Volume 30, Issue 1 (March 2026)                   Physiol Pharmacol 2026, 30(1): 1-9 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
namvar aghdash S, Mahdavi M, Foroughi G. Complex of zinc (II) methylthiosemicarbazone induces cytotoxicity, antiproliferative, and apoptosis effects in human K562 leukemia. Physiol Pharmacol 2026; 30 (1) :1-9
URL: http://ppj.phypha.ir/article-1-2483-en.html
Complex of zinc (II) methylthiosemicarbazone induces cytotoxicity, antiproliferative, and apoptosis effects in human K562 leukemia
Simin Namvar aghdash , Majid Mahdavi , Golsa Foroughi
Abstract:   (1890 Views)

Introduction: Methylthiosemicarbazones (MTSCs) are compounds with various biological properties. Some studies have shown that their metal complexes have potential cytotoxic effects on numerous cancers. In this study, the effects of zinc (II)-methylthiosemicarbazone complex (Zn-MTC) on the human chronic myelogenous leukemia K562 cell line were evaluated.
Methods: In this experimental study, K562 cells were treated with different doses of Zn-MTC for 24, 48, and 72 hours. We investigated whether this compound could induce cytotoxicity and apoptosis in K562 cells using the MTT assay, fluorescence microscopy, and flow cytometry.
Results: Our findings indicated that Zn-MTC inhibited the growth of K562 cells and induced apoptosis in a time- and dose-dependent manner. The IC50 of the complex was 100 µM after 72 hours of incubation. Morphological changes and sub-G1 cell cycle arrest confirmed the induction of apoptosis in K562 cells treated with the IC50 concentration of this compound.
Conclusion: Given its antiproliferative and apoptosis-inducing effects, Zn-MTC can be proposed for further pharmaceutical evaluation in the treatment of chronic myeloid leukemia (CML) in the future.

Keywords: Methylthiosemicarbazone, Apoptosis, Cytotoxicity, cell cycle, K562 cell line.
Full-Text [PDF 676 kb]   (203 Downloads)    
Type of Manuscript: Short communication | Subject: Others
References
1. Bonaccorso C, Marzo T, La Mendola D. Biological applications of thiocarbohydrazones and their metal complexes: A perspective review. Pharmaceuticals 2019; 13: 4. [DOI:10.3390/ph13010004]
2. Brockman R W, Thomson J R, Bell M J, Skipper H E. Observations on the antileukemic activity of pyridine-2-carboxaldehyde thiosemicarbazone and thiocarbohydrazone. Cancer Research 1956a; 16: 167-170.
3. Cao Q, Wang Q, Wu X, Zhang Q, Huang J, Chen Y, et al. A literature review: mechanisms of antitumor pharmacological action of leonurine alkaloid. Frontiers in Pharmacology 2023; 14: 1272546. [DOI:10.3389/fphar.2023.1272546]
4. Chhikara B S, Parang K. Global Cancer Statistics 2022: the trends projection analysis. Chemical Biology Letters 2023; 10: 451-451.
5. Clarke C J, Holyoake T L. Preclinical approaches in chronic myeloid leukemia: from cells to systems. Experimental hematology 2017; 47: 13-23. [DOI:10.1016/j.exphem.2016.11.005]
6. Deininger M W, Shah N P, Altman J K, Berman E, Bhatia R, Bhatnagar B, et al. Chronic myeloid leukemia, version 2.2021, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network 2020; 18: 1385-1415. [DOI:10.6004/jnccn.2020.0047]
7. Elmore S. Apoptosis: a review of programmed cell death. Toxicologic Pathology 2007; 35: 495-516. [DOI:10.1080/01926230701320337]
8. Garbuz O, Ceban E, Istrati D, Railean N, Toderas I, Gulea A. Thiosemicarbazone-based compounds: cancer cell inhibitors with antioxidant properties. Molecules 2025; 30: 2077. [DOI:10.3390/molecules30092077]
9. Green D R. Cell death and cancer. Cold Spring Harbor Perspectives in Biology 2022; 14: a041103. [DOI:10.1101/cshperspect.a041103]
10. Hanahan D, Weinberg R A. Hallmarks of cancer: the next generation. cell 2011; 144: 646-674. [DOI:10.1016/j.cell.2011.02.013]
11. Hosseini-Yazdi S A, Mirzaahmadi A, Khandar A A, Mahdavi M, Rahimian A, Eigner V, et al. Copper, nickel and zinc complexes of a new water-soluble thiosemicarbazone ligand: Synthesis, characterization, stability and biological evaluation. Journal of Molecular Liquids 2017; 248: 658-667. [DOI:10.1016/j.molliq.2017.10.068]
12. Kaleem B, Shahab S, Ahmed N, Shamsi T S. Chronic myeloid leukemia-prognostic value of mutations. Asian Pacific Journal of Cancer Prevention 2015; 16: 7415-7423. [DOI:10.7314/APJCP.2015.16.17.7415]
13. Kalındemirtaş F D, Kaya B, Bener M, Şahin O, Kuruca S E, Demirci T B, et al. Iron (III) complexes based on tetradentate thiosemicarbazones: Synthesis, characterization, radical scavenging activity and in vitro cytotoxicity on K562, P3HR1 and JURKAT cells. Applied Organometallic Chemistry 2021; 35: e6157. [DOI:10.1002/aoc.6157]
14. Kaur H, Gupta M. Recent advances in thiosemicarbazones as anticancer agents. International Journal of Pharmacy and Biological Sciences 2018; 8: 259-265.
