ANTI-PROLIFERATIVE EFFECTS OF CU(PHEN)(C-DIMETHYLGLYCINE)NO3 ON HT-29 AND A2780 CANCER CELL LINES: A POTENTIAL CHEMOTHERAPEUTIC APPROACH

Authors

  • NURFARAHDILLA ZAINUDIN Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia https://orcid.org/0009-0008-3363-7127
  • NG CHIN THENG Department of Physiology, Asian Institute of Medicine, Science and Technology, Kedah, Malaysia
  • FONG LAI YEN Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia. https://orcid.org/0000-0001-7912-6746
  • YONG YOKE KEONG Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia. https://orcid.org/0000-0002-9442-7456
  • MUHAMMAD NAZRUL HAKIM Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia. https://orcid.org/0000-0002-4710-3467
  • ZURAINI AHMAD Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

DOI:

https://doi.org/10.22159/ajpcr.2025v18i6.54576

Keywords:

Copper(II) Complex, Anti-Proliferative Activity, Cancer Cell Lines, IC50, Apoptosis Assay

Abstract

Objectives: This study aimed to evaluate the in vitro anti-proliferative properties of Cu(Phen)(C-dimethylglycine)NO3 on human cancer cell lines. Specifically, the study investigated its effects on the proliferation of colorectal carcinoma (HT-29) and ovarian carcinoma (A2780) cells, determined the IC50 values, measured caspase-9 activity, and assessed the degree of DNA fragmentation.

Methods: The anti-proliferative and apoptotic effects of standardized Cu(phen)(C-dimethylglycine)NO3 were evaluated at varying concentrations (1, 2, 5, 10, 15, and 20 µM) over 24, 48, and 72 hours. Cell viability was assessed using the MTT assay, while caspase-9 activity was measured using fluorometric assay kits and a fluorophotometer. DNA fragmentation was analyzed using the Cell Death Detection ELISA Plus kit.

Results: The results demonstrated a time- and concentration-dependent reduction in cell viability for both cell lines. Notably, A2780 cells exhibited a lower IC50 (1.76 ± 0.406 µM at 72 hours) compared to HT-29 cells (7.03 ± 0.635 µM), indicating greater sensitivity. However, the compound did not significantly alter caspase-9 expression nor induce DNA fragmentation when compared to the control.

Conclusion: Cu(phen)(C-dimethylglycine)NO3 exerts a significant anti-proliferative effect without triggering apoptosis, suggesting a non-apoptotic mechanism of cytotoxicity that warrants further investigation.

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Author Biography

FONG LAI YEN, Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia.

 

 

References

Tisato F, Marzano C, Porchia M, Pellei M, Santini C. Copper in diseases and treatments, and copper-based anticancer strategies. Med Res Rev. 2010;30(4):708-49. doi: 10.1002/med.20174, PMID 19626597

Ji P, Wang P, Chen H, Xu Y, Ge J, Tian Z, et al. Potential of copper and copper compounds for anticancer applications. Pharmaceuticals (Basel). 2023;16(2):234. doi: 10.3390/ph16020234, PMID 37259382

Tisato F, Marzano C, Porchia M, Pellei M, Santini C. Copper in diseases and treatments, and copper-based anticancer strategies. Med Res Rev. 2020;40(1):111-33. doi: 10.1002/med.21612

Santini C, Pellei M, Gandin V, Porchia M, Tisato F, Marzano C. Advances in copper complexes as anticancer agents. Chem Rev. 2021;121(2):813-57. doi: 10.1021/acs.chemrev.0c00230.

Suntharalingam K, Tang LJ, Lu YJ. Copper-based metallodrugs: Strategies to target cancer cells. Front Chem. 2023;11:1156275. doi: 10.3389/fchem.2023.1156275

Weder JE, Dillon CT, Hambley TW, Kennedy BJ, Lay PA, Biffin JR, et al. Copper complexes of non-steroidal anti-inflammatory drugs: An opportunity yet to be realized. Coord Chem Rev. 2002;232(1-2):95- 126. doi: 10.1016/S0010-8545(02)00086-3

Gonzalez-Vilchez F, Vilaplana RA. Copper complexes as potential anti-inflammatory and anticancer agents. J Inorg Biochem. 2005;99(4):771- 9. doi: 10.1016/j.jinorgbio.2004.12.009

