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Sepantronium Bromide (YM155), A Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study

  • Samaneh Reiszadeh-Jahromi
  • Mohammad-Reza Sepand
  • Samaneh Ramezani-sefidar
  • Mohsen Shahlaei
  • Sajad Moradi
  • Meysam Yazdankhah
  • Nima SanadgolEmail author
Original Paper

Abstract

Cuprizone (cup) model targets oligodendrocytes (OLGs) degeneration and is frequently used for the mechanistic understanding of de- and remyelination. Improperly, this classic model is time-consuming and the extent of brain lesions and behavioral deficits are changeable (both temporally and spatially) within a mouse strain. We aimed to offer an alternative, less time-consuming, and more reproducible cup model. Mice (C57BL/6) were treated with cup (400 mg kg−1 day−1/gavage) for three consecutive weeks to induce OLGs degeneration with or without YM155 (1 mg kg−1 day−1) to examine the effects of this molecule in cup neurotoxicity. Co-administration of cup and YM155 (cuYM) accelerated the intrinsic apoptosis of mature OLGs (MOG positive cells) through the upregulation of caspase-9 and caspase-3. In addition to the stimulation of oxidative stress via reduction of glutathione peroxidase and induction of malondialdehyde, behavioral deficits in both Open-field and Rota-rod tests were worsened by cuYM. In the cuYM group, the expression of BIRC5, BIRC4 and NAIP was reduced, but no significant changes were observed in the abundance of the other inhibitor of apoptosis proteins (cIAP1 and cIAP2) in comparison with the cup group. Moreover, in silico analysis validated that YM155 directly interrupts the binding sites of certain transcription factors, such as krüppel-like family (Klf), specificity proteins (SPs), myeloid zinc fingers (MZFs), zinc finger proteins (ZNFPs), and transcription factor activating enhancer-binding proteins (TFAPs), on the promoters of target genes. In conclusion, this modified model promotes cup-induced redox and apoptosis signaling, elevates behavioral deficits, saves time, minimizes variations, and can be employed for early evaluation of novel neuroprotective agents in oligodendropathies.

Keywords

Apoptosis Inhibitors of apoptosis proteins Multiple sclerosis Oligodendrocytes 

Notes

Acknowledgements

The authors are grateful to all respected research staffs in the Pharmaceutical Science Research Center, Tehran University of Medical Sciences, Tehran, Iran, for their help with the study.

Funding

This study was funded by University of Zabol (UOZ-GR-9517–13).

Compliance with Ethical Standards

Conflicts of interest

The authors have no conflicts of interest to declare.

Supplementary material

11064_2019_2865_MOESM1_ESM.docx (22 kb)
Supplementary file1 (DOCX 21 kb)

