Inhibition of prostaglandin reductase 2, a putative oncogene overexpressed in human pancreatic adenocarcinoma, induces oxidative stress-mediated cell death involving xCT and CTH gene expressions through 15-keto-PGE2

PLoS ONE

Volumn 11, Issue 1, 2016, Pages

  Chang, Emily Yun Chia ^a   Chang, Yi Cheng ^a,b,c   Shun, Chia Tung ^a   Tien, Yu Wen ^a   Tsai, Shu Huei ^d   Hee, Siow Wey ^a   Chen, Ing Jung ^e   Chuang, Lee Ming ^a,e  

^a NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^c INSTITUTE OF BIOMEDICAL SCIENCES   (Taiwan)

^d BRITISH COLUMBIA CANCER AGENCY   (Canada)

^e NATIONAL TAIWAN UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTATHIONINE GAMMA LYASE; GLUTATHIONE; OXIDOREDUCTASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PROSTAGLANDIN REDUCTASE 2; UNCLASSIFIED DRUG; 15-KETOPROSTAGLANDIN E2; ALCOHOL DEHYDROGENASE; AMINO ACID TRANSPORTER; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROSTAGLANDIN E2; PTGR2 PROTEIN, HUMAN; REACTIVE OXYGEN METABOLITE; SLC7A11 PROTEIN, HUMAN;

ARTICLE; CARCINOGENESIS; CELL DEATH; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; CTH GENE; ENZYME INHIBITION; GENE; GENE OVEREXPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; MAJOR CLINICAL STUDY; MOLECULAR PATHOLOGY; ONCOGENE; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PANCREAS ADENOCARCINOMA; PROTEIN EXPRESSION; PROTEIN FUNCTION; XCT GENE; ANALOGS AND DERIVATIVES; APOPTOSIS; CELL SURVIVAL; ENZYMOLOGY; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PANCREAS CARCINOMA; PANCREAS TUMOR; PHYSIOLOGY; TUMOR CELL LINE;

ALCOHOL DEHYDROGENASE; AMINO ACID TRANSPORT SYSTEM Y+; APOPTOSIS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CYSTATHIONINE GAMMA-LYASE; DINOPROSTONE; GENE EXPRESSION; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE KNOCKDOWN TECHNIQUES; GLUTATHIONE; HUMANS; OXIDATIVE STRESS; PANCREATIC NEOPLASMS; PPAR GAMMA; REACTIVE OXYGEN SPECIES;

EID: 84958787547     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0147390     Document Type: Article

References (76)

