Skip to main content
Have a personal or library account? Click to login
The Effect of Metamizole on Viability and Oxidative Stress in the C6 Rat Glioma Cell Line Cover

The Effect of Metamizole on Viability and Oxidative Stress in the C6 Rat Glioma Cell Line

Open Access
|Sep 2026

References

  1. Jasiecka A, Maślanka T, Jaroszewski JJ: Pharmacological characteristics of metamizole. Pol J Vet Sci 2014, 17(1):207-214.
  2. Pierre SC, Schmidt R, Brenneis C, Michaelis M, Geisslinger G, Scholich K: Inhibition of cyclooxygenases by dipyrone. Br J Pharmacol 2007, 151(4):494-503.
  3. Rogosch T, Sinning C, Podlewski A, Watzer B, Schlosburg J, Lichtman AH, Cascio MG, Bisogno T, Di Marzo V, Nüsing R, Imming P: Novel bioactive metabolites of dipyrone (metamizol). Bioorg Med Chem 2012, 20(1):101-107.
  4. Campos C, de Gregorio R, García-Nieto R, Gago F, Ortiz P, Alemany S: Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol 1999, 378(3):339-347.
  5. Agency EM: Metamizole-containing medicinal products: measures to minimise serious outcomes of agranulocytosis https://www.ema.europa.eu/en/news/ema-recommends-measures-minimise-serious-outcomes-known-side-effect-painkiller-metamizole2024
  6. Hayes JD, Dinkova-Kostova AT, Tew KD: Oxidative Stress in Cancer. Cancer Cell 2020, 38(2):167-197.
  7. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB: Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010, 49(11):1603-1616.
  8. Wang D, Dubois RN: Prostaglandins and cancer. Gut 2006, 55(1):115-122.
  9. Nikolova I, Marinov L, Georgieva A, Toshkova R, Malchev M, Voynikov Y, Kostadinova I: Metamizole (dipyrone) – cytotoxic and antiproliferative effects on HeLa, HT-29 and MCF-7 cancer cell lines. Biotechnol Biotechnol Equip 2018, 32(5):1327-1337.
  10. Pompeia C, Boaventura MF, Curi R: Antiapoptotic effect of dipyrone on HL-60, Jurkat and Raji cell lines submitted to UV irradiation, arachidonic acid and cycloheximide treatments. Int Immunopharmacol 2001, 1(12):2173-2182.
  11. Gomes LM, Moysés DA, Nascimento HFS, Mota TC, Bonfim LT, Cardoso PCS, Burbano RMR, Bahia MO: Genotoxic and cytotoxic effects of the drug dipyrone sodium in African green monkey kidney (Vero) cell line exposed in vitro. Naunyn Schmiedebergs Arch Pharmacol 2021, 394(7):1529-1535.
  12. Lupu GI, Pall E, Cenariu M, Nan MI, Andrei S: Effects of Metamizole, 4-Methylaminoantipyrine, and 4-Aminoantipyrine on LX-2 Liver Cell Line Viability and Apoptosis. Molecules 2024, 30(1):17.
  13. Sun Y, Huang L, Mackenzie GG, Rigas B: Oxidative stress mediates through apoptosis the anticancer effect of phospho-nonsteroidal anti-inflammatory drugs: implications for the role of oxidative stress in the action of anticancer agents. J Pharmacol Exp Ther 2011, 338(3):775-783.
  14. Rai N, Sarkar M, Raha S: Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID) causes apoptosis by ROS mediated Akt activation. Pharmacol Rep 2015, 67(6):1215-1223.
  15. Trachootham D, Alexandre J, Huang P: Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 2009, 8(7):579-591.
  16. Xin S, Huang K, Zhu XG: Non-coding RNAs: Regulators of glioma cell epithelialmesenchymal transformation. Pathol Res Pract 2019, 215(9):152539.
  17. Olivier C, Oliver L, Lalier L, Vallette FM: Drug resistance in glioblastoma: the two faces of oxidative stress. Front Mol Biosci 2020, 7:620677.
  18. Liu S, Dong L, Shi W, Zheng Z, Liu Z, Meng L, Xin Y, Jiang X: Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms. Front Pharmacol 2022, 13:921070.
  19. Nowacka A, Śniegocki M, Ziółkowska E: Oxidative Stress and antioxidants in glioblastoma: mechanisms of action, therapeutic effects and future directions. Antioxidants (Basel) 2025, 14(9):1121.
  20. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW: The 2021 WHO Classification of tumors of the central nervous system: a summary. Neuro Oncol 2021, 23(8):1231-1251.
  21. Giakoumettis D, Kritis A, Foroglou N: C6 cell line: the gold standard in glioma research. Hippokratia 2018, 22(3):105-112.
