Skip to main content

Advertisement

SpringerLink
Log in

Adriamycin induces myocardium apoptosis through activation of nuclear factor κB in rat

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Adriamycin is one of the most effective and useful antineoplastic agents. Acute doxorubicin cardiotoxicity involved cardiomyocyte apoptosis. In this study, we investigated whether adriamycin induced myocardium apoptosis through activation of nuclear factor κB in rat. Forty male Wistar rats were randomly divided into five groups: control, ADR 5 mg/kg, ADR 10 mg/kg, ADR 15 mg/kg group and ADR + PDTC 200 mg/ml group. Myocardial apoptosis was detected by DNA fragmentation assay and TUNEL assay; Location and distribution of p-IκBα was observed by immunohistochemical assay; Myocardial expression of p-IκBα protein was assessed by Western blot analysis; Activity of NF-κB was evaluated by Electrophoretic Mobility Shift Assay. The myocardial apoptotic index, expression of p-IκBα, and binding activity of NF-κB increased significantly in ADR groups in dose-dependent manner. PDTC as a nonspecific inhibitor of NF-κB protected myocardium from apoptosis by inhibiting NF-κB activation. Adriamycin induces myocardium apoptosis through activation of nuclear factor κB in rat and NF-κB activation requires IκBα degradation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Morabito A, Gattuso D, Stani SC (2004) Safety and activity of the combination of pegylated liposomal Doxorubicin and weekly docetaxel in advanced breast cancer. Breast Cancer Res Treat 86:249–257

    Article  PubMed  CAS  Google Scholar 

  2. Novitzky N, Thomas V, Abrahams L, Toit C, Donald M (2004) Increasing dose intensity of anthracycline antibiotics improves outcome in patients with acute myelogenous leukemia. Am J Hematol 76:319–329

    Article  PubMed  CAS  Google Scholar 

  3. Hequet O, Le QH, Moullet I (2004) Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults. J Clin Oncol 22:1864–1871

    Article  PubMed  CAS  Google Scholar 

  4. Lipshultz SE, Rifai N, Dalton VM (2004) The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 351:145–153

    Article  PubMed  CAS  Google Scholar 

  5. Olli JA, Antti S, Kari P, Markku K, Martti P, Liisa-Maria V-P (2000) Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res 60:1789–1792

    Google Scholar 

  6. Nakamura T, Ueda Y, Juan Y, Katsuda S, Takahashi H, Koh E (2000) Fas-mediated apoptosis in adriamycin-induced cardiomyopathy in rats: in vivo study. Circulation 102:572–578

    PubMed  CAS  Google Scholar 

  7. Lou H, Danelisen I, Singal PK (2005) Involvement of mitogen-activated protein kinases in adriamycin-induced cardiomyopathy. Am J Physiol Heart Circ Physiol 288:H1925–H1930

    Article  PubMed  CAS  Google Scholar 

  8. Muller DN, Dechend R, Mervaala E (2000) NF-κB inhibition ameliorates angiotensin II-induced inflammatory damage in rats. Hypertension 35:193–201

    PubMed  CAS  Google Scholar 

  9. Beswick RA, Zhang H, Marable D, Catravas JD, Hill WD, Webb RC (2001) Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response. Hypertension 37:781–786

    PubMed  CAS  Google Scholar 

  10. Kim SB, Kim JS, Lee JH, Yoon WJ, Lee DS, Ko MS, Kwon BS, Choi DH, Cho HR, Lee BJ, Chung DK, Lee HW, Park JW (2006) NF-κB activation is required for cisplatin-induced apoptosis in head and neck squamous carcinoma cells. FEBS Lett 580:311–318

    Article  PubMed  CAS  Google Scholar 

  11. Chong ZZ, Li F, Maiese K (2005) Erythropoietin requires NF-κB and its nuclear translocation to prevent early and late apoptotic neuronal injury during beta-amyloid toxicity. Curr Neurovasc Res 2:387–399

    Article  PubMed  CAS  Google Scholar 

  12. Zhou S, Palmeira CM, Wallace KB (2001) Doxorubicin-induced persistent oxidative stress to cardiac myocytes. Toxicol Lett 121:151–157

    Article  PubMed  CAS  Google Scholar 

  13. Koutinos G, Stathopoulos GP, Dontas I (2002) The effect of doxorubicin and its analogue mitoxantrone on cardiac muscle and on serum lipids: an experimental study. Anticancer Res 22:815–820

    PubMed  CAS  Google Scholar 

  14. Mukherjee S, Banerjee SK, Maulik M, Dinda AK, Talwar KK, Maulik SK (2003) Protection against acute adriamycin-induced cardiotoxicity by garlic: role of endogenous antioxidants and inhibition of TNF-α expression. BMC Pharmacol 3:16