References

  1. 1.
    Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47(6):707–717CrossRefGoogle Scholar
  2. 2.
    Sanadgol N, Zahedani SS, Sharifzadeh M, Khalseh R, Barbari GR, Abdollahi M (2017) Recent updates in imperative natural compounds for healthy brain and nerve function: a systematic review of implications for multiple sclerosis. Curr Drug Targets 18(13):1499–1517.  https://doi.org/10.2174/1389450118666161108124414 CrossRefGoogle Scholar
  3. 3.
    Sanadgol N, Golab F, Mostafaie A, Mehdizadeh M, Abdollahi M, Sharifzadeh M, Ravan H (2016) Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines. Cell Mol Biol 62(12):24–30.  https://doi.org/10.14715/cmb/2016.62.12.5 Google Scholar
  4. 4.
    Abakumova TO, Kuz'kina AA, Zharova ME, Pozdeeva DA, Gubskii IL, Shepeleva II, Antonova OM, Nukolova NV, Kekelidze ZI, Chekhonin VP (2015) Cuprizone model as a tool for preclinical studies of the efficacy of multiple sclerosis diagnosis and therapy. Bull Exp Biol Med 159(1):111–115.  https://doi.org/10.1007/s10517-015-2903-z CrossRefGoogle Scholar
  5. 5.
    Heckers S, Held N, Kronenberg J, Skripuletz T, Bleich A, Gudi V, Stangel M (2017) Investigation of cuprizone inactivation by temperature. Neurotox Res 31(4):570–577.  https://doi.org/10.1007/s12640-017-9704-2 CrossRefGoogle Scholar
  6. 6.
    Benardais K, Kotsiari A, Skuljec J, Koutsoudaki PN, Gudi V, Singh V, Vulinovic F, Skripuletz T, Stangel M (2013) Cuprizone [bis(cyclohexylidenehydrazide)] is selectively toxic for mature oligodendrocytes. Neurotox Res 24(2):244–250.  https://doi.org/10.1007/s12640-013-9380-9 CrossRefGoogle Scholar
  7. 7.
    Oberoi-Khanuja TK, Murali A, Rajalingam K (2013) IAPs on the move: role of inhibitors of apoptosis proteins in cell migration. Cell Death Dis 4:e784.  https://doi.org/10.1038/cddis.2013.311 CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Abdel-Magid AF (2017) Modulation of the inhibitors of apoptosis proteins (IAPs) activities for cancer treatment. ACS Med Chem Lett 8(5):471–473.  https://doi.org/10.1021/acsmedchemlett.7b00148 CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Silke J, Meier P (2013) Inhibitor of apoptosis (IAP) proteins-modulators of cell death and inflammation. Cold Spring Harb Perspect Biol 1:1.  https://doi.org/10.1101/cshperspect.a008730 Google Scholar
  10. 10.
    Varughese RK, Torp SH (2016) Survivin and gliomas: a literature review. Oncol Lett 12(3):1679–1686.  https://doi.org/10.3892/ol.2016.4867 CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Xia Z, Friedlander RM (2017) Minocycline in multiple sclerosis—compelling results but too early to tell. N Engl J Med 376(22):2191–2193.  https://doi.org/10.1056/NEJMe1703230 CrossRefGoogle Scholar
  12. 12.
    Hebb AL, Moore CS, Bhan V, Campbell T, Fisk JD, Robertson HA, Thorne M, Lacasse E, Holcik M, Gillard J, Crocker SJ, Robertson GS (2008) Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination. Mult Scler 14(5):577–594.  https://doi.org/10.1177/1352458507087468 CrossRefGoogle Scholar
  13. 13.
    Cheung CH, Cheng L, Chang KY, Chen HH, Chang JY (2011) Investigations of survivin: the past, present and future. Front Biosci (Landmark Ed) 16:952–961CrossRefGoogle Scholar
  14. 14.
    Zhen W, Liu A, Lu J, Zhang W, Tattersall D, Wang J (2017) An alternative cuprizone-induced demyelination and remyelination mouse model. ASN Neuro 1:1.  https://doi.org/10.1177/1759091417725174 Google Scholar