1. Eibl G, Takata Y, Boros LG, Liu J, Okada Y, Reber HA, et al. Growth stimulation of COX-2-negative pancreatic cancer by a selective COX-2 inhibitor. Cancer Res. 2005; 65(3):982-90. PMID: 15705899
2. Yamaue H, Satoi S, Kanbe T, Miyazawa M, Tani M, Kawai M, et al. Phase II clinical study of alternateday oral therapy with S-1 as first-line chemotherapy for locally advanced and metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2013.
3. Chu J, Lloyd FL, Trifan OC, Knapp B, Rizzo MT. Potential involvement of the cyclooxygenase-2 pathway in the regulation of tumor-associated angiogenesis and growth in pancreatic cancer. Mol Cancer Ther. 2003; 2(1):1-7. PMID: 12533667
4. Chou WL, Chuang LM, Chou CC, Wang AH, Lawson JA, FitzGerald GA, et al. Identification of a novel prostaglandin reductase reveals the involvement of prostaglandin E2 catabolism in regulation of peroxisome proliferator-activated receptor gamma activation. J Biol Chem. 2007; 282(25):18162-72. PMID: 17449869
5. Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH. Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2. Structure. 2008; 16(11):1714-23. doi: 10. 1016/j.str.2008.09.007 PMID: 19000823
6. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine reviews. 1999; 20(5):649-88. PMID: 10529898
7. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006; 55(1):115-22. PMID: 16118353
8. Wang MT, Honn KV, Nie D. Cyclooxygenases, prostanoids, and tumor progression. Cancer Metastasis Rev. 2007; 26(3-4):525-34. PMID: 17763971
9. Luo S, Wang J, Ma Y, Yao Z, Pan H. PPARgamma inhibits ovarian cancer cells proliferation through upregulation of miR-125b. Biochemical and biophysical research communications. 2015; 462(2):85-90. doi: 10.1016/j.bbrc.2015.04.023 PMID: 25944662
10. Sabatino L, Pancione M, Votino C, Colangelo T, Lupo A, Novellino E, et al. Emerging role of the betacatenin-PPARgamma axis in the pathogenesis of colorectal cancer. World J Gastroenterol. 2014; 20 (23):7137-51. doi: 10.3748/wjg.v20.i23.7137 PMID: 24966585
11. Apostoli AJ, Roche JM, Schneider MM, SenGupta SK, Di Lena MA, Rubino RE, et al. Opposing roles for mammary epithelial-specific PPARgamma signaling and activation during breast tumour progression. Molecular cancer. 2015; 14:85. doi: 10.1186/s12943-015-0347-8 PMID: 25889730
12. Fulzele SV, Chatterjee A, Shaik MS, Jackson T, Ichite N, Singh M. 15-Deoxy-Delta12,14-prostaglandin J2 enhances docetaxel anti-tumor activity against A549 and H460 non-small-cell lung cancer cell lines and xenograft tumors. Anticancer Drugs. 2007; 18(1):65-78. PMID: 17159504
13. Takahashi N, Okumura T, Motomura W, Fujimoto Y, Kawabata I, Kohgo Y. Activation of PPARgamma inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett. 1999; 455(1-2):135-9. PMID: 10428487
14. Leung WK, Bai AH, Chan VY, Yu J, Chan MW, To KF, et al. Effect of peroxisome proliferator activated receptor gamma ligands on growth and gene expression profiles of gastric cancer cells. Gut. 2004; 53 (3):331-8. PMID: 14960510
15. Konturek PC, Kania J, Kukharsky V, Raithel M, Ocker M, Rembiasz K, et al. Implication of peroxisome proliferator-activated receptor gamma and proinflammatory cytokines in gastric carcinogenesis: link to Helicobacter pylori-infection. J Pharmacol Sci. 2004; 96(2):134-43. PMID: 15492468
16. Chen YX, Zhong XY, Qin YF, Bing W, He LZ. 15d-PGJ2 inhibits cell growth and induces apoptosis of MCG-803 human gastric cancer cell line. World J Gastroenterol. 2003; 9(10):2149-53. PMID: 14562367
17. Ma XM, Yu H, Huai N. Peroxisome proliferator-activated receptor-gamma is essential in the pathogenesis of gastric carcinoma. World J Gastroenterol. 2009; 15(31):3874-83. PMID: 19701967
18. Chang EY, Tsai SH, Shun CT, Hee SW, Chang YC, Tsai YC, et al. Prostaglandin reductase 2 modulates ROS-mediated cell death and tumor transformation of gastric cancer cells and is associated with higher mortality in gastric cancer patients. Am J Pathol. 2012; 181(4):1316-26. doi: 10.1016/j.ajpath. 2012.07.006 PMID: 22998775
19. Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013; 12(12):931-47. doi: 10.1038/nrd4002 PMID: 24287781
20. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cellular signalling. 2007; 19(9):1807-19. PMID: 17570640
21. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011; 475(7354):106-9. doi: 10. 1038/nature10189 PMID: 21734707
22. Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X, et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature. 2011; 475(7355):231-4. doi: 10.1038/nature10167 PMID: 21753854
23. Glasauer A, Chandel NS. Targeting antioxidants for cancer therapy. Biochemical pharmacology. 2014.
24. Glasauer A, Sena LA, Diebold LP, Mazar AP, Chandel NS. Targeting SOD1 reduces experimental nonsmall-cell lung cancer. The Journal of clinical investigation. 2014; 124(1):117-28. PMID: 24292713
25. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular aspects of medicine. 2009; 30(1-2):1-12. doi: 10.1016/j.mam.2008.08.006 PMID: 18796312
26. Ishii I, Akahoshi N, Yamada H, Nakano S, Izumi T, Suematsu M. Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. J Biol Chem. 2010; 285(34):26358-68. doi: 10.1074/jbc.M110.147439 PMID: 20566639
27. Leikam C, Hufnagel A, Walz S, Kneitz S, Fekete A, Muller MJ, et al. Cystathionase mediates senescence evasion in melanocytes and melanoma cells. Oncogene. 2014; 33(6):771-82. doi: 10.1038/onc. 2012.641 PMID: 23353821
28. Lee ZW, Low YL, Huang S, Wang T, Deng LW. The cystathionine gamma-lyase/hydrogen sulfide system maintains cellular glutathione status. The Biochemical journal. 2014; 460(3):425-35. doi: 10.1042/BJ20131434 PMID: 24707893
29. Lim JC, Donaldson PJ. Focus on molecules: the cystine/glutamate exchanger (System x(c)(-)). Experimental eye research. 2011; 92(3):162-3. doi: 10.1016/j.exer.2010.05.007 PMID: 20488177
30. Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, et al. The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxidants & redox signaling. 2013; 18(5):522-55.
31. Shiozaki A, Iitaka D, Ichikawa D, Nakashima S, Fujiwara H, Okamoto K, et al. xCT, component of cysteine/glutamate transporter, as an independent prognostic factor in human esophageal squamous cell carcinoma. Journal of gastroenterology. 2014; 49(5):853-63. doi: 10.1007/s00535-013-0847-5 PMID: 23771433
32. Guo W, Zhao Y, Zhang Z, Tan N, Zhao F, Ge C, et al. Disruption of xCT inhibits cell growth via the ROS/autophagy pathway in hepatocellular carcinoma. Cancer Lett. 2011; 312(1):55-61. doi: 10.1016/j. canlet.2011.07.024 PMID: 21906871
33. Dai L, Cao Y, Chen Y, Parsons C, Qin Z. Targeting xCT, a cystine-glutamate transporter induces apoptosis and tumor regression for KSHV/HIV-associated lymphoma. Journal of hematology & oncology. 2014; 7:30.
34. Lo M, Ling V, Wang YZ, Gout PW. The xc-cystine/glutamate antiporter: a mediator of pancreatic cancer growth with a role in drug resistance. Br J Cancer. 2008; 99(3):464-72. doi: 10.1038/sj.bjc.6604485 PMID: 18648370
35. Chung WJ, Lyons SA, Nelson GM, Hamza H, Gladson CL, Gillespie GY, et al. Inhibition of cystine uptake disrupts the growth of primary brain tumors. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2005; 25(31):7101-10.
36. Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer cell. 2011; 19(3):387-400. doi: 10.1016/j.ccr.2011.01.038 PMID: 21397861
37. Lo M, Ling V, Low C, Wang YZ, Gout PW. Potential use of the anti-inflammatory drug, sulfasalazine, for targeted therapy of pancreatic cancer. Current oncology. 2010; 17(3):9-16. PMID: 20567622
38. Robert SM, Buckingham SC, Campbell SL, Robel S, Holt KT, Ogunrinu-Babarinde T, et al. SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Science translational medicine. 2015; 7(289):289ra86. doi: 10.1126/scitranslmed.aaa8103 PMID: 26019222
39. Linher-Melville K, Haftchenary S, Gunning P, Singh G. Signal transducer and activator of transcription 3 and 5 regulate system Xc-and redox balance in human breast cancer cells. Molecular and cellular biochemistry. 2015; 405(1-2):205-21. doi: 10.1007/s11010-015-2412-4 PMID: 25896132
40. Pazienza V, Vinciguerra M, Mazzoccoli G. PPARs Signaling and Cancer in the Gastrointestinal System. PPAR research. 2012; 2012:560846. doi: 10.1155/2012/560846 PMID: 23028383
41. Dong YW, Wang XP, Wu K. Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor gamma involves angiogenesis inhibition. World J Gastroenterol. 2009; 15 (4):441-8. PMID: 19152448
