903.
23. Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, et al. Mammalian AMP-activated protein kinase subfamily. J Biol Chem. 1996; 271(2):611-4. PMID: 8557660.
24. Gao G, Fernandez CS, Stapleton D, Auster AS, Widmer J, Dyck JR, et al. Non-catalytic beta- and gamma-subunit isoforms of the 5′-AMP-activated protein kinase. J Biol Chem. 1996; 271(15):8675-81. PMID: 8621499.
25. Dyck JR, Gao G, Widmer J, Stapleton D, Fernandez CS, Kemp BE, et al. Regulation of 5′-AMP-activated protein kinase activity by the noncatalytic beta and gamma subunits. J Biol Chem. 1996; 271(30):17798-803. PMID: 8663446.
26. Woods A, Cheung PC, Smith FC, Davison MD, Scott J, Beri RK, et al. Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro. J Biol Chem. 1996; 271(17):10282-90. PMID: 8626596.
27. Feng Z, Zhang H, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102(23):8204-9. Epub 2005/06/02. doi: 10.1073/pnas.0502857102 PMID: 15928081; PubMed Central PMCID: PMC1142118.
28. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011; 331(6016):456-61. Epub 2011/01/06. doi: 10.1126/science.1196371 PMID: 21205641; PubMed Central PMCID: PMC3030664.
29. Crighton D, Wilkinson S, O'Prey J, Syed N, Smith P, Harrison PR, et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006; 126(1):121-34. Epub 2006/07/15. doi: 10.1016/j.cell.2006.05.034 PMID: 16839881.
30. Zhou Y, Sun K, Ma Y, Yang H, Zhang Y, Kong X, et al. Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and Bim in hepatocellular carcinoma cells. Scientific reports. 2014; 4:5382. Epub 2014/06/21. doi: 10.1038/srep05382 PMID: 24947039; PubMed Central PMCID: PMCPMC4064348.
31. Suman S, Das TP, Reddy R, Nyakeriga AM, Luevano JE, Konwar D, et al. The pro-apoptotic role of autophagy in breast cancer. Br J Cancer. 2014. Epub 2014/06/20. doi: 10.1038/bjc.2014.203 PMID: 24945999.
32. Marvaso G, Barone A, Amodio N, Raimondi L, Agosti V, Altomare E, et al. Sphingosine analog fingolimod (FTY720) increases radiation sensitivity of human breast cancer cells in vitro. Cancer Biol Ther. 2014; 15(6):797-805. Epub 2014/03/25. doi: 10.4161/cbt.28556 PMID: 24657936; PubMed Central PMCID: PMCPMC4049795.
33. Komatsu S, Moriya S, Che XF, Yokoyama T, Kohno N, Miyazawa K. Combined treatment with SAHA, bortezomib, and clarithromycin for concomitant targeting of aggresome formation and intracellular proteolytic pathways enhances ER stress-mediated cell death in breast cancer cells. Biochem Biophys Res Commun. 2013; 437(1):41-7. Epub 2013/06/25. doi: 10.1016/j.bbrc.2013.06.032 PMID: 23792097.