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Original Research

Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells

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Pages 7901-7921 | Published online: 13 Oct 2020

References

  • Handy RD, Von der Kammer F, Lead JR, Hassellöv M, Owen R, Crane M. The ecotoxicology and chemistry of manufactured nanoparticles. Ecotoxicology. 2008;17(4):287–314. doi:10.1007/s10646-008-0199-818351458
  • Govindaraju K, Krishnamoorthy K, Alsagaby SA, Singaravelu G, Premanathan M. Green synthesis of silver nanoparticles for selective toxicity towards cancer cells. IET Nanobiotechnol. 2015;9:325–330. doi:10.1049/iet-nbt.2015.000126647807
  • Ke Y, Al Aboody MS, Alturaiki W, et al. Photosynthesized gold nanoparticles from Catharanthus roseus induces caspase-mediated apoptosis in cervical cancer cells (HeLa). Artif Cells Nanomed Biotechnol. 2019;47:1938–1946. doi:10.1080/21691401.2019.161401731099261
  • Kawata K, Osawa M, Okabe S. In vitro toxicity of silver nanoparticles at noncytotoxic doses to HepG2 human hepatoma cells. Environ Sci Technol. 2009;43:6046–6051. doi:10.1021/es900754q19731716
  • Rajeshkumar S. Anticancer activity of eco-friendly gold nanoparticles against lung and liver cancer cells. J Genetic Eng Biotechnol. 2016;14:195–202. doi:10.1016/j.jgeb.2016.05.007
  • Foldbjerg R, Dang DA, Autrup H. Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol. 2011;85:743–750. doi:10.1007/s00204-010-0545-520428844
  • Gurunathan S, Han JW, Eppakayala V, Jeyaraj M, Kim J-H. Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells. Biomed Res Int. 2013;2013.
  • Jiang J, Pi J, Cai J. The advancing of zinc oxide nanoparticles for biomedical applications. Bioinorg Chem Appl. 2018;2018.
  • Premanathan M, Karthikeyan K, Jeyasubramanian K, Manivannan G. Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomed Nanotechnol Biol Med. 2011;7:184–192. doi:10.1016/j.nano.2010.10.001
  • Boroumand Moghaddam A, Moniri M, Azizi S, et al. Eco-friendly formulated zinc oxide nanoparticles: induction of cell cycle arrest and apoptosis in the MCF-7 cancer cell line. Genes. 2017;8:281.
  • Cao Y, Roursgaard M, Kermanizadeh A, Loft S, Møller P. Synergistic effects of zinc oxide nanoparticles and fatty acids on toxicity to caco-2 cells. Int J Toxicol. 2015;34(1):67–76. doi:10.1177/109158181456003225421740
  • Akhtar MJ, Ahamed M, Kumar S, Khan MAM, Ahmad J, Alrokayan SA. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int J Nanomedicine. 2012;7:845.22393286
  • Bai D-P, Zhang X-F, Zhang G-L, Huang Y-F, Gurunathan S. Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells. Int J Nanomedicine. 2017;12:6521. doi:10.2147/IJN.S14007128919752
  • Pandurangan M, Enkhtaivan G, Kim DH. Anticancer studies of synthesized ZnO nanoparticles against human cervical carcinoma cells. J Photochem Photobiol B Biol. 2016;158:206–211. doi:10.1016/j.jphotobiol.2016.03.002
  • Bisht G, Rayamajhi S. ZnO nanoparticles: a promising anticancer agent. Nanobiomedicine. 2016;3:3–9. doi:10.5772/6343729942378
  • Shen C, James SA, de Jonge MD, Turney TW, Wright PFA, Feltis BN. Relating cytotoxicity, zinc ions, and reactive oxygen in ZnO nanoparticle–exposed human immune cells. Toxicol Sci. 2013;136:120–130.23997113
  • Manke A, Wang L, Rojanasakul Y. Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed Res Int. 2013;2013.
  • Lowe R, Shirley N, Bleackley M, Dolan S, Shafee T. Transcriptomics technologies. PLoS Comput Biol. 2017;13.
