Protective Role of Curcumin on Apoptosis Levels in Sodium Azide-Induced Stress Model in SH-SY5Y Cells
DOI:
https://doi.org/10.66588/NCMR.3.2.04Keywords:
Sodium azide, Curcumin, Mitochondria, SH-SY5Y cellsAbstract
Oxidative stress, impairments of cellular ATP production and changes in membrane integrity of mitochondria are components of mitochondrial dysfunction and are cross borders of several neurodegenerative diseases. Sodium azide is a chemical agent targeting mitochondrial oxidative phosphorylation and widely used in experimental stress models and hypoxia in neuronal cells. Therefore, in this study it was aimed to investigate the possible role of curcumin on changes in molecular pathways in SH-SY5Y cells induced by SA by using different biochemical methods.
SA-gene interactions analyses were done with The Comparative Toxicogenomics Database. Pathway analysis was studied with Enrichr. Dose determination of SA was done with MTT cell viability assay and after that apoptosis, mitochondrial membrane depolarization and intracellular reactive oxygen species production assays were performed in study groups.
In this study, it has been shown that the SA model of mitochondrial stress can be decreased by curcumin treatment. Curcumin administration reverses cell death and decrease mitochondrial depolarization levels. However, it seems that curcumin may also be insufficient to decrease intracellular reactive oxygen species production. Thus, combined therapeutic approaches enhancing mitochondrial antioxidative capacity are thought to elucidate potential role of curcumin on SA-induced stress model in SH-SY5Y neuronal cells.
Downloads
References
Klemmensen MM, Borrowman SH, Pearce C, Pyles B, Chandra B. Mitochondrial dysfunction in neurodegenerative disorders. Neurother J Am Soc Exp Neurother. 2024;21(1):e00292. https://doi.org/10.1016/j.neurot.2023.10.002
Vodičková A, Koren SA, Wojtovich AP. Site-specific mitochondrial dysfunction in neurodegeneration. Mitochondrion. 2022;64:1–18. https://doi.org/10.1016/j.mito.2022.02.004
Lopez-Suarez L, Awabdh S Al, Coumoul X, Chauvet C. The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants. Neurotoxicology. 2022;92:131–55. https://doi.org/10.1016/j.neuro.2022.07.008
Bennett MC, Mlady GW, Kwon Y, Rose GM. Chronic in vivo sodium azide infusion induces selective and stable inhibition of cytochrome c oxidase. J Neurochem. 1996;66(6):2606–11. https://doi.org/10.1046/j.1471-4159.1996.66062606.x
Öz A, Çelik Ö. Curcumin inhibits oxidative stress-induced TRPM2 channel activation, calcium ion entry and apoptosis values in SH-SY5Y neuroblastoma cells: Involvement of transfection procedure. Mol Membr Biol. 2016;33(3–5):76–88. https://doi.org/10.1080/09687688.2017.1318224
Sathyabhama M, Priya Dharshini LC, Karthikeyan A, Kalaiselvi S, Min T. The Credible Role of Curcumin in Oxidative Stress-Mediated Mitochondrial Dysfunction in Mammals. Biomolecules. 2022;12(10). https://doi.org/10.3390/biom12101405
Genchi G, Lauria G, Catalano A, Carocci A, Sinicropi MS. Neuroprotective Effects of Curcumin in Neurodegenerative Diseases. Foods (Basel, Switzerland). 2024;13(11). https://doi.org/10.3390/foods13111774
Armağan HH, Nazıroğlu M. Curcumin Attenuates Hypoxia-Induced Oxidative Neurotoxicity, Apoptosis, Calcium, and Zinc Ion Influxes in a Neuronal Cell Line: Involvement of TRPM2 Channel. Neurotox Res. 2021;39(3):618–33. https://doi.org/10.1007/s12640-020-00314-w
He C, Stroink A, Vogel L, Wang CX. Temperature increase exacerbates apoptotic neuronal death in chemically-induced ischemia. PLoS One. 2013;8(7):e68796. https://doi.org/10.1371/journal.pone.0068796
Çetin F, Kosba S, Abdik H, Bolat ZB. Synergistic anti-proliferative and apoptotic effect of NVP-BEZ235 and curcumin on human SH-SY5Y neuroblastoma cells. Med Oncol. 2023;41(1):11. https://doi.org/10.1007/s12032-023-02239-8
Davis AP, Wiegers TC, Sciaky D, Barkalow F, Strong M, Wyatt B, et al. Comparative Toxicogenomics Database’s 20th anniversary: update 2025. Nucleic Acids Res. 2025;53(D1):D1328–34. https://doi.org/10.1093/nar/gkae883
Xie Z, Bailey A, Kuleshov M V, Clarke DJB, Evangelista JE, Jenkins SL, et al. Gene Set Knowledge Discovery with Enrichr. Curr Protoc. 2021;1(3):e90. https://doi.org/10.1002/cpz1.90
Öz A, Çelik Ö. Downregulation of TRPM8 channels induce cell death in human DBTRG glioblastoma cells. Indian J Biochem Biophys. 2023;60(May):385–92. https://doi.org/10.56042/ijbb.v60i5.950
Öz A. Regulatory role of TRPM7 cation channels on neuronal hypoxia model. Indian J Biochem Biophys. 2023;60:836–43. https://doi.org/10.56042/ijbb.v60i11.4467
Yazğan Y, Nazıroğlu M. Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis. Mol Neurobiol. 2021;58(11):5581–601. https://doi.org/10.1007/s12035-021-02503-w
