Journals / Experimed / 2026 / Volume: 16 Issue: 1

Anti-Cancer Effects of Neocuproine via Copper Chelation in A549 Lung Adenocarcinoma Cells

Fatma Yesilyurt(ATATURK UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL PHARMACOLOGY)0000-0002-1336-6322
Ruken Avşaroğlu(ATATURK UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF PHARMACOLOGY, MEDICAL ONCOLOGY)0009-0007-6701-764X
Güven Akçay(Bolu Abant İzzet Baysal University, Faculty of Medicine, Department of Biophysics)0000-0003-3418-8825
Sena Çamur(HITIT UNIVERSITY, SCHOOL OF MEDICINE)0009-0004-2462-0244
Selma Yaman(KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOFİZİK ANABİLİM DALI)0000-0002-9301-9119
Özge Kaya(BOLU ABANT IZZET BAYSAL UNIVERSITY, FACULTY OF ARTS AND SCIENCES, BIOLOGY PR.)0000-0002-7376-3709
Sevdenur Uzun(BOLU ABANT İZZET BAYSAL ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOFİZİK ANABİLİM DALI)0009-0005-2744-1775
Ahmet Hacımüftüoğlu(ATATURK UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL PHARMACOLOGY)0000-0002-9658-3313
Journal
Experimed
Pages
—
Publication Date
2026-08-27
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Further research is needed to fully understand its effects on healthy cells and biological systems.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: Neocuproine, a dipyridyl derivative with high affinity for copper ions, was investigated for its effects on human lung adenocarcinoma A549 cells, a key model for lung cancer research.
📊
Key Findings & Data:This study evaluated neocuproine’s capacity to inhibit A549 cell proliferation and induce apoptosis, with a focus on pro-inflammatory cytokines and oxidative stress markers.
💡
Conclusion & Impact:Further research is needed to fully understand its effects on healthy cells and biological systems.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Antioxidant · A549 · Lung Cancer

Abstract

Objective: Neocuproine, a dipyridyl derivative with high affinity for copper ions, was investigated for its effects on human lung adenocarcinoma A549 cells, a key model for lung cancer research. Copper ions play crucial roles in cellular functions, such as angiogenesis and oxidative stress regulation, and their dysregulation is linked to tumor progression. This study evaluated neocuproine’s capacity to inhibit A549 cell proliferation and induce apoptosis, with a focus on pro-inflammatory cytokines and oxidative stress markers. Materials and Methods: To assess the cytotoxic effects of neocuproine, A549 cells were treated with doses ranging from 0.1 to 1000 μM. After 24 hours of incubation, cell viability was assessed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, total antioxidant status (TAS), total oxidant status (TOS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: A reduction in cell viability was observed in a concentration-dependent manner, with notable cytotoxic effects particularly evident at 10 and 100 μM doses. The IC50 of neocuproine was calculated as 31.28 μM (p<0.001). Changes in TAS, TOS, IL-6, and TNF-α levels corroborated the cytotoxicity findings from the MTT assay. Conclusion: Neocuproine effectively inhibited the growth of A549 lung cancer cells. This cytotoxic effect was particularly pronounced at doses between 10 and 100 µM, and was mediated by increasing oxidative stress and modulating inflammatory responses. These findings suggest that neocuproine is a potential therapeutic candidate for lung cancer. Further research is needed to fully understand its effects on healthy cells and biological systems.

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Cite This Article

Yesilyurt, F., Avşaroğlu, R., Akçay, G., Çamur, S., Yaman, S., Kaya, Ö., Uzun, S., Hacımüftüoğlu, A. (2026). Anti-Cancer Effects of Neocuproine via Copper Chelation in A549 Lung Adenocarcinoma Cells. Experimed, Volume: 16 Issue: 1. https://doi.org/10.26650/experimed.1720628

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References (33)