Noyce JO, Michels H, Keevil CW. Inactivation of influenza A virus on copper versus stainless steel surfaces. Appl Environ Microbiol. 2007;73(8):2748-50. doi: 10.1128/AEM.01139-06, PMID 17259354

Kubo AL, Rausalu K, Savest N, Žusinaite E, Vasiliev G, Viirsalu M, et al. Antibacterial and antiviral effects of ag, Cu and Zn metals, respective nanoparticles and filter materials thereof against coronavirus SARS-CoV-2 and influenza A virus. Pharmaceutics. 2022;14(12):2549. doi: 10.3390/pharmaceutics14122549, PMID 36559043

Borkow G, Gabbay J. Putting copper into action: Copper-impregnated products with potent biocidal activities. FASEB J. 2004;18(14):1728- 30. doi: 10.1096/fj.04-2029fje, PMID 15345689

Linder MC. The relationship of copper to DNA damage and damage prevention in humans. Mutat Res. 2012;733(1-2):83-91. doi: 10.1016/j. mrfmmm.2012.03.010, PMID 23463874

Molinaro C, Martoriati A, Pelinski L, Cailliau K. Copper complexes as anticancer agents targeting topoisomerases I and II. Cancers (Basel).

;12(10):2863. doi: 10.3390/cancers12102863, PMID 33027952

Wojtowicz K, Nowicki M. The characterization of the sensitive ovarian cancer cell lines A2780 and W1 in response to ovarian CAFs. Biochem Biophys Res Commun. 2023;662:1-7. doi: 10.1016/j.bbrc.2023.04.059, PMID 37088000

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. doi: 10.3390/ ijms222312827, PMID 34884632

Chiong HS, Yong YK, Ahmad Z, Sulaiman MR, Zakaria ZA, Yuen KH, et al. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages. Int J Nanomedicine. 2013;8(8):1245-55. doi: 10.2147/IJN.S42801, PMID 23569374

Seng HL, Tan KW, Maah MJ, Tan WT, Hamada H, Chikira M, et al. Copper(II) complexes of methylated glycine derivatives: Effect of methyl substituent on their DNA binding and nucleolytic property. Polyhedron. 2009;28(11):2219-27. doi: 10.1016/j.poly.2009.03.022

Gao L, Zhang A. Copper-instigated modulatory cell mortality mechanisms and progress in oncological treatment investigations. Front Immunol. 2023;14:1236063. doi: 10.3389/fimmu.2023.1236063, PMID 37600774

AshaRani PV, Low Kah Mun G, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2009;3(2):279-90. doi: 10.1021/nn800596w, PMID 19236062

Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature. 1998;391(6662):43-50. doi: 10.1038/34112, PMID 9422506

Raikar PR, Dandagi PM. Funtionalized polymeric nanoparticles: A novel targeted approach for oncology care. Int J Appl Pharm. 2021;13(6):1-18. doi: 10.22159/ijap.2021v13i6.42714

Ahmed T, Ramasamy K, Ramya S. An in silico and in vitro evaluation of cytotoxicity, apoptotic activityand gene expression modulation of sarsasapogenin in human colorectal cancer cell lines HT-29. Int J Appl Pharm. 2024;16(4):84-91.

Mocellin S, Rossi CR, Pilati P, Nitti D. Tumor necrosis factor, cancer and anticancer therapy. Cytokine Growth Factor Rev. 2005;16(1):35- 53. doi: 10.1016/j.cytogfr.2004.11.001, PMID 15733831

Bhutadiya VL, Mistry KN. A review on bioactive phytochemicals and It’s mechanism on cancer treatment and prevention by targeting Multiple cellular Signaling pathways. Int J Pharm Pharm Sci. 2021;13(12):15-9. doi: 10.22159/ijpps.2021v13i12.42798

Published

07-06-2025

How to Cite

NURFARAHDILLA ZAINUDIN, et al. “ANTI-PROLIFERATIVE EFFECTS OF CU(PHEN)(C-DIMETHYLGLYCINE)NO3 ON HT-29 AND A2780 CANCER CELL LINES: A POTENTIAL CHEMOTHERAPEUTIC APPROACH”. Asian Journal of Pharmaceutical and Clinical Research, vol. 18, no. 6, June 2025, pp. 76-80, doi:10.22159/ajpcr.2025v18i6.54576.

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