15. Kolenova A, Maloney K W, Hunger S P. Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia in lymphoid blast crisis. Journal of Pediatric Hematology/Oncology 2016; 38: e193-e195. [DOI:10.1097/MPH.0000000000000582]
16. Lakshmipriya T, Soumya T, Jayasree P, Manish Kumar P. Selective induction of DNA damage, G2 abrogation, and mitochondrial apoptosis by leaf extract of traditional medicinal plant Wrightia arborea in K562 cells. Protoplasma 2018; 255: 203-216. [DOI:10.1007/s00709-017-1137-5]
17. Li Q, Huang Z, Gao M, Cao W, Xiao Q, Luo H, et al. Blockade of Y177 and nuclear translocation of Bcr-Abl inhibits proliferation and promotes apoptosis in chronic myeloid leukemia cells. International Journal of Molecular Sciences 2017; 18: 537. [DOI:10.3390/ijms18030537]
18. Mahdavi M, Lavi M M, Yekta R, Moosavi M A, Nobarani M, Balalaei S, et al. Evaluation of the cytotoxic, apoptosis inducing activity and molecular docking of spiroquinazolinone benzamide derivatives in MCF-7 breast cancer cells. Chemico-Biological Interactions 2016; 260: 232-242. [DOI:10.1016/j.cbi.2016.10.004]
19. Mahdavi M, Yazdanparast R. Gnidilatimonoein from Daphne mucronata induces differentiation and apoptosis in leukemia cell lines. Archives of Pharmacal Research 2007; 30: 177-181. [DOI:10.1007/BF02977692]
20. Moon J, Kitty I, Renata K, Qin S, Zhao F, Kim W. DNA damage and its role in cancer therapeutics. International Journal of Molecular Sciences 2023; 24: 4741. [DOI:10.3390/ijms24054741]
21. Nath P, Datta A, Adhikari S. Recent advances of metal-based anticancer agents and their in vivo potential against various types of malignancies. Handbook of animal models and its uses in cancer research 2022: 1-28. [DOI:10.1007/978-981-19-1282-5_47-1]
22. Ngoepe M P, Clayton H S. Metal complexes as DNA synthesis and/or repair inhibitors: anticancer and antimicrobial agents. Pharmaceutical Fronts 2021; 3: e164-e182. [DOI:10.1055/s-0041-1741035]
23. Parsa F G, Feizi M A H, Safaralizadeh R, Hosseini-Yazdi S A, Mahdavi M. Molecular mechanisms of apoptosis induction in K562 and KG1a leukemia cells by a water-soluble copper (II) thiosemicarbazone complex. Journal of Biological Inorganic Chemistry 2020; 25: 383-394. [DOI:10.1007/s00775-020-01769-0]
24. Savir S, Liew J W K, Vythilingam I, Lim Y A L, Tan C H, Sim K S, et al. Nickel (II) complexes with polyhydroxybenzaldehyde and O, N, S tridentate thiosemicarbazone ligands: Synthesis, cytotoxicity, antimalarial activity, and molecular docking studies. Journal of Molecular Structure 2021; 1242: 130815. [DOI:10.1016/j.molstruc.2021.130815]
25. Shakya B, Yadav P N. Thiosemicarbazones as potent anticancer agents and their modes of action. Mini Reviews in Medicinal Chemistry 2020; 20: 638-661. [DOI:10.2174/1389557519666191029130310]
26. Sheth U V. Determination of toxicity through cytotoxicity assays. Biosafety assessment of probiotic potential: New York, NY: Springer US 2022: 137-147. [DOI:10.1007/978-1-0716-2509-5_15]
27. Siegel R L, Miller K D, Wagle N S, Jemal A. Cancer statistics, 2023. CA: a cancer journal for clinicians 2023; 73: 17-48. [DOI:10.3322/caac.21763]
28. Singh S, Mandal M K, Masih A, Saha A, Ghosh S K, Bhat H R, et al. 1, 3, 5-Triazine: A versatile pharmacophore with diverse biological activities. Archiv der Pharmazie 2021; 354: 2000363. [DOI:10.1002/ardp.202000363]
29. Taylor R C, Cullen S P, Martin S J. Apoptosis: controlled demolition at the cellular level. Nature Reviews Molecular Cell Biology 2008; 9: 231-241. [DOI:10.1038/nrm2312]
30. Vermes I, Haanen C, Steffens-Nakken H, Reutellingsperger C. A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. Journal of Immunological Methods 1995; 184: 39-51. [DOI:10.1016/0022-1759(95)00072-I]
31. Xu W-f, Wang Z-j, Li K, Shen Y-q, Lu K, Lv X-y, et al. Huai qi Huang-induced apoptosis via down-regulating PRKCH and inhibiting RAF/MEK/ERK pathway in Ph+ leukemia cells. Current Medical Science 2020; 40: 354-362. [DOI:10.1007/s11596-020-2181-5]
32. Yazdanparast R, Moosavi M A, Mahdavi M, Sanati M H. 3-Hydrogenkwadaphnin from Dendrostellera lessertii induces differentiation and apoptosis in HL-60 cells. Planta Medica 2005; 71: 1112-1117. [DOI:10.1055/s-2005-873165]
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.