  • Hanagata N, Xu M, Takemura T, Zhuang F. Cellular response to ZnO nanoparticle toxicity inferred from global gene expression profiles. Nano Biomedicine. 2010;2:153–169.
  • Moos PJ, Olszewski K, Honeggar M, et al. Responses of human cells to ZnO nanoparticles: a gene transcription study. Metallomics. 2011;3:1199–1211.21769377
  • Poon W-L, Alenius H, Ndika J, et al. Nano-sized zinc oxide and silver, but not titanium dioxide, induce innate and adaptive immunity and antiviral response in differentiated THP-1 cells. Nanotoxicology. 2017;11:936–951. doi:10.1080/17435390.2017.138260028958187
  • Tuomela S, Autio R, Buerki-Thurnherr T, et al. Gene expression profiling of immune-competent human cells exposed to engineered zinc oxide or titanium dioxide nanoparticles. PLoS One. 2013;8.
  • Lozzio CB, Lozzio BB. Human Chronic Myelogenous Leukemia Cell-Line with Positive Philadelphia Chromosome. 1975.
  • Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol. 2018;93:442–459.29411417
  • An X, Tiwari AK, Sun Y, Ding P-R, Ashby CR Jr, Chen Z-S. BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. Leuk Res. 2010;34(10):1255–1268. doi:10.1016/j.leukres.2010.04.01620537386
  • Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417.17151364
  • Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917–927. doi:10.1056/NEJMoa160932428273028
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1–2):55–63. doi:10.1016/0022-1759(83)90303-46606682
  • Reimand J, Arak T, Adler P, et al. g: profiler—a web server for functional interpretation of gene lists (2016 update). Nucleic Acids Res. 2016;44:W83–W89. doi:10.1093/nar/gkw19927098042
  • Triboulet S, Aude-Garcia C, Armand L, et al. Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach. Nanoscale. 2014;6:6102–611424788578
  • Mishra PK, Mishra H, Ekielski A, Talegaonkar S, Vaidya B. Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications. Drug Discov Today. 2017;22(12):1825–1834. doi:10.1016/j.drudis.2017.08.00628847758
  • Si M, Lang J. The roles of metallothioneins in carcinogenesis. J Hematol Oncol. 2018;11:107.30139373
  • Dua P, Chaudhari KN, Lee C-H, et al. Evaluation of toxicity and gene expression changes triggered by oxide nanoparticles. Bull Korean Chem Soc. 2011;32(6):2051–2057. doi:10.5012/bkcs.2011.32.6.2051
  • Lee SH, Pie J-E, Kim Y-R, Lee HR, Son SW, Kim M-K. Effects of zinc oxide nanoparticles on gene expression profile in human keratinocytes. Mol Cell Toxicol. 2012;8(2):113–118. doi:10.1007/s13273-012-0014-8
  • Zheng Y, Jiang L, Hu Y, et al. Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway. BMC Cancer. 2017;17:161. doi:10.1186/s12885-017-3139-228241806
  • Liu Z. Ye, Q., Wu, L., et al. Metallothionein 1 family profiling identifies MT1X as a tumor suppressor involved in the progression and metastastatic capacity of hepatocellular carcinoma. Mol Carcinog. 2018;57:1435–1444. doi:10.1002/mc.2284629873415
  • Wang Y, Wang, G, Tan, X, et al. MT1G serves as a tumor suppressor in hepatocellular carcinoma by interacting with p53. Oncogenesis. 2019;8:1–11. doi:10.1038/s41389-019-0176-530631034
  • Mao J, Yu H, Wang C, et al. Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas. Carcinogenesis. 2012;33:2568–2577. doi:10.1093/carcin/bgs28722971577
  • Han YC, Zheng ZL, Zuo ZH, et al. Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1. J Pathol. 2013;230:184–193.23355073
  • Demidenko R, Daniunaite K., Bakavicius A., et al. Decreased expression of MT1E is a potential biomarker of prostate cancer progression. Oncotarget. 2017;8:61709. doi:10.18632/oncotarget.1868328977898