Yazıcı T, Koçer G, Nazıroğlu M, Övey İS, Öz A. Zoledronic Acid, Bevacizumab and Dexamethasone-Induced Apoptosis, Mitochondrial Oxidative Stress, and Calcium Signaling Are Decreased in Human Osteoblast-Like Cell Line by Selenium Treatment. Biol Trace Elem Res. 2018;184(2):358–68. https://doi.org/10.1007/s12011-017-1187-8
Öz A. Experimental cell culture models for investigating neurodegenerative diseases. J Cell Neurosci Oxidative Stress. 2019;11(2):835–51. https://doi.org/10.37212/jcnos.683400
Angelova PR, Abramov AY. Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett. 2018;592(5):692–702. https://doi.org/10.1002/1873-3468.12964
Tuboly E, Szabó A, Garab D, Bartha G, Janovszky Á, Ero G, et al. Methane biogenesis during sodium azide-induced chemical hypoxia in rats. Am J Physiol Cell Physiol. 2013;304(2):C207-14. https://doi.org/10.1152/ajpcell.00300.2012
Alves JL, Quinta-Ferreira RM, Quinta-Ferreira ME, Matias CM. Exploring different mechanisms of reactive oxygen species formation in hypoxic conditions at the hippocampal ca3 area. Mol Cell Endocrinol. 2025;601:112517. https://doi.org/10.1016/j.mce.2025.112517
Uǧuz AC, Öz A, Naziroǧlu M. Curcumin inhibits apoptosis by regulating intracellular calcium release, reactive oxygen species and mitochondrial depolarization levels in SH-SY5Y neuronal cells. J Recept Signal Transduct. 2016;36(4):395–401. https://doi.org/10.3109/10799893.2015.110833
Xiang B, Li D, Chen Y, Li M, Zhang Y, Sun T, et al. Curcumin Ameliorates Copper-Induced Neurotoxicity Through Inhibiting Oxidative Stress and Mitochondrial Apoptosis in SH-SY5Y Cells. Neurochem Res. 2021;46(2):367–78. https://doi.org/10.1007/s11064-020-03173-1
Yan D, Wang N, Yao J, Wu X, Yuan J, Yan H. Curcumin Attenuates the PERK-eIF2α Signaling to Relieve Acrylamide-Induced Neurotoxicity in SH SY5Y Neuroblastoma Cells. Neurochem Res. 2022;47(4):1037–48. https://doi.org/10.1007/s11064-021-03504-w
Tan B, Suluhan SN, Yaylalı O, Güneş MS, Dursun N. Curcumin protects SH-SY5Y cells against glutamate-induced excitotoxicity by maintaining genomic integrity and antioxidant balance. Drug Chem Toxicol. 2026;1–10. https://doi.org/10.1080/01480545.2026.2712041
Meyerowitz J, Parker SJ, Vella LJ, Ng DC, Price KA, Liddell JR, et al. C-Jun N-terminal kinase controls TDP-43 accumulation in stress granules induced by oxidative stress. Mol Neurodegener. 2011;6(57). https://doi.org/10.1186/1750-1326-6-57
Fitzgerald JC, Ugun-Klusek A, Allen G, De Girolamo LA, Hargreaves I, Ufer C, et al. Monoamine oxidase-A knockdown in human neuroblastoma cells reveals protection against mitochondrial toxins. FASEB J Off Publ Fed Am Soc Exp Biol. 2014;28(1):218–29. https://doi.org/10.1096/fj.13-235481
Gökçe Kütük S, Gökçe G, Kütük M, Gürses Cila HE, Nazıroğlu M. Curcumin enhances cisplatin-induced human laryngeal squamous cancer cell death through activation of TRPM2 channel and mitochondrial oxidative stress. Sci Rep. 2019;9(1):17784. https://doi.org/10.1038/s41598-019-54284-x
Wolnicka-Glubisz A, Wisniewska-Becker A. Dual Action of Curcumin as an Anti- and Pro-Oxidant from a Biophysical Perspective. Antioxidants (Basel, Switzerland). 2023;12(9). https://doi.org/10.3390/antiox12091725
Öz A, Çelik Ö, Övey İS. Effects of different doses of curcumin on apoptosis, mitochondrial oxidative stress and calcium influx in DBTRG glioblastoma cells. J Cell Neurosci Oxidative Stress. 2017;9(2):617–29. https://doi.org/10.37212/jcnos.330858
Khongrum J, Mairuae N, Thanchomnang T, Zhang M, Bai G. Synergistic Neuroprotection Through Epigenetic Modulation by Combined Curcumin-Enriched Turmeric Extract and L-Ascorbic Acid in Oxidative Stress-Induced SH-SY5Y Cell Damage. Foods. 2025;14(5):892. https://doi.org/10.3390/foods14050892
Mythri RB, Bharath MM. Curcumin: a potential neuroprotective agent in Parkinson’s disease. Curr Pharm Des. 2012;18(1):91–9. https://doi.org/10.2174/138161212798918995
Reddy PH, Manczak M, Yin X, Grady MC, Mitchell A, Tonk S, et al. Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J Alzheimer’s Dis. 2018;61(3):843–66. https://doi.org/10.3233/jad-170512
Shah R, Varghese R, Anchan H, Pai S, Zagade T, Oswal M, et al. A Decade of Mitochondria‐Targeting Drugs in Cancer Treatment: Case Review on Mitochondria‐Targeting Curcumin or Mitocurcumin. Drug Dev Res. 2025;86(8):e70188. https://doi.org/10.1002/ddr.70188
Patwardhan RS, Gohil D, Singh B, Kumar BK, Purohit V, Thoh M, et al. Mitochondrial‐targeted curcumin inhibits T‐cell activation via Nrf2 and inhibits graft‐versus‐host‐disease in a mouse model. Phyther Res. 2024;38(3):1555–73. https://doi.org/10.1002/ptr.8126

