Ukr.Biochem.J. 2018; Том 90, № 2, березень-квітень, c. 46-54

doi: https://doi.org/10.15407/ubj90.02.046

Impact of N-acetylcysteine on antitumor activity of doxorubicin and landomycin A in NK/Ly lymphoma-bearing mice

Yu. S. Kozak1, R. R. Panchuk2, N. R. Skorokhyd2, L. V. Lehka2, R. S. Stoika1,2

 1Ivan Franko National University of Lviv, Ukraine;
2Іnstitute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
e-mail: stoika@cellbiol.lviv.ua

N-acetylcysteine (NAC) is a dietary supplement demonstrating antioxidant and liver protecting effects that is widely used in clinics. NAC is considered to possess potential therapeutic activity for health disorders characterized by generation of free oxygen radicals, as well as potential for decreasing negative side effects of various drugs. However, the mechanisms of such tissue-protective actions of NAC remain poorly understood. The main aim of this work was to study therapeutic effects of NAC applied together with the “gold standard” of chemotherapy doxorubicin (Dx) or the novel experimental drug landomycin A (LA) to mice bearing NK/Ly lymphoma. It was revealed that NAC significantly decreased the nephrotoxicity of Dx (measured as creatinine level), possessed moderate immunomodulating activity (as revealed by an increase in number of cytotoxic T-lymphocytes), and partially increased survival of NK/Ly lymphoma-bearing animals treated with Dx. On the contrary, there was little tissue-protective effect of NAC towards LA due to the weak side effects of this anticancer drug, however, the combined use of NAC and LA significantly increased survival (60+ days) of LA-treated animals with NK/Ly lymphoma. Summarizing, NAC possesses a moderate tissue-protective activity towards Dx action but lacks a major therapeutic effect. However, in the case of LA action, NAC significantly increases its anticancer activity with no impact on its negative side effects. Further studies of the molecular mechanisms underlying that activity of NAC towards the action of LA are in progress.

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Посилання:

  1. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004 Oct 2-8;364(9441):1219-28. PubMed,CrossRef
  2. Group ACPS. The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Ann Epidemiol. 1994 Jan;4(1):1-10. PubMed,CrossRef
  3. Panchuk RR, Skorokhyd NR, Kozak YS, Lehka LV, Moiseenok AG, Stoika RS. Tissue-protective activity of selenomethionine and D-panthetine in B16 melanoma-bearing mice under doxorubicin treatment is not connected with their ROS scavenging potential. Croat Med J. 2017 Apr 14;58(2):171-184. PubMed, PubMedCentral, CrossRef
  4. Panchuk RR, Skorokhyd NR, Kozak YS, Lehka LV, Chumak VV, Omelyanchik SN, Gurinovich VA, Moiseenok AG, Stoika RS. Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice. Croat Med J. 2016 Apr 23;57(2):180-92. PubMed, PubMedCentral, CrossRef
  5. Poole PJ, Black PN. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. BMJ. 2001 May 26;322(7297):1271-4. PubMed, PubMedCentral,CrossRef
  6. Wang N, Qian P, Kumar S, Yan TD, Phan K. The effect of N-acetylcysteine on the incidence of contrast-induced kidney injury: A systematic review and trial sequential analysis. Int J Cardiol. 2016 Apr 15;209:319-27.  PubMed, CrossRef
  7. Aitio ML. N-acetylcysteine – passe-partout or much ado about nothing? Br J Clin Pharmacol. 2006 Jan;61(1):5-15. PubMed, PubMedCentral, CrossRef
  8. Green JL, Heard KJ, Reynolds KM, Albert D. Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis. West J Emerg Med. 2013 May;14(3):218-26. PubMed, PubMedCentral, CrossRef
  9. Palma PC, Villaça Júnior CJ, Netto Júnior NR. N-acetylcysteine in the prevention of cyclophosphamide induced haemorrhagic cystitis. Int Surg. 1986 Jan-Mar;71(1):36-7. PubMed
  10. Villani F, Galimberti M, Monti E, Piccinini F, Lanza E, Rozza A, Favalli L, Poggi P, Zunino F. Effect of glutathione and N-acetylcysteine on in vitro and in vivo cardiac toxicity of doxorubicin. Free Radic Res Commun. 1990;11(1-3):145-51. PubMed, CrossRef
  11. Morini M, Cai T, Aluigi MG, Noonan DM, Masiello L, De Flora S, D’Agostini F, Albini A, Fassina G. The role of the thiol N-acetylcysteine in the prevention of tumor invasion and angiogenesis. Int J Biol Markers. 1999 Oct-Dec;14(4):268-71. PubMed, CrossRef
  12. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004 Jun;56(2):185-229. PubMed, CrossRef
  13. Panchuk RR, Lehka LV, Terenzi A, Matselyukh BP, Rohr J, Jha AK, Downey T, Kril IJ, Herbacek I, van Schoonhoven S, Heffeter P, Stoika RS, Berger W. Rapid generation of hydrogen peroxide contributes to the complex cell death induction by the angucycline antibiotic landomycin E. Free Radic Biol Med. 2017 May;106:134-147. PubMed, PubMedCentral, CrossRef
  14. Ronin VS, Starobinets GM, Utevsky NL. Textbook for classes on the methods of clinical laboratory investigations. 4th ed. Moscow: Medicine; 1989. 335 p.
  15. Wilkinson K, Fikes J, Wojcik S. Improved mouse blood smears using the DiffSpin slide spinner. Vet Clin Pathol. 2001;30(4):197-200. PubMed
  16. Roscoe MH. The estimation of creatinine in serum. J Clin Pathol. 1953 Aug;6(3):201-7. PubMed, PubMedCentralCrossRef
  17. Panchuk RR, Boiko NM, Lootsik MD, Stoika RS. Changes in cytokine production and morphology of murine lymphoma NK/Ly cells in course of tumor development. Cent Eur J Biol. 2007;2(1):71.  CrossRef
  18. Panchuk RR, Boiko NM, Lootsik MD, Stoika RS. Changes in signaling pathways of cell proliferation and apoptosis during NK/Ly lymphoma aging. Cell Biol Int. 2008 Sep;32(9):1057-63. PubMed, CrossRef
  19. Zombeck JA, Fey EG, Lyng GD, Sonis ST. A clinically translatable mouse model for chemotherapy-related fatigue. Comp Med. 2013;63(6):491-7. PubMed, PubMedCentral
  20. Porporato PE. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis. 2016 Feb 22;5:e200.  PubMed, PubMed, CrossRef
  21. Lahoti TS, Patel D, Thekkemadom V, Beckett R, Ray SD. Doxorubicin-induced in vivo nephrotoxicity involves oxidative stress-mediated multiple pro- and anti-apoptotic signaling pathways. Curr Neurovasc Res. 2012 Nov;9(4):282-95. PubMed, CrossRef

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