Temozolomide toxicity operates in a xCT/SLC7a11 dependent manner and is fostered by ferroptosis

Oncotarget

Volumn 7, Issue 46, 2016, Pages 74630-74647

  Sehm, Tina ^a   Rauh, Manfred ^a   Wiendieck, Kurt ^b   Buchfelder, Michael ^a   Eyüpoglu, IIker Y ^a   Savaskan, Nicolai E ^a,c  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b Kliniken Dr Erler   (Germany)

^c BiMECON Ent   (Germany)

Author keywords

Apoptosis; Brain tumor; Cell death; Ferroptosis; Glioma niche

Indexed keywords

ANTINEOPLASTIC AGENT; ERASTIN; SALAZOSULFAPYRIDINE; SLC7A11 PROTEIN; SORAFENIB; TEMOZOLOMIDE; TUMOR PROTEIN; UNCLASSIFIED DRUG; ALKYLATING AGENT; AMINO ACID TRANSPORTER; CARBANILAMIDE DERIVATIVE; DACARBAZINE; NICOTINAMIDE; PIPERAZINE DERIVATIVE; SLC7A11 PROTEIN, HUMAN;

ANIMAL CELL; APOPTOSIS; ARTICLE; ASTROCYTE; CELL DEATH; CELL SURVIVAL; CELL VIABILITY; CHEMOSENSITIVITY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG DETERMINATION; DRUG EFFICACY; FERROPTOSIS; GLIOMA; HUMAN; HUMAN CELL; IC50; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; RAT; RNA INTERFERENCE; ANALOGS AND DERIVATIVES; ANIMAL; AUTOPHAGY; CELL CYCLE CHECKPOINT; DRUG EFFECTS; DRUG POTENTIATION; DRUG RESISTANCE; GENE EXPRESSION; GENE KNOCKDOWN; GENETICS; METABOLISM; MOUSE; PYRAMIDAL NERVE CELL; TUMOR CELL LINE;

AMINO ACID TRANSPORT SYSTEM Y+; ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; APOPTOSIS; ASTROCYTES; AUTOPHAGY; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CELL SURVIVAL; DACARBAZINE; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; GENE EXPRESSION; GENE KNOCKDOWN TECHNIQUES; GLIOMA; HUMANS; MICE; NIACINAMIDE; PHENYLUREA COMPOUNDS; PIPERAZINES; PYRAMIDAL CELLS; RATS;

EID: 84996807781     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.11858     Document Type: Article

References (34)