  22. Grobben B, De Deyn PP, Slegers H: Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res 2002, 310(3):257-270.
  23. Oksuz E, Atalar F, Tanırverdi G, Bilir A, Shahzadi A, Yazici Z: Therapeutic potential of cyclooxygenase-3 inhibitors in the management of glioblastoma. J Neurooncol 2016, 126(2):271-278.
  24. Malsy M, Graf B, Bundscherer A: Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1. BMC Pharmacol Toxicol 2017, 18(1):77.
  25. Bundscherer AC, Malsy M, Gruber MA, Graf BM, Sinner B: Acetaminophen and metamizole induce apoptosis in HT 29 and SW 480 colon carcinoma cell lines in vitro. Anticancer Res 2018, 38(2):745-751.
  26. Maytalman E, Nemutlu Samur D: Metamizole limits proliferation in chronic myeloid leukemia cells and triggers apoptosis via the bax/bcl-2/caspase-3 cascade. Med Oncol 2025, 42(8):288.
  27. Douša M, Jireš J: Challenges in the HPLC analysis of hydrolytically unstable compounds: Metamizole and 4-methylaminoantipyrin case study. (1873-264X (Electronic)).
  28. Rudin D, Lanzilotto A, Bachmann F, Housecroft CE, Constable EC, Drewe J, Haschke M, Krähenbühl S: Non-immunological toxicological mechanisms of metamizole-associated neutropenia in HL60 cells. Biochem Pharmacol 2019, 163:345-356.
  29. Rudin D, Schmutz M, Roos NJ, Bouitbir J, Krähenbühl S: Reactive metamizole metabolites enhance the toxicity of hemin on the ATP pool in HL60 cells by inhibition of glycolysis. Biomedicines 2020;8(7):212.
  30. Ciftel S, Suleyman B, Mammadov R, Coskun R, Coban TA, Mokhtare B, Suleyman H, Cerrah S, Cicek B, Suleyman Z: Adverse effects of metamizole on heart, lung, liver, kidney, and stomach in rats. BMC Pharmacol Toxicol 2024, 25(1):55.
  31. Deng J, Liu AD, Hou GQ, Zhang X, Ren K, Chen XZ, Li SSC, Wu YS, Cao X: N-acetylcysteine decreases malignant characteristics of glioblastoma cells by inhibiting Notch2 signaling. J Exp Clin Cancer Res 2019, 38(1):2.
  32. Noch EK, Palma L, Yim I, Bullen N, Barnett D, Walsh A, Bhinder B, Benedetti E, Krumsiek J, Gurvitch J, Khwaja S, Atlas D, Elemento O, Cantley LC: Cysteine induces mitochondrial reductive stress in glioblastoma through hydrogen peroxide production. Proc Natl Acad Sci U S A 2024, 121(8):e2317343121.
  33. Ruiz-Rodado V, Dowdy T, Lita A, Kramp T, Zhang M, Jung J, Dios-Esponera A, Zhang L, Herold-Mende CC, Camphausen K, Gilbert MR, Larion M: Cysteine is a limiting factor for glioma proliferation and survival. Mol Oncol 2022, 16(9):1777-1794.
  34. Mlejnek PA-O, Dolezel P, Kriegova EA-O, Pastvova N: N-acetylcysteine can induce massive oxidative stress, resulting in cell death with apoptotic features in human leukemia cells. LID - 10.3390/ijms222312635 [doi] LID - 12635. (1422-0067 (Electronic)).
  35. Rushworth GF, Megson IL: Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014, 141(2):150-159.
  36. Rocha CR, Garcia CC, Vieira DB, Quinet A, de Andrade-Lima LC, Munford V, Belizário JE, Menck CF: Glutathione depletion sensitizes cisplatin- and temozolomide-resistant glioma cells in vitro and in vivo. Cell Death Dis 2014, 5(10):e1505.
  37. Rocha CR, Kajitani GS, Quinet A, Fortunato RS, Menck CF: NRF2 and glutathione are key resistance mediators to temozolomide in glioma and melanoma cells. Oncotarget 2016, 7(30):48081-48092.
  38. Zhu Z, Du S, Du Y, Ren J, Ying G, Yan Z: Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis. J Neurochem 2018, 144(1):93-104.
DOI: https://doi.org/10.2478/acve-2026-0025 | Journal eISSN: 1820-7448 | Journal ISSN: 0567-8315
Language: English
Page range: 374 - 392
Submitted on: Jun 22, 2026
Accepted on: Aug 14, 2026
Published on: Sep 13, 2026
Published by: University of Belgrade, Faculty of Veterinary Medicine
In partnership with: Paradigm Publishing Services
Related subjects:

© 2026 Janko Zekovic, Zeljka Stanojevic, Jelena Tasic, Filip Radovic, Sanja Blagojevic, Aleksandra Isakovic, Sasenka Vidicevic Novakovic, published by University of Belgrade, Faculty of Veterinary Medicine
This work is licensed under the Creative Commons Attribution 4.0 License.