42. Tsujie M, Nakamori S, Okami J, Hayashi N, Hiraoka N, Nagano H, et al. Thiazolidinediones inhibit growth of gastrointestinal, biliary, and pancreatic adenocarcinoma cells through activation of the peroxisome proliferator-activated receptor gamma/retinoid X receptor alpha pathway. Experimental cell research. 2003; 289(1):143-51. PMID: 12941612
43. Kristiansen G, Jacob J, Buckendahl AC, Grutzmann R, Alldinger I, Sipos B, et al. Peroxisome proliferator-activated receptor gamma is highly expressed in pancreatic cancer and is associated with shorter overall survival times. Clinical cancer research: an official journal of the American Association for Cancer Research. 2006; 12(21):6444-51.
44. Lalier L, Cartron PF, Olivier C, Loge C, Bougras G, Robert JM, et al. Prostaglandins antagonistically control Bax activation during apoptosis. Cell death and differentiation. 2011; 18(3):528-37. doi: 10. 1038/cdd.2010.128 PMID: 20966963
45. Srivastava N, Kollipara RK, Singh DK, Sudderth J, Hu Z, Nguyen H, et al. Inhibition of cancer cell proliferation by PPARgamma is mediated by a metabolic switch that increases reactive oxygen species levels. Cell metabolism. 2014; 20(4):650-61. doi: 10.1016/j.cmet.2014.08.003 PMID: 25264247
46. Martindale JL, Holbrook NJ. Cellular response to oxidative stress: signaling for suicide and survival. Journal of cellular physiology. 2002; 192(1):1-15. PMID: 12115731
47. Leikam C, Hufnagel A, Walz S, Kneitz S, Fekete A, Muller MJ, et al. Cystathionase mediates senescence evasion in melanocytes and melanoma cells. Oncogene. 2013.
48. Simons AL, Parsons AD, Foster KA, Orcutt KP, Fath MA, Spitz DR. Inhibition of glutathione and thioredoxin metabolism enhances sensitivity to perifosine in head and neck cancer cells. Journal of oncology. 2009; 2009:519563. doi: 10.1155/2009/519563 PMID: 19746172
49. Goicoechea SM, Garcia-Mata R, Staub J, Valdivia A, Sharek L, McCulloch CG, et al. Palladin promotes invasion of pancreatic cancer cells by enhancing invadopodia formation in cancer-associated fibroblasts. Oncogene. 2013.
50. Omura N, Griffith M, Vincent A, Li A, Hong SM, Walter K, et al. Cyclooxygenase-deficient pancreatic cancer cells use exogenous sources of prostaglandins. Mol Cancer Res. 2010; 8(6):821-32. doi: 10. 1158/1541-7786.MCR-09-0336 PMID: 20530583
51. Yip-Schneider MT, Barnard DS, Billings SD, Cheng L, Heilman DK, Lin A, et al. Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis. 2000; 21(2):139-46. PMID: 10657949
52. Yang Y, Tang LQ, Wei W. Prostanoids receptors signaling in different diseases/cancers progression. Journal of receptor and signal transduction research. 2013; 33(1):14-27. doi: 10.3109/10799893.2012. 752003 PMID: 23327583
53. Liu B, Qu L, Yan S. Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer cell international. 2015; 15:106. doi: 10.1186/s12935-015-0260-7 PMID: 26549987
54. Larsson K, Kock A, Idborg H, Arsenian Henriksson M, Martinsson T, Johnsen JI, et al. COX/mPGES-1/PGE2 pathway depicts an inflammatory-dependent high-risk neuroblastoma subset. Proceedings of the National Academy of Sciences of the United States of America. 2015; 112(26):8070-5. doi: 10. 1073/pnas.1424355112 PMID: 26080408
55. Myung SJ, Rerko RM, Yan M, Platzer P, Guda K, Dotson A, et al. 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103(32):12098-102. PMID: 16880406
56. Tseng-Rogenski S, Gee J, Ignatoski KW, Kunju LP, Bucheit A, Kintner HJ, et al. Loss of 15-hydroxyprostaglandin dehydrogenase expression contributes to bladder cancer progression. Am J Pathol. 2010; 176(3):1462-8. doi: 10.2353/ajpath.2010.090875 PMID: 20093479
57. Ding Y, Tong M, Liu S, Moscow JA, Tai HH. NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. Carcinogenesis. 2005; 26(1):65-72. PMID: 15358636
58. Frank B, Hoeft B, Hoffmeister M, Linseisen J, Breitling LP, Chang-Claude J, et al. Association of hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) variants and colorectal cancer risk. Carcinogenesis. 2011; 32(2):190-6. doi: 10.1093/carcin/bgq231 PMID: 21047993
59. Thiel A, Ganesan A, Mrena J, Junnila S, Nykanen A, Hemmes A, et al. 15-hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2009; 15(14):4572-80.