  15. 15.
    Guo K, Huang P, Xu N, Xu P, Kaku H, Zheng S, Xu A, Matsuura E, Liu C, Kumon H (2015) A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model. Oncotarget 6(25):21137–21147.  https://doi.org/10.18632/oncotarget.4121 CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Sanadgol N, Golab F, Mostafaie A, Mehdizadeh M, Khalseh R, Mahmoudi M, Abdollahi M, Vakilzadeh G, Taghizadeh G, Sharifzadeh M (2018) Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-kappaB activation and acceleration of intrinsic myelin repair. Toxicol Appl Pharmacol 342:86–98.  https://doi.org/10.1016/j.taap.2018.01.023 CrossRefGoogle Scholar
  17. 17.
    Poorebrahim M, Asghari M, Abazari MF, Askari H, Sadeghi S, Taheri-Kafrani A, Nasr-Esfahani MH, Ghoraeian P, Aleagha MN, Arab SS, Kennedy D, Montaseri A, Mehranfar M, Sanadgol N (2018) Immunomodulatory effects of a rationally designed peptide mimetic of human IFNbeta in EAE model of multiple sclerosis. Prog Neuropsychopharmacol Biol Psychiatry 82:49–61.  https://doi.org/10.1016/j.pnpbp.2017.11.028 CrossRefGoogle Scholar
  18. 18.
    Sanadgol N, Golab F, Askari H, Moradi F, Ajdary M, Mehdizadeh M (2018) Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation. Metab Brain Dis 33(1):27–37.  https://doi.org/10.1007/s11011-017-0099-9 CrossRefGoogle Scholar
  19. 19.
    Keshavarz-Bahaghighat H, Sepand MR, Ghahremani MH, Aghsami M, Sanadgol N, Omidi A, Bodaghi-Namileh V, Sabzevari O (2018) Acetyl-L-Carnitine Attenuates Arsenic-Induced Oxidative Stress and Hippocampal Mitochondrial Dysfunction. Biol Trace Elem Res 184(2):422–435.  https://doi.org/10.1007/s12011-017-1210-0 CrossRefGoogle Scholar
  20. 20.
    Nakahara T, Kita A, Yamanaka K, Mori M, Amino N, Takeuchi M, Tominaga F, Kinoyama I, Matsuhisa A, Kudou M, Sasamata M (2011) Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. Cancer Sci 102(3):614–621.  https://doi.org/10.1111/j.1349-7006.2010.01834.x CrossRefGoogle Scholar
  21. 21.
    Shirazi MK, Azarnezhad A, Abazari MF, Poorebrahim M, Ghoraeian P, Sanadgol N, Bokharaie H, Heydari S, Abbasi A, Kabiri S, Aleagha MN, Enderami SE, Dashtaki AS, Askari H (2019) The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis. J Cell Physiol 234(7):11411–11423.  https://doi.org/10.1002/jcp.27797 CrossRefGoogle Scholar
  22. 22.
    Ranjbar A, Ghahremani MH, Sharifzadeh M, Golestani A, Ghazi-Khansari M, Baeeri M, Abdollahi M (2010) Protection by pentoxifylline of malathion-induced toxic stress and mitochondrial damage in rat brain. Hum Exp Toxicol 29(10):851–864.  https://doi.org/10.1177/0960327110363836 CrossRefGoogle Scholar
  23. 23.
    Pourkhalili N, Hosseini A, Nili-Ahmadabadi A, Hassani S, Pakzad M, Baeeri M, Mohammadirad A, Abdollahi M (2011) Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats. World J Diabetes 2(11):204–210.  https://doi.org/10.4239/wjd.v2.i11.204 CrossRefPubMedCentralGoogle Scholar
  24. 24.
    von Leden RE, Yauger YJ, Khayrullina G, Byrnes KR (2017) Central nervous system injury and nicotinamide adenine dinucleotide phosphate oxidase: oxidative stress and therapeutic targets. J Neurotrauma 34(4):755–764.  https://doi.org/10.1089/neu.2016.4486 CrossRefGoogle Scholar
  25. 25.