  • Fu J, Lv H, Guan H, et al. Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway. BMC Cancer. 2013;13:462. doi:10.1186/1471-2407-13-46224098937
  • Chen Y, Quan R,Bhandari A, et al. Low metallothionein 1M (MT1M) is associated with thyroid cancer cell lines progression. Am J Transl Res. 2019;11:1760.30972199
  • Appierto V. Villani MG, Cavadini, E, et al. Involvement of c-Fos in fenretinide-induced apoptosis in human ovarian carcinoma cells. Cell Death Differ. 2004;11:270–279. doi:10.1038/sj.cdd.440134914647238
  • Takekawa M, Saito H. A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell. 1998;95:521–530. doi:10.1016/S0092-8674(00)81619-09827804
  • Yoo J, Ghiassi, M, Jirmanova L., et al. Transforming grow th factor-β-induced apoptosis is mediated by Smad-dependent expression of GADD45b through p38 activation. J Biol Chem. 2003;278:43001–43007. doi:10.1074/jbc.M30786920012933797
  • Boone DN, Qi Y, Li Z, Hann SR. Egr1 mediates p53-independent c-Myc–induced apoptosis via a noncanonical ARF-dependent transcriptional mechanism. Proc Natl Acad Sci. 2011;108:632–637. doi:10.1073/pnas.100884810821187408
  • Yu J, Baron V, Mercola D, Mustelin T, Adamson ED. A network of p73, p53 and Egr1 is required for efficient apoptosis in tumor cells. Cell Death Differ. 2007;14(3):436. doi:10.1038/sj.cdd.440202916990849
  • Kim J-H, Yoon S, Won M, et al. HIP1R interacts with a member of Bcl-2 family, BCL2L10, and induces BAK-dependent cell death. Cell Physiol Biochem. 2009;23(1–3):043–52. doi:10.1159/000204088
  • Yun CW, Kim HJ, Lim JH, Lee SH. Heat shock proteins: agents of cancer development and therapeutic targets in anti-cancer therapy. Cells. 2020;9:60.
  • Chowanadisai W, Kelleher SL, Lonnerdal BO. Zinc deficiency is associated with increased brain zinc import and LIV-1 expression and decreased ZnT-1 expression in neonatal rats. J Nutr. 2005;135:1002–1007. doi:10.1093/jn/135.5.100215867272
  • Aude-Garcia C, Dalzon B, Ravanat J-L, et al. A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages. J Proteomics. 2016;134:174–185. doi:10.1016/j.jprot.2015.12.01326710724
  • García-Hevia L, Valiente R, Martín-Rodríguez R, et al. Nano-ZnO leads to tubulin macrotube assembly and actin bundling, triggering cytoskeletal catastrophe and cell necrosis. Nanoscale. 2016;8:10963–10973. doi:10.1039/C6NR00391E27228212
  • Edling CE, Hallberg B. c-Kit—a hematopoietic cell essential receptor tyrosine kinase. Int J Biochem Cell Biol. 2007;39(11):1995–1998. doi:10.1016/j.biocel.2006.12.00517350321
  • Rönnstrand L. Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci. 2004;61:2535–2548. doi:10.1007/s00018-004-4189-615526160
  • Schleussner N, Merkel O, Costanza M., et al. The AP-1-BATF and-BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma. Leukemia. 2018;32:1994–2007. doi:10.1038/s41375-018-0045-929588546
  • Logan MR, Jordan-Williams KL, Poston S, Liao J, Taparowsky EJ. Overexpression of Batf induces an apoptotic defect and an associated lymphoproliferative disorder in mice. Cell Death Dis. 2012;3:e310–e10. doi:10.1038/cddis.2012.4922592317
  • Shivtiel S, Lapid K, Kalchenko V, et al. CD45 regulates homing and engraftment of immature normal and leukemic human cells in transplanted immunodeficient mice. Exp Hematol. 2011;39(1161–70):e1.
  • Ma Y. Han, C.-C.; Huang, Q.; Sun, W.-Y. and Wei, W. GRK2 overexpression inhibits IGF1-induced proliferation and migration of human hepatocellular carcinoma cells by downregulating EGR1. Oncol Rep. 2016;35:3068–3074. doi:10.3892/or.2016.464126936374
  • Tagoug I, De Chalon AS, Dumontet C. Inhibition of IGF-1 signalling enhances the apoptotic effect of AS602868, an IKK2 inhibitor, in multiple myeloma cell lines. PLoS One. 2011;6.