1. Eyupoglu IY, Buchfelder M, Savaskan NE. Surgical resection of malignant gliomas-role in optimizing patient outcome. Nature reviews Neurology. 2013; 9:141-51.
2. Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. Jama. 2013; 310:1842-50.
3. D'Atri S, Tentori L, Lacal PM, Graziani G, Pagani E, Benincasa E, Zambruno G, Bonmassar E, Jiricny J. Involvement of the mismatch repair system in temozolomide-induced apoptosis. Molecular pharmacology. 1998; 54:334-41.
4. Chen L, Li X, Liu L, Yu B, Xue Y, Liu Y. Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and cystathionine-gamma-lyase function. Oncology reports. 2015; 33:1465-74.
5. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B, 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012; 149:1060-72.
6. Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death. Nature chemical biology. 2014; 10:9-17.
7. Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS, Stockwell BR. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife. 2014; 3:e02523.
8. Savaskan NE, Heckel A, Hahnen E, Engelhorn T, Doerfler A, Ganslandt O, Nimsky C, Buchfelder M, Eyupoglu IY. Small interfering RNA-mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema. Nature medicine. 2008; 14:629-32.
9. Robert SM, Buckingham SC, Campbell SL, Robel S, Holt KT, Ogunrinu-Babarinde T, Warren PP, White DM, Reid MA, Eschbacher JM, Berens ME, Lahti AC, Nabors LB, et al. SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Science translational medicine. 2015; 7:289ra86.
10. Patel D, Kharkar PS, Nandave M. Emerging roles of system [Formula: see text] antiporter and its inhibition in CNS disorders. Molecular membrane biology. 2015; 32:89-116.
11. Savaskan NE, Eyupoglu IY. xCT modulation in gliomas: relevance to energy metabolism and tumor microenvironment normalization. Annals of anatomy. 2010; 192:309-13.
12. Chung WJ, Sontheimer H. Sulfasalazine inhibits the growth of primary brain tumors independent of nuclear factor-kappaB. Journal of neurochemistry. 2009; 110:182-93.
13. Gores GJ. Decade in review-hepatocellular carcinoma: HCC-subtypes, stratification and sorafenib. Nature reviews Gastroenterology & hepatology. 2014; 11:645-7.
14. Sio TT, Ko J, Gudena VK, Verma N, Chaudhary UB. Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a comprehensive review. International journal of urology. 2014; 21:630-7.
15. Homma T, Fujii J. Application of Glutathione as Anti-Oxidative and Anti-Aging Drugs. Current drug metabolism. 2015; 16:560-71.
16. Savaskan NE, Fan Z, Broggini T, Buchfelder M, Eyupoglu IY. Neurodegeneration in the Brain Tumor Microenvironment: Glutamate in the Limelight. Current neuropharmacology. 2015; 13:258-65.
17. Lyons SA, Chung WJ, Weaver AK, Ogunrinu T, Sontheimer H. Autocrine glutamate signaling promotes glioma cell invasion. Cancer research. 2007; 67:9463-71.
18. Buckingham SC, Campbell SL, Haas BR, Montana V, Robel S, Ogunrinu T, Sontheimer H. Glutamate release by primary brain tumors induces epileptic activity. Nature medicine. 2011; 17:1269-74.
19. Savaskan NE, Hahnen E, Eyupoglu IY. The x(c)(-) cystine/glutamate antiporter (xCT) as a potential target for therapy of cancer: yet another cytotoxic anticancer approach? Journal of cellular physiology. 2009; 220:531-2; author reply 3-4.
20. Ye ZC, Sontheimer H. Glioma cells release excitotoxic concentrations of glutamate. Cancer research. 1999; 59:4383-91.
21. Dai L, Cao Y, Chen Y, Kaleeba JA, Zabaleta J, Qin Z. Genomic analysis of xCT-mediated regulatory network: Identification of novel targets against AIDS-associated lymphoma. Oncotarget. 2015; 6:12710-22. doi: 10.18632/oncotarget.3710.
22. Timmerman LA, Holton T, Yuneva M, Louie RJ, Padro M, Daemen A, Hu M, Chan DA, Ethier SP, van 't Veer LJ, Polyak K, McCormick F, Gray JW. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer cell. 2013; 24:450-65.
23. Yae T, Tsuchihashi K, Ishimoto T, Motohara T, Yoshikawa M, Yoshida GJ, Wada T, Masuko T, Mogushi K, Tanaka H, Osawa T, Kanki Y, Minami T, et al. Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell. Nature communications. 2012; 3:883.
24. Chamberlain MC, Bota DA, Linskey ME, Schwartz PH. Neural stem/progenitors and glioma stem-like cells have differential sensitivity to chemotherapy. Neurology. 2011; 77:e135; author reply e-6.
25. Parisi S, Corsa P, Raguso A, Perrone A, Cossa S, Munafo T, Sanpaolo G, Donno E, Clemente MA, Piombino M, Parisi F, Valle G. Temozolomide and radiotherapy versus radiotherapy alone in high grade gliomas: a very long term comparative study and literature review. BioMed research international. 2015; 2015:620643.
26. Yang LJ, Zhou CF, Lin ZX. Temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme: a systematic review. Cancer investigation. 2014; 32:31-6.
27. Zhang D, Tang B, Xie X, Xiao YF, Yang SM, Zhang JW. The interplay between DNA repair and autophagy in cancer therapy. Cancer biology & therapy. 2015; 16:1005-13.
28. Zhang WB, Wang Z, Shu F, Jin YH, Liu HY, Wang QJ, Yang Y. Activation of AMP-activated protein kinase by temozolomide contributes to apoptosis in glioblastoma cells via p53 activation and mTORC1 inhibition. J Biol Chem. 2010; 285:40461-71.
29. Ui-Tei K, Naito Y, Takahashi F, Haraguchi T, Ohki-Hamazaki H, Juni A, Ueda R, Saigo K. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic acids research. 2004; 32:936-48.
30. Hatipoglu G, Hock SW, Weiss R, Fan Z, Sehm T, Ghoochani A, Buchfelder M, Savaskan NE, Eyupoglu IY. Sunitinib impedes brain tumor progression and reduces tumor-induced neurodegeneration in the microenvironment. Cancer science. 2015; 106:160-70.
31. Ghoochani A, Yakubov E, Sehm T, Fan Z, Hock S, Buchfelder M, Eyupoglu IY, Savaskan NE. A versatile ex vivo technique for assaying tumor angiogenesis and microglia in the brain. Oncotarget. 2015; 7:1838-53. doi: 10.18632/oncotarget.6550.
32. Welzel O, Tischbirek CH, Jung J, Kohler EM, Svetlitchny A, Henkel AW, Kornhuber J, Groemer TW. Synapse clusters are preferentially formed by synapses with large recycling pool sizes. PloS one. 2010; 5:e13514.
33. Fan Z, Sehm T, Rauh M, Buchfelder M, Eyupoglu IY, Savaskan NE. Dexamethasone alleviates tumor-associated brain damage and angiogenesis. PloS one. 2014; 9:e93264.
34. Sehm T, Fan Z, Ghoochani A, Rauh M, Engelhorn T, Minakaki G, Dörfler A, Klucken J, Buchfelder M, Eyüpoglu IY, Savaskan, N. Sulfasalazine impacts on ferroptotic cell death and alleviates the tumor microenvironment and glioma-induced brain edema. Oncotarget 2016; doi: 10.18632/oncotarget.8651.