    Bodaghi-Namileh V, Sepand MR, Omidi A, Aghsami M, Seyednejad SA, Kasirzadeh S, Sabzevari O (2018) Acetyl-l-carnitine attenuates arsenic-induced liver injury by abrogation of mitochondrial dysfunction, inflammation, and apoptosis in rats. Environ Toxicol Pharmacol 58:11–20.  https://doi.org/10.1016/j.etap.2017.12.005 CrossRefGoogle Scholar
  26. 26.
    Mohammadi H, Karimi G, Seyed Mahdi R, Ahmad Reza D, Shafiee H, Nikfar S, Baeeri M, Sabzevari O, Abdollahi M (2011) Benefit of nanocarrier of magnetic magnesium in rat malathion-induced toxicity and cardiac failure using non-invasive monitoring of electrocardiogram and blood pressure. Toxicol Ind Health 27(5):417–429.  https://doi.org/10.1177/0748233710387634 CrossRefGoogle Scholar
  27. 27.
    Gawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT (2011) Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol 14(1):123–130.  https://doi.org/10.1017/S1461145710000805 CrossRefGoogle Scholar
  28. 28.
    Sanadgol N, Golab F, Tashakkor Z, Taki N, Moradi Kouchi S, Mostafaie A, Mehdizadeh M, Abdollahi M, Taghizadeh G, Sharifzadeh M (2017) Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis. Pharm Biol 55(1):1679–1687.  https://doi.org/10.1080/13880209.2017.1319867 CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Qian ZM, Li H, Sun H, Ho K (2002) Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev 54(4):561–587CrossRefGoogle Scholar
  30. 30.
    Lotocki G, Keane RW (2002) Inhibitors of apoptosis proteins in injury and disease. IUBMB Life 54(5):231–240.  https://doi.org/10.1080/15216540215675 CrossRefGoogle Scholar
  31. 31.
    Kita A, Mitsuoka K, Kaneko N, Nakata M, Yamanaka K, Jitsuoka M, Miyoshi S, Noda A, Mori M, Nakahara T, Sasamata M (2012) Sepantronium bromide (YM155) enhances response of human B-cell non-Hodgkin lymphoma to rituximab. J Pharmacol Exp Ther 343(1):178–183.  https://doi.org/10.1124/jpet.112.195925 CrossRefGoogle Scholar
  32. 32.
    Glaros TG, Stockwin LH, Mullendore ME, Smith B, Morrison BL, Newton DL (2012) The "survivin suppressants" NSC 80467 and YM155 induce a DNA damage response. Cancer Chemother Pharmacol 70(1):207–212.  https://doi.org/10.1007/s00280-012-1868-0 CrossRefGoogle Scholar
  33. 33.
    Kaneko N, Mitsuoka K, Amino N, Yamanaka K, Kita A, Mori M, Miyoshi S, Kuromitsu S (2014) Combination of YM155, a survivin suppressant, with bendamustine and rituximab: a new combination therapy to treat relapsed/refractory diffuse large B-cell lymphoma. Clin Cancer Res 20(7):1814–1822.  https://doi.org/10.1158/1078-0432.CCR-13-2707 CrossRefGoogle Scholar
  34. 34.
    Giaccone G, Zatloukal P, Roubec J, Floor K, Musil J, Kuta M, van Klaveren RJ, Chaudhary S, Gunther A, Shamsili S (2009) Multicenter phase II trial of YM155, a small-molecule suppressor of survivin, in patients with advanced, refractory, non-small-cell lung cancer. J Clin Oncol 27(27):4481–4486.  https://doi.org/10.1200/JCO.2008.21.1862 CrossRefGoogle Scholar
  35. 35.
    Lewis KD, Samlowski W, Ward J, Catlett J, Cranmer L, Kirkwood J, Lawson D, Whitman E, Gonzalez R (2011) A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma. Invest New Drugs 29(1):161–166.  https://doi.org/10.1007/s10637-009-9333-6 CrossRefGoogle Scholar
  36. 36.
    Papadopoulos KP, Lopez-Jimenez J, Smith SE, Steinberg J, Keating A, Sasse C, Jie F, Thyss A (2016) A multicenter phase II study of sepantronium bromide (YM155) plus rituximab in patients with relapsed aggressive B-cell Non-Hodgkin lymphoma. Leuk Lymphoma 57(8):1848–1855.  https://doi.org/10.3109/10428194.2015.1113275 CrossRefGoogle Scholar