  • Strömberg T, Ekman S, Girnita L, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells. Blood. 2006;107:669–678. doi:10.1182/blood-2005-01-030616166596
  • Park H, Chan, MM and Iritani, BM. Hem-1: putting the “WAVE” into actin polymerization during an immune response. FEBS Lett. 2010;584:4923–4932.20969869
  • Joshi AD, Hegde GV, Dickinson JD, et al. ATM, CTLA4, MNDA, and HEM1 in High versus Low CD38–Expressing B-cell chronic lymphocytic leukemia. Clin Cancer Res. 2007;13:5295–5304. doi:10.1158/1078-0432.CCR-07-028317875758
  • Cao L, Branstrom A, Baird J, et al. PTC299 is a novel DHODH inhibitor that modulates VEGFA mRNA translation and inhibits proliferation of a broad range of leukemia cells. Blood. 2017;130:1371.
  • Ghosh A, Dasgupta D, Ghosh A, et al. MiRNA199a-3p suppresses tumor growth, migration, invasion and angiogenesis in hepatocellular carcinoma by targeting VEGFA, VEGFR1, VEGFR2, HGF and MMP2. Cell Death Dis. 2017;8(3):e2706–e06. doi:10.1038/cddis.2017.12328358369
  • Moser B, Wolf M, Walz A,et al. Chemokines: multiple levels of leukocyte migration control. Trends Immunol 2004;25:75–84.
  • Mukaida N. Tanabe, Y. and Baba, T. Chemokines as a conductor of bone marrow microenvironment in chronic myeloid leukemia. Int J Mol Sci. 2017;18:1824. doi:10.3390/ijms18081824
  • Olsnes AM, Hatfield KJ, Bruserud Ø. The chemokine system and its contribution to leukemogenesis and treatment responsiveness in patients with acute myeloid leukemia. J BUON. 2009;14:S131–40.19785055
  • Burger J A. Chemokines and chemokine receptors in chronic lymphocytic leukemia (CLL): from understanding the basics towards therapeutic targeting. Seminars in cancer biology 2010;20:424–430.
  • Vainchenker W, Constantinescu SN. JAK/STAT signaling in hematological malignancies. Oncogene. 2013;32:2601–2613.22869151
  • Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA. JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia. 2004;18:189–218.14737178
  • Faderl S, Ferrajoli A, Harris D, et al. Atiprimod blocks phosphorylation of JAK-STAT and inhibits proliferation of acute myeloid leukemia (AML) cells. Leuk Res. 2007;31:91–95. doi:10.1016/j.leukres.2006.05.02716828865
  • Hayakawa F, Sugimoto K, Harada Y, et al. A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases. Blood Cancer J. 2013;3:e166–e66. doi:10.1038/bcj.2013.6324292418
  • Zhao S, Konopleva M, Cabreira-Hansen M, et al. Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias. Leukemia 2004;18:267–275.
  • Barragán M, Bellosillo B, Campas C, et al. Involvement of protein kinase C and phosphatidylinositol 3–kinase pathways in the survival of B-cell chronic lymphocytic leukemia cells. Blood J Am Soc Hematol. 2002;99:2969–2976.
  • Herman SEM, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood J Am Soc Hematol. 2010;116:2078–2088.
