Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo

Oncotarget

Volumn 7, Issue 23, 2016, Pages 33512-33528

  Karpel Massler, Georg ^a   Ramani, Doruntina ^a   Shu, Chang ^a   Halatsch, Marc Eric ^c   Westhoff, Mike Andrew ^c   Bruce, Jeffrey N ^b   Canoll, Peter ^a   Siegelin, Markus D ^a  

^a Department of Medicine   (United States)

^b NONE   (United States)

^c UNIVERSITY OF ULM   (Germany)

Author keywords

ABT263; Apoptosis; Glioblastoma; L asparaginase; TRAIL

Indexed keywords

ASPARAGINE; CASPASE; DEUBIQUITINASE; NAVITOCLAX; PROTEIN BAK; PROTEIN BAX; PROTEIN MCL 1; PROTEIN NOXA; PROTEIN USP9X; RECOMBINANT ASPARAGINASE; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; ANILINE DERIVATIVE; ANTINEOPLASTIC AGENT; ASPARAGINASE; SULFONAMIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CANCER RESISTANCE; CHEMOSENSITIVITY; CONTROLLED STUDY; DOWN REGULATION; DRUG POTENCY; DRUG POTENTIATION; ENZYME ACTIVATION; ESCHERICHIA COLI; GLIOBLASTOMA CELL LINE; GLIOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MITOCHONDRIAL MEMBRANE POTENTIAL; MONOTHERAPY; MOUSE; NONHUMAN; RNA INTERFERENCE; TRANSCRIPTION REGULATION; UPREGULATION; ANIMAL; BRAIN TUMOR; CELL PROLIFERATION; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GLIOBLASTOMA; METABOLISM; PATHOLOGY; SCID MOUSE; TUMOR CELL LINE;

ANILINE COMPOUNDS; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; ASPARAGINASE; BRAIN NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; GLIOBLASTOMA; HUMANS; MICE; MICE, SCID; SULFONAMIDES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84973620882     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9257     Document Type: Article

References (58)