    Article  PubMed  Google Scholar 

  15. Mohamed HE, Asker ME, Ali SI, Fattah TM (2004) Protection against doxorubicin cardiomyopathy in rats: role of phosphodiesterase inhibitors type 4. Pharm Pharmacol 56:757–768

    CAS  Google Scholar 

  16. Dudnakova TV, Lakomkin VL, Tsyplenkova VG, Shekhonin BV, Shirinsky VP, Kapelko VI (2003). Alterations in myocardial cytoskeletal and regulatory protein expression following a single Doxorubicin injection. J Cardiovasc Pharmacol 41:788–794

    Article  PubMed  CAS  Google Scholar 

  17. RVitelli M, Filippelli A, Rinaldi B (2002) Effects of docosahexaenoic acid on [Ca(2+)](i) increase induced by doxorubicin in ventricular rat cardiomyocytes. Life Sci 71:1905–1916

    Article  PubMed  CAS  Google Scholar 

  18. Zhou S, Heller LJ, Wallace KB (2001) Interference with calcium-dependent mitochondrial bioenergetics in cardiac myocytes isolated from doxorubicin-treated rats. Toxicol Appl Pharmacol 175:60–67

    Article  PubMed  CAS  Google Scholar 

  19. Wu S, Ko YS, Teng MS (2002) Adriamycin-induced cardiomyocyte and endothelial cell apoptosis: in vitro and in vivo studies. J Mol Cell Cardiol 34:1595–1607

    Article  PubMed  CAS  Google Scholar 

  20. Zhao W, Lu L, Chen SS, Sun Y (2004) Temporal and spatial characteristics of apoptosis in the infarcted rat heart. Biochem Biophys Res Commun 325:605–611

    Article  PubMed  CAS  Google Scholar 

  21. Somerville L, Cory JG (2000) Enhanced roscovitine-induced apoptosis is mediated by a caspase-3-like activity in deoxyadenosine-resistant mouse leukemia L1210 cells. Anticancer Res 20:3347–3355

    PubMed  CAS  Google Scholar 

  22. Jimi E, Nakamura I, Ikebe T, Akiyama S, Takahashi N, Suda T (1998) Activation of NF-κB is involved in the survival of osteoclasts promoted by interleukin-1. J Biol Chem 273:8799–8805

    Article  PubMed  CAS  Google Scholar 

  23. Bakker TR, Reed D, Renno T, Jongeneel CV (1999) Efficient adenoviral transfer of NF-κB inhibitor sensitizes melanoma to tumor necrosis factor-mediated apoptosis. Int J Cancer 80:320–323

    Article  PubMed  CAS  Google Scholar 

  24. Arlt A, Vorndamm J, Breitenbroich M, Folsch UR, Kalthoff H, Schmidt WE, Schafer H (2001) Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin. Oncogene 20:859–868

    Article  PubMed  CAS  Google Scholar 

  25. Sumitomo M, Tachibana M, Ozu C, Asakura H, Murai M, Hayakawa M, Nakamura H, Takayanagi A, Shimizu N (1999) Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression. Hum Gene Ther 10:37–47

    Article  PubMed  CAS  Google Scholar 

  26. Sovak MA, Bellas RE, Kim DW, Zanieski GJ, Rogers AE, Traish AM, Sonenshein GE (1997) Aberrant nuclear factor-κB/Rel expression and the pathogenesis of breast cancer. J Clin Invest 100:2952–2960

    Article  PubMed  CAS  Google Scholar 

  27. Higuchi Y, Otsu K, Nishida K, Hirotani S, Nakayama H, Yamaguchi O, Matsumura Y, Ueno H, Tada M, Hori M (2002) Involvement of reactive oxygen species-mediated NF-κB activation in TNF-alpha-induced cardiomyocyte hypertrophy. J Mol Cell Cardiol 34:233–240

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Second Affiliated Hospital of Harbin medical University, 246 Xuefu Road, Harbin, 150086, PR China

    Shufeng Li & Bo Yu

  2. Department of Radiotherapy, Harbin Medical University Affiliated Tumor Hospital, Harbin, 150086, PR China

    Mingyan E

Authors
  1. Shufeng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingyan E
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bo Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, S., E, M. & Yu, B. Adriamycin induces myocardium apoptosis through activation of nuclear factor κB in rat. Mol Biol Rep 35, 489–494 (2008). https://doi.org/10.1007/s11033-007-9112-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-007-9112-4

Keywords

Search

Navigation