  • Ashrafizadeh M, Ahmadi Z, Kotla NG, et al. Nanoparticles targeting STATs in cancer therapy. Cells. 2019;8:1158. doi:10.3390/cells8101158
  • Matarrese P, Fusco O, Tinari N, et al. Galectin‐3 overexpression protects from apoptosis by improving cell adhesion properties. Int J Cancer. 2000;85:545–554. doi:10.1002/(SICI)1097-0215(20000215)85:4<545::AID-IJC17>3.0.CO;2-N10699929
  • Okada K. Hirota E, Mizutani Y, et al. Oncogenic role of NALP7 in testicular seminomas. Cancer Sci. 2004;95:949–954. doi:10.1111/j.1349-7006.2004.tb03182.x15596043
  • Zeng C, Li X, Li A, et al. Knockdown of NUPR1 inhibits the growth of U266 and RPMI8226 multiple myeloma cell lines via activating PTEN and caspase activation‑dependent apoptosis. Oncol Rep. 2018;40:1487–1494.30015974
  • An S, Zheng, Y. and Bleu, T. Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. J Biol Chem. 2000;275:288–296. doi:10.1074/jbc.275.1.28810617617
  • Nogueira DR, Rolim CMB, Farooqi AA. Nanoparticle induced oxidative stress in cancer cells: adding new pieces to an incomplete jigsaw puzzle. Asian Pac J Cancer Prev. 2014;15:4739–4743. doi:10.7314/APJCP.2014.15.12.473924998535
  • Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 2002;33:337–349. doi:10.1016/S0891-5849(02)00905-X12126755
  • Gelain DP, Dalmolin RJS, Belau VL, Moreira JCF, Klamt F, Castro MA. A systematic review of human antioxidant genes. Front Biosci. 2009;14:4457–4463. doi:10.2741/3541
  • Muthuraman P, Ramkumar K, Kim DH. Analysis of dose-dependent effect of zinc oxide nanoparticles on the oxidative stress and antioxidant enzyme activity in adipocytes. Appl Biochem Biotechnol. 2014;174:2851–2863. doi:10.1007/s12010-014-1231-525234395
  • Syama S, Reshma SC, Sreekanth PJ, Varma HK, Mohanan P. V. Effect of zinc oxide nanoparticles on cellular oxidative stress and antioxidant defense mechanisms in mouse liver. Toxicol Environ Chem. 2013;95:495–503. doi:10.1080/02772248.2013.789606
  • MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999;366:82–88. doi:10.1006/abbi.1999.120210334867
  • Folz RJ, Crapo JD. Extracellular superoxide dismutase (SOD3): tissue-specific expression, genomic characterization, and computer-assisted sequence analysis of the human EC SOD gene. Genomics. 1994;22:162–171. doi:10.1006/geno.1994.13577959763
  • Jaramillo-Gutierrez G, Molina-Cruz A, Kumar S, Barillas-Mury C. The Anopheles gambiae oxidation resistance 1 (OXR1) gene regulates expression of enzymes that detoxify reactive oxygen species. PLoS One. 2010;5.
  • Wang X, Wang L, Wang XE, Sun F, WangC-C. Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4. Biochem J. 2012;441:113–118. doi:10.1042/BJ2011038021916849
  • Arthur JR. The glutathione peroxidases. Cell Mol Life Sci. 2001;57:1825–1835. doi:10.1007/PL00000664
  • Hanschmann E-M, Godoy JR, Berndt C, Hudemann C, Lillig CH. Thioredoxins, glutaredoxins, and peroxiredoxins—molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid Redox Signal. 2013;19:1539–1605. doi:10.1089/ars.2012.459923397885
  • Liu H, Lu Z-G, Miki Y, Yoshida K. Protein kinase C δ induces transcription of the TP53 tumor suppressor gene by controlling death-promoting factor Btf in the apoptotic response to DNA damage. Mol Cell Biol. 2007;27:8480–8491. doi:10.1128/MCB.01126-0717938203
  • Lee JH, Kang Y, Khare V, et al. The p53-inducible gene 3 (PIG3) contributes to early cellular response to DNA damage. Oncogene. 2010;29:1431–1450. doi:10.1038/onc.2009.43820023697
  • Lugovskoy AA, Zhou P, Chou JJ, McCarty JS, Li P, Wagner G. Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis. Cell. 1999;99:747–755. doi:10.1016/S0092-8674(00)81672-410619428
  • Liang L, Zhao, M, Xu Z, Yokoyama KK, Li T. Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family. Biochem J. 2003;370:195–203. doi:10.1042/bj2002065612429024