1. Alberghina L and Gaglio D. Redox control of glutamine utilization in cancer. Cell Death Dis. 2014; 5:e1561.
2. Qiu F, Huang J and Sui M. Targeting arginine metabolism pathway to treat arginine-dependent cancers. Cancer Lett. 2015; 364:1-7.
3. Seyfried TN, Flores R, Poff AM, D'Agostino DP and Mukherjee P. Metabolic therapy: a new paradigm for managing malignant brain cancer. Cancer Lett. 2015; 356:289-300.
4. Zhang J, Fan J, Venneti S, Cross JR, Takagi T, Bhinder B, Djaballah H, Kanai M, Cheng EH, Judkins AR, Pawel B, Baggs J, Cherry S, Rabinowitz JD and Thompson CB. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell. 2014; 56:205-218.
5. Henriksen LT, Harila-Saari A, Ruud E, Abrahamsson J, Pruunsild K, Vaitkeviciene G, Jonsson OG, Schmiegelow K, Heyman M, Schroder H, Albertsen BK, Nordic Society of Paediatric H aematology and Oncology (NOPHO) group. PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol. Pediatr Blood Cancer. 2015; 62:427-433.
6. Li BS, Gu LJ, Luo CY, Li WS, Jiang LM, Shen SH, Jiang H, Shen SH, Zhang B, Chen J, Xue HL and Tang JY. The downregulation of asparagine synthetase expression can increase the sensitivity of cells resistant to l-asparaginase. Leukemia. 2006; 20:2199-2201.
7. Ben Tanfous M, Sharif-Askari B, Ceppi F, Laaribi H, Gagne V, Rousseau J, Labuda M, Silverman LB, Sallan SE, Neuberg D, Kutok JL, Sinnett D, Laverdiere C and Krajinovic M. Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia. Clin Cancer Res. 2015; 21:329-334.
8. Rousseau J, Gagne V, Labuda M, Beaubois C, Sinnett D, Laverdiere C, Moghrabi A, Sallan SE, Silverman LB, Neuberg D, Kutok JL and Krajinovic M. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia. Blood. 2011; 118:5883-5890.
9. Bachet JB, Gay F, Marechal R, Galais MP, Adenis A, Ms CD, Cros J, Demetter P, Svrcek M, Bardier-Dupas A, Emile JF, Hammel P, Ebenezer C, Berlier W, Godfrin Y and Andre T. Asparagine synthetase expression and phase I study with L-asparaginase encapsulated in red blood cells in patients with pancreatic adenocarcinoma. Pancreas. 2015; 44:1141-1147.
10. Balasubramanian MN, Butterworth EA and Kilberg MS. Asparagine synthetase: regulation by cell stress and involvement in tumor biology. Am J Physiol Endocrinol Metab. 2013; 304:E789-799.
11. Chien WW, Le Beux C, Rachinel N, Julien M, Lacroix CE, Allas S, Sahakian P, Cornut-Thibaut A, Lionnard L, Kucharczak J, Aouacheria A, Abribat T and Salles G. Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines. Sci Rep. 2015; 5:8068.
12. Borad MJ, Babiker HM, Anthony S, Mita M, Buchbinder A, Keilani T and Grem J. A multicenter, open-label, Phase 1 study evaluating the safety and tolerability of pegaspargase in combination with gemcitabine in advanced metastatic solid tumors and lymphoma. Cancer Invest. 2015; 33:172-179.
13. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352:987-996.
14. Sandmann T, Bourgon R, Garcia J, Li C, Cloughesy T, Chinot OL, Wick W, Nishikawa R, Mason W, Henriksson R, Saran F, Lai A, Moore N, Kharbanda S, Peale F, Hegde P, et al. Patients with proneural glioblastoma may derive overall survival benefit from the addition of Bevacizumab to first-line radiotherapy and temozolomide: Retrospective analysis of the AVAglio trial. J Clin Oncol. 2015; 33:2735-2744.
15. Pavlova NN and Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016; 23:27-47.
16. Vander Heiden MG, Cantley LC and Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324:1029-1033.
17. Yang C, Sudderth J, Dang T, Bachoo RM, McDonald JG and DeBerardinis RJ. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res. 2009; 69:7986-7993.
18. Dranoff G, Elion GB, Friedman HS and Bigner DD. Combination chemotherapy in vitro exploiting glutamine metabolism of human glioma and medulloblastoma. Cancer Res. 1985; 45:4082-4086.
19. Styczynski J, Olszewska-Slonina D, Kolodziej B, Napieraj M and Wysocki M. Activity of bortezomib in glioblastoma. Anticancer Res. 2006; 26:4499-4503.
20. Cheng T, Sudderth J, Yang C, Mullen AR, Jin ES, Mates JM and DeBerardinis RJ. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci U S A. 2011; 108:8674-8679.
21. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB and Thompson CB. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A. 2008; 105:18782-18787.
22. Salzer WL, Asselin BL, Plourde PV, Corn T and Hunger SP. Development of asparaginase Erwinia chrysanthemi for the treatment of acute lymphoblastic leukemia. Ann N Y Acad Sci. 2014; 1329:81-92.
23. Chan WK, Lorenzi PL, Anishkin A, Purwaha P, Rogers DM, Sukharev S, Rempe SB and Weinstein JN. The glutaminase activity of L-asparaginase is not required for anticancer activity against ASNS-negative cells. Blood. 2014; 123:3596-3606.
24. Panosyan EH, Wang Y, Xia P, Lee WN, Pak Y, Laks DR, Lin HJ, Moore TB, Cloughesy TF, Kornblum HI and Lasky JL, 3rd. Asparagine depletion potentiates the cytotoxic effect of chemotherapy against brain tumors. Mol Cancer Res. 2014; 12:694-702.
25. High LM, Szymanska B, Wilczynska-Kalak U, Barber N, O'Brien R, Khaw SL, Vikstrom IB, Roberts AW and Lock RB. The Bcl-2 homology domain 3 mimetic ABT-737 targets the apoptotic machinery in acute lymphoblastic leukemia resulting in synergistic in vitro and in vivo interactions with established drugs. Mol Pharmacol. 2010; 77:483-494.
26. Kang MH, Kang YH, Szymanska B, Wilczynska-Kalak U, Sheard MA, Harned TM, Lock RB and Reynolds CP. Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo. Blood. 2007; 110:2057-2066.
27. Song P, Ye L, Fan J, Li Y, Zeng X, Wang Z, Wang S, Zhang G, Yang P, Cao Z and Ju D. Asparaginase induces apoptosis and cytoprotective autophagy in chronic myeloid leukemia cells. Oncotarget. 2015; 6:3861-3873. doi:10.18632/oncotarget.2869.
28. Hetschko H, Voss V, Horn S, Seifert V, Prehn JH and Kogel D. Pharmacological inhibition of Bcl-2 family members reactivates TRAIL-induced apoptosis in malignant glioma. J Neurooncol. 2008; 86:265-272.
29. Murphy AC, Weyhenmeyer B, Noonan J, Kilbride SM, Schimansky S, Loh KP, Kogel D, Letai AG, Prehn JH and Murphy BM. Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. Apoptosis. 2014; 19:629-642.
30. Haag C, Stadel D, Zhou S, Bachem MG, Moller P, Debatin KM and Fulda S. Identification of c-FLIP(L) and c-FLIP(S) as critical regulators of death receptor-induced apoptosis in pancreatic cancer cells. Gut. 2011; 60:225-237.
31. Morle A, Garrido C and Micheau O. Hyperthermia restores apoptosis induced by death receptors through aggregationinduced c-FLIP cytosolic depletion. Cell Death Dis. 2015; 6:e1633.
32. Liu Y, Hawkins OE, Vilgelm AE, Pawlikowski JS, Ecsedy JA, Sosman JA, Kelley MC and Richmond A. Combining an aurora kinase inhibitor and a death receptor ligand/agonist antibody triggers apoptosis in melanoma cells and prevents tumor growth in peclinical mouse models. Clin Cancer Res. 2015; 21:5338-5348.
33. Pareja F, Macleod D, Shu C, Crary JF, Canoll PD, Ross AH and Siegelin MD. PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD. Mol Cancer Res. 2014; 12:987-1001.
34. Wolfsperger F, Hogh-Binder SA, Schittenhelm J, Psaras T, Ritter V, Bornes L, Huber SM, Jendrossek V and Rudner J. Deubiquitylating enzyme USP9x regulates radiosensitivity in glioblastoma cells by Mcl-1-dependent and-independent mechanisms. Cell Death Dis. 2016; 7:e2039.
35. Amarante-Mendes GP and Griffith TS. Therapeutic applications of TRAIL receptor agonists in cancer and beyond. Pharmacol Ther. 2015; 155:117-131.
36. Fulda S. Safety and tolerability of TRAIL receptor agonists in cancer treatment. Eur J Clin Pharmacol. 2015; 71:525-527.
37. Fulda S. Targeting extrinsic apoptosis in cancer: Challenges and opportunities. Semin Cell Dev Biol. 2015; 39:20-25.
38. Lemke J, von Karstedt S, Zinngrebe J and Walczak H. Getting TRAIL back on track for cancer therapy. Cell Death Differ. 2014; 21:1350-1364.
39. Allen JE, Krigsfeld G, Mayes PA, Patel L, Dicker DT, Patel AS, Dolloff NG, Messaris E, Scata KA, Wang W, Zhou JY, Wu GS and El-Deiry WS. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci Transl Med. 2013; 5:171ra117.
40. Greer YE and Lipkowitz S. TIC10/ONC201: a bend in the road to clinical development. Oncoscience. 2015; 2:75-76. doi:10.18632/oncoscience.133.
41. Karpel-Massler G, Ba M, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P and Siegelin MD. TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo. Oncotarget. 2015; 6:36456-36471. doi:10.18632/oncotarget.5505.