60. Pham H, Chen M, Li A, King J, Angst E, Dawson DW, et al. Loss of 15-hydroxyprostaglandin dehydrogenase increases prostaglandin E2 in pancreatic tumors. Pancreas. 2010; 39(3):332-9. doi: 10.1097/MPA.0b013e3181baecbe PMID: 19820419
61. Lu D, Han C, Wu T. 15-PGDH inhibits hepatocellular carcinoma growth through 15-keto-PGE2/PPARgamma-mediated activation of p21WAF1/Cip1. Oncogene. 2014; 33(9):1101-12. doi: 10.1038/onc. 2013.69 PMID: 23542179
62. Lu D, Han C, Wu T. 15-hydroxyprostaglandin dehydrogenase-derived 15-keto-prostaglandin E2 inhibits cholangiocarcinoma cell growth through interaction with peroxisome proliferator-activated receptorgamma, SMAD2/3, and TAP63 proteins. J Biol Chem. 2013; 288(27):19484-502. doi: 10.1074/jbc. M113.453886 PMID: 23687300
63. Stravodimou A, Mazzoccoli G, Voutsadakis IA. Peroxisome proliferator-activated receptor gamma and regulations by the ubiquitin-proteasome system in pancreatic cancer. PPAR research. 2012; 2012:367450. doi: 10.1155/2012/367450 PMID: 23049538
64. Eibl G. The Role of PPAR-gamma and Its Interaction with COX-2 in Pancreatic Cancer. PPAR research. 2008; 2008:326915. doi: 10.1155/2008/326915 PMID: 18615182
65. Pazienza V, Tavano F, Benegiamo G, Vinciguerra M, Burbaci FP, Copetti M, et al. Correlations among PPARgamma, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer. PPAR research. 2012; 2012:461784. doi: 10.1155/2012/461784 PMID: 22919364
66. Zhang Y, Luo HY, Liu GL, Wang DS, Wang ZQ, Zeng ZL, et al. Prognostic significance and therapeutic implications of peroxisome proliferator-activated receptor gamma overexpression in human pancreatic carcinoma. International journal of oncology. 2015; 46(1):175-84. doi: 10.3892/ijo.2014.2709 PMID: 25333644
67. Li L, Tao J, Davaille J, Feral C, Mallat A, Rieusset J, et al. 15-deoxy-Delta 12,14-prostaglandin J2 induces apoptosis of human hepatic myofibroblasts. A pathway involving oxidative stress independently of peroxisome-proliferator-activated receptors. J Biol Chem. 2001; 276(41):38152-8. PMID: 11477100
68. Clay CE, Monjazeb A, Thorburn J, Chilton FH, High KP. 15-Deoxy-delta12,14-prostaglandin J2-induced apoptosis does not require PPARgamma in breast cancer cells. Journal of lipid research. 2002; 43(11):1818-28. PMID: 12401880
69. Min KW, Zhang X, Imchen T, Baek SJ. A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4. Toxicology and applied pharmacology. 2012; 263(2):225-32. doi: 10.1016/j.taap.2012. 06.014 PMID: 22750490
70. Hourihan JM, Kenna JG, Hayes JD. The gasotransmitter hydrogen sulfide induces nrf2-target genes by inactivating the keap1 ubiquitin ligase substrate adaptor through formation of a disulfide bond between cys-226 and cys-613. Antioxidants & redox signaling. 2013; 19(5):465-81.
71. Ye P, Mimura J, Okada T, Sato H, Liu T, Maruyama A, et al. Nrf2-and ATF4-dependent upregulation of xCT modulates the sensitivity of T24 bladder carcinoma cells to proteasome inhibition. Molecular and cellular biology. 2014; 34(18):3421-34. doi: 10.1128/MCB.00221-14 PMID: 25002527
72. Yin P, Zhao C, Li Z, Mei C, Yao W, Liu Y, et al. Sp1 is involved in regulation of cystathionine gammalyase gene expression and biological function by PI3K/Akt pathway in human hepatocellular carcinoma cell lines. Cellular signalling. 2012; 24(6):1229-40. doi: 10.1016/j.cellsig.2012.02.003 PMID: 22360859
73. Fujiki K, Inamura H, Matsuoka M. PI3K signaling mediates diverse regulation of ATF4 expression for the survival of HK-2 cells exposed to cadmium. Archives of toxicology. 2014; 88(2):403-14. doi: 10. 1007/s00204-013-1129-y PMID: 24057571
74. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009; 8(7):579-91. doi: 10.1038/nrd2803 PMID: 19478820
75. Ma MZ, Chen G, Wang P, Lu WH, Zhu CF, Song M, et al. Xc-inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism. Cancer Lett. 2015; 368(1):88-96. doi: 10. 1016/j.canlet.2015.07.031 PMID: 26254540
76. Fujiwara N, Inoue J, Kawano T, Tanimoto K, Kozaki K, Inazawa J. miR-634 Activates the Mitochondrial Apoptosis Pathway and Enhances Chemotherapy-Induced Cytotoxicity. Cancer Res. 2015; 75 (18):3890-901. doi: 10.1158/0008-5472.CAN-15-0257 PMID: 26216549