  • Iglesias-Guimarais V, Gil-Guiñon E, Gabernet G, et al. Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease. J Biol Chem. 2012;287:7766–7779. doi:10.1074/jbc.M111.29071822253444
  • Huang DCS, Strasser A. BH3-only proteins—essential initiators of apoptotic cell death. Cell. 2000;103:839–842. doi:10.1016/S0092-8674(00)00187-211136969
  • Xue L, Chu F, Cheng Y, et al. Siva-1 binds to and inhibits BCL-XL-mediated protection against UV radiation-induced apoptosis. Proc Natl Acad Sci. 2002;99:6925–6930. doi:10.1073/pnas.10218229912011449
  • Vogler M. BCL2A1: the underdog in the BCL2 family. Cell Death Differ. 2012;19:67–74. doi:10.1038/cdd.2011.15822075983
  • He M-X, He Y-W. c-FLIP protects T lymphocytes from apoptosis in the intrinsic pathway. J Immunol. 2015;194:3444–3451. doi:10.4049/jimmunol.140046925725104
  • Deveraux QL, Reed JC. IAP family proteins—suppressors of apoptosis. Genes Dev. 1999;13:239–252. doi:10.1101/gad.13.3.2399990849
  • Chau BN, Cheng EHY, Kerr DA, Hardwick JM. Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1. Mol Cell. 2000;6:31–40. doi:10.1016/S1097-2765(05)00021-310949025
  • Chen L, Willis, SN, Wei A, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell. 2005;17:393–403. doi:10.1016/j.molcel.2004.12.03015694340
  • Borrelli A, Schiattarella A, Mancini R, et al. A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells. Free Radic Biol Med. 2009;46:110–116. doi:10.1016/j.freeradbiomed.2008.10.03018996183
  • Chen P-M, Cheng Y-W, Wu T-C, Chen C-Y, Lee H. MnSOD overexpression confers cisplatin resistance in lung adenocarcinoma via the NF-κB/Snail/Bcl-2 pathway. Free Radic Biol Med. 2015;79:127–137. doi:10.1016/j.freeradbiomed.2014.12.00125499851
  • Nagata S. Fas ligand-induced apoptosis. Annu Rev Genet. 1999;33:29–55. doi:10.1146/annurev.genet.33.1.2910690403
  • Hsu H, Huang J, Shu H-B, Baichwal V, Goeddel DV. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity. 1996;4:387–396. doi:10.1016/S1074-7613(00)80252-68612133
  • Walczak H, Degli‐Esposti MA, Johnson RS, et al. TRAIL‐R2: a novel apoptosis‐mediating receptor for TRAIL. EMBO J. 1997;16:5386–5397. doi:10.1093/emboj/16.17.53869311998
  • Salvesen GS. Caspase 8: igniting the death machine. Structure. 1999;7:R225–R29. doi:10.1016/S0969-2126(00)80048-910545333
  • Gilmore TD. Introduction to NF-κB: players, pathways, perspectives. Oncogene. 2006;25(51):6680–6684. doi:10.1038/sj.onc.120995417072321
  • Reber L, Vermeulen L, Haegeman G, Frossard N. Ser276 phosphorylation of NF-kB p65 by MSK1 controls SCF expression in inflammation. PLoS One. 2009;4:e4393. doi:10.1371/journal.pone.000439319197368
  • Bandapalli OR, Ehrmann F, Ehemann V, et al. Down-regulation of CXCL1 inhibits tumor growth in colorectal liver metastasis. Cytokine. 2012;57:46–53. doi:10.1016/j.cyto.2011.10.01922129625
  • Liu J-Y, Zeng Q-H, Cao P-G, et al. RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway. Br J Cancer. 2018;118:1617–1627.29867225
  • Hamidi T, Algül H, Cano CE, et al. Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis. J Clin Invest. 2012;122:2092–2103. doi:10.1172/JCI6014422565310
  • You Z, Ouyang H, Lopatin D, Polver PJ, WangC-Y. Nuclear factor-κB-inducible death effector domain-containing protein suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8 activity. J Biol Chem. 2001;276:26398–26404. doi:10.1074/jbc.M10246420011346652
  • Gyrd-Hansen M, Meier P. IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer. Nat Rev Cancer. 2010;10:561–574.20651737
  • Matsuda A, Suzuki Y, Honda G, et al. Large-scale identification and characterization of human genes that activate NF-κ B and Mapk signaling pathways. Oncogene. 2003;22:3307–3318. doi:10.1038/sj.onc.120640612761501