  1. Feng G, Yao H, Li C, Liu R, Huang R, Fan X, et al. ME-ACP: Multi-view neural networks with ensemble model for identification of anticancer peptides. Comput Biol Med 2022; 145: 105459. google scholar
  2. Wang S, Hu Y. alpha7 nicotinic acetylcholine receptors in lung cancer. Oncol Lett 2018; 16(2): 1375-82. google scholar
  3. Xue L, Liu J, Xie J, Luo J. Prognostic value of SLC16A3(MCT4) in lung adenocarcinoma and its clinical significance. Int J Gen Med 2021; 14: 8413-25. google scholar
  4. Shen F, Fang Y, Wu Y, Zhou M, Shen J, Fan X. Metal ions and nanometallic materials in antitumor immunity: Function, application, and perspective. J Nanobiotechnology 2023; 21(1): 20. google scholar
  5. Nunes EA, Manieri TM, Matias AC, Bertuchi FR, da Silva DA, Lago L, et al. Protective effects of neocuproine copper chelator against oxidative damage in NSC34 cells. Mutat Res Genet Toxicol Environ Mutagen 2018; 836(Pt B): 62-71. google scholar
  6. Rakshit A, Khatua K, Shanbhag V, Comba P, Datta A. Cu(2+) selective chelators relieve copper-induced oxidative stress in vivo. Chem Sci 2018; 9(41): 7916-30. google scholar
  7. Nigro E, Stiuso P, Matera MG, Monaco ML, Caraglia M, Maniscalco M, et al. The antiproliferative effects of adiponectin on human lung adenocarcinoma A549 cells and oxidative stress involvement. Pulm Pharmacol Ther 2019; 55: 25-30. google scholar
  8. Lee HM, Lee HJ, Chang JE. Inflammatory cytokine: An attractive target for cancer treatment. Biomedicines 2022; 10(9): 2116. google scholar
  9. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37(4): 277-85. google scholar
  10. Alvarez N, Vina D, Leite CM, Mendes LFS, Batista AA, Ellena J, et al. Synthesis and structural characterization of a series of ternary copper(II)-L-dipeptide-neocuproine complexes. Study of their cytotoxicity against cancer cells including MDA-MB-231, triple negative breast cancer cells. J Inorg Biochem 2020; 203: 110930. google scholar
  11. Starosta R, Bykowska A, Kyziol A, Plotek M, Florek M, Krol J, et al. Copper(I) (pseudo)halide complexes with neocuproine and aminomethylphosphines derived from morpholine and thiomorpholine - in vitro cytotoxic and antimicrobial activity and the interactions with DNA and serum albumins. Chem Biol Drug Des 2013; 82(5): 579-86. google scholar
  12. Hsu NS, Tehei M, Hossain MS, Rosenfeld A, Shiddiky MJA, Sluyter R, et al. Oxi-Redox selective breast cancer treatment: an ın vitro study of theranostic ın-based oxide nanoparticles for controlled generation or prevention of oxidative stress. ACS Appl Mater Interfaces 2021; 13(2): 2204-17. google scholar
  13. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 2006; 8 Suppl 2(Suppl 2): S2. google scholar
  14. Remigante A, Cordaro M, Morabito R. Redox homeostasis and antioxidant strategies in the pathophysiology. Antioxidants 2024; 13(3): 281. google scholar
  15. Yesilyurt F, Yuca H, Karakaya S, Tekman E, Demirci B, Taghizadehghalehjoughi A, et al. Investigation on effects of walnut essential oil against glutamate toxicity on cortex neuron and LN405 cancer cell lines, diabetes, and some microorganisms. J Essential Oil Res 2023; 35(4): 372–81. google scholar
  16. Yesilyurt F, Özbek H, Hacımüftüoğlu ME, Coşkun AN, Dumlu A, Coşkun O. Anticancer potential of watermelon seed extracts against lung and breast cancer cell lines. Recent Trends Pharm 2024; 2(1): 21-6. google scholar
  17. Demirdogen F, Yesilyurt F, Budak A, Akcay G, Hacimuftuoglu A. Anti-cancer effect of neocuproine on oxidative stress and inflammatory levels induced by neuroblastoma cancer cells. C R Acad Bulg Sci 2024; 77(4): 584–91. google scholar
  18. Sezen S, Yesilyurt F, Özkaraca M, Bayram C, Alaylar B, Güllüce M, et al. Neuroprotective effect of methanol extract of Capparis spinosa L. fruits in an in-vitro experimental model of Parkinson’s disease. J Med Palliat Care 2022; 3(4): 341-6. google scholar
  19. Celik H, Akcay G, Savas AB, Yesilyurt F, Demirdogen F, Ates D, et al. Trolox reduces neuroblastoma-induced oxidative stress and inflammation. Turk Neurosurg 2024; 34(6): 1117-21. google scholar
  20. Berkoz M, Krosniak M. Punicalagin induces apoptosis in A549 cell line through mitochondria-mediated pathway. Gen Physiol Biophys 2020; 39(6): 557-67. google scholar
  21. Liu S, Li Y, Qi W, Zhao Y, Huang A, Sheng W, et al. Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients. Diagn Pathol 2014; 9: 69. google scholar
  22. Brady DC, Crowe MS, Turski ML, Hobbs GA, Yao X, Chaikuad A, et al. Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature 2014; 509(7501): 492-6. google scholar
  23. Guan D, Zhao L, Shi X, Ma X, Chen Z. Copper in cancer: From pathogenesis to therapy. Biomed Pharmacother 2023; 163: 114791. google scholar
  24. Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, et al. Connecting copper and cancer: from transition metal signalling to metalloplasia. Nat Rev Cancer 2022; 22(2): 102-13. google scholar
  25. Springer C, Humayun D, Skouta R. Cuproptosis: Unraveling the mechanisms of copperinduced cell death and its implication in cancer therapy. Cancers (Basel) 2024; 16(3): 647. google scholar
  26. Tang D, Kroemer G, Kang R. Targeting cuproplasia and cuproptosis in cancer. Nat Rev Clin Oncol 2024; 21(5): 370-88. google scholar
  27. Arnal N, de Alaniz MJ, Marra CA. Carnosine and neocuproine as neutralizing agents for copper overload-induced damages in cultured human cells. Chem Biol Interact 2011; 192(3): 257-63. google scholar
  28. Ghasemi M, Turnbull T, Sebastian S, Kempson I. The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int J Mol Sci 2021; 22(23): 12827. google scholar
  29. Frenzel C, Teschke R. Herbal Hepatotoxicity: Clinical characteristics and listing compilation. Int J Mol Sci 2016; 17(5): 588. google scholar
  30. Zhao X, Lin Y, Jiang B, Yin J, Lu C, Wang J, et al. Icaritin inhibits lung cancer-induced osteoclastogenesis by suppressing the expression of IL-6 and TNF-a and through AMPK/ mTOR signaling pathway. Anticancer Drugs 2020; 31(10): 1004-11. google scholar
  31. Zafar A, Singh S, Naseem I. Cu(II)-coumestrol interaction leads to ROS-mediated DNA damage and cell death: a putative mechanism for anticancer activity. J Nutr Biochem 2016; 33: 15-27. google scholar
  32. Farhan M. Naringin's prooxidant effect on tumor cells: copper's role and therapeutic implications. Pharmaceuticals (Basel) 2022; 15(11): 1431. google scholar
  33. Feng Q, Huo C, Wang M, Huang H, Zheng X, Xie M. Research progress on cuproptosis in cancer. Front Pharmacol 2024; 15: 1290592. google scholar