  37. 37.
    Satoh T, Okamoto I, Miyazaki M, Morinaga R, Tsuya A, Hasegawa Y, Terashima M, Ueda S, Fukuoka M, Ariyoshi Y, Saito T, Masuda N, Watanabe H, Taguchi T, Kakihara T, Aoyama Y, Hashimoto Y, Nakagawa K (2009) Phase I study of YM155, a novel survivin suppressant, in patients with advanced solid tumors. Clin Cancer Res 15(11):3872–3880.  https://doi.org/10.1158/1078-0432.CCR-08-1946 CrossRefGoogle Scholar
  38. 38.
    Tolcher AW, Mita A, Lewis LD, Garrett CR, Till E, Daud AI, Patnaik A, Papadopoulos K, Takimoto C, Bartels P, Keating A, Antonia S (2008) Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of survivin. J Clin Oncol 26(32):5198–5203.  https://doi.org/10.1200/JCO.2008.17.2064 CrossRefPubMedCentralGoogle Scholar
  39. 39.
    Steelman AJ, Zhou Y, Koito H, Kim S, Payne HR, Lu QR, Li J (2016) Activation of oligodendroglial Stat3 is required for efficient remyelination. Neurobiol Dis 91:336–346.  https://doi.org/10.1016/j.nbd.2016.03.023 CrossRefPubMedCentralGoogle Scholar
  40. 40.
    Cheng Q, Ling X, Haller A, Nakahara T, Yamanaka K, Kita A, Koutoku H, Takeuchi M, Brattain MG, Li F (2012) Suppression of survivin promoter activity by YM155 involves disruption of Sp1-DNA interaction in the survivin core promoter. Int J Biochem Mol Biol 3(2):179–197PubMedCentralGoogle Scholar
  41. 41.
    Nakamura N, Yamauchi T, Hiramoto M, Yuri M, Naito M, Takeuchi M, Yamanaka K, Kita A, Nakahara T, Kinoyama I, Matsuhisa A, Kaneko N, Koutoku H, Sasamata M, Yokota H, Kawabata S (2012) Furuichi K (2012) Interleukin enhancer-binding factor 3/NF110 is a target of YM155, a suppressant of survivin. Mol Cell Proteomics 1:1.  https://doi.org/10.1074/mcp.M111.013243 Google Scholar
  42. 42.
    Ho SH, Ali A, Chin TM, Go ML (2016) Dioxonaphthoimidazoliums AB1 and YM155 disrupt phosphorylation of p50 in the NF-κB pathway. Oncotarget 7(10):11625–11636CrossRefPubMedCentralGoogle Scholar
  43. 43.
    Yamauchi T, Nakamura N, Hiramoto M, Yuri M, Yokota H, Naitou M, Takeuchi M, Yamanaka K, Kita A, Nakahara T, Kinoyama I, Matsuhisa A, Kaneko N, Koutoku H, Sasamata M, Kobori M, Katou M, Tawara S, Kawabata S, Furuichi K (2012) Sepantronium bromide (YM155) induces disruption of the ILF3/p54(nrb) complex, which is required for survivin expression. Biochem Biophys Res Commun 425(4):711–716.  https://doi.org/10.1016/j.bbrc.2012.07.103 CrossRefGoogle Scholar
  44. 44.
    Goldberg J, Clarner T, Beyer C, Kipp M (2015) Anatomical Distribution of Cuprizone-Induced Lesions in C57BL6 Mice. J Mol Neurosci 57(2):166–175.  https://doi.org/10.1007/s12031-015-0595-5 CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of BiologyUniversity of Sistan and BaluchestanZahedanIran
  2. 2.Department of Toxicology and Pharmacology, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  3. 3.Department of Biology, Faculty of Basic SciencesRazi UniversityKermanshahIran
  4. 4.Nano Drug Delivery Research Center, School of PharmacyKermanshah University of Medical ScienceKermanshahIran
  5. 5.Department of OphthalmologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  6. 6.Department of Biology, Faculty of SciencesUniversity of ZabolZabolIran

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