42. Willems L, Jacque N, Jacquel A, Neveux N, Maciel TT, Lambert M, Schmitt A, Poulain L, Green AS, Uzunov M, Kosmider O, Radford-Weiss I, Moura IC, Auberger P, Ifrah N, Bardet V, et al. Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia. Blood. 2013; 122:3521-3532.
43. Akgul C, Moulding DA, White MR and Edwards SW. In vivo localisation and stability of human Mcl-1 using green fluorescent protein (GFP) fusion proteins. FEBS Lett. 2000; 478:72-76.
44. Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, Maecker H, O'Rourke K, Bazan F, Eastham-Anderson J, Yue P, Dornan D, Huang DC and Dixit VM. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010; 463:103-107.
45. Armstrong JL, Flockhart R, Veal GJ, Lovat PE and Redfern CP. Regulation of endoplasmic reticulum stress-induced cell death by ATF4 in neuroectodermal tumor cells. J Biol Chem. 2010; 285:6091-6100.
46. Schuler M, Maurer U, Goldstein JC, Breitenbucher F, Hoffarth S, Waterhouse NJ and Green DR. p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation. Cell Death Differ. 2003; 10:451-460.
47. Ishii N, Maier D, Merlo A, Tada M, Sawamura Y, Diserens AC and Van Meir EG. Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol. 1999; 9:469-479.
48. Sonabend AM, Yun J, Lei L, Leung R, Soderquist C, Crisman C, Gill BJ, Carminucci A, Sisti J, Castelli M, Sims PA, Bruce JN and Canoll P. Murine cell line model of proneural glioma for evaluation of anti-tumor therapies. J Neurooncol. 2013; 112:375-382.
49. Karpel-Massler G, Westhoff MA, Zhou S, Nonnenmacher L, Dwucet A, Kast RE, Bachem MG, Wirtz CR, Debatin KM and Halatsch ME. Combined inhibition of HER1/EGFR and RAC1 results in a synergistic antiproliferative effect on established and primary cultured human glioblastoma cells. Mol Cancer Ther. 2013; 12:1783-1795.
50. Carlson BL, Pokorny JL, Schroeder MA and Sarkaria JN. Establishment, maintenance and in vitro and in vivo applications of primary human glioblastoma multiforme (GBM) xenograft models for translational biology studies and drug discovery. Curr Protoc Pharmacol. 2011; Chapter 14:Unit 14 16.
51. Karpel-Massler G, Kast RE, Westhoff MA, Dwucet A, Welscher N, Nonnenmacher L, Hlavac M, Siegelin MD, Wirtz CR, Debatin KM and Halatsch ME. Olanzapine inhibits proliferation, migration and anchorage-independent growth in human glioblastoma cell lines and enhances temozolomide's antiproliferative effect. J Neurooncol. 2015; 122:21-33.
52. Karpel-Massler G, Westhoff MA, Kast RE, Dwucet A, Nonnenmacher L, Wirtz CR, Debatin KM and Halatsch ME. Artesunate enhances the antiproliferative effect of temozolomide on U87MG and A172 glioblastoma cell lines. Anticancer Agents Med Chem. 2014; 14:313-318.
53. Karpel-Massler G, Ba M, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P and Siegelin MD. TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo. Oncotarget. 2015; 6:36456-71. doi: 10.18632/oncotarget.5505.
54. Karpel-Massler G, Pareja F, Aime P, Shu C, Chau L, Westhoff MA, Halatsch ME, Crary JF, Canoll P and Siegelin MD. PARP inhibition restores extrinsic apoptotic sensitivity in glioblastoma. PLoS One. 2014; 9:e114583.
55. Siegelin MD, Dohi T, Raskett CM, Orlowski GM, Powers CM, Gilbert CA, Ross AH, Plescia J and Altieri DC. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J Clin Invest. 2011; 121:1349-1360.
56. Karpel-Massler G, Shu C, Chau L, Banu M, Halatsch ME, Westhoff MA, Ramirez Y, Ross AH, Bruce JN, Canoll P and Siegelin MD. Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo. Oncotarget. 2015; 6:14507-14521. doi:10.18632/oncotarget.3993.
57. Swain AL, Jaskolski M, Housset D, Rao JK and Wlodawer A. Crystal structure of Escherichia coli L-asparaginase, an enzyme used in cancer therapy. Proc Natl Acad Sci U S A. 1993; 90:1474-1478.
58. Karpel-Massler G, Horst BA, Shu C, Chau L, Tsujiuchi T, Bruce JN, Canoll P, Greene LA, Angelastro JM and Siegelin MD. A synthetic cell-penetrating dominantnegative ATF5 peptide exerts anti-cancer activity against a broad spectrum of treatment-resistant cancers. Clin Cancer Res. 2016; Epub ahead of print.