Original Article

Anticancer Effects of ZnO/CNT@Fe3O4 in AML-Derived KG1 Cells: Shedding Light on Promising Potential of Metal Nanoparticles in Acute Leukemia


Background: Therapeutic approaches for acute myeloid leukemia (AML) have remained largely unchanged for over 40 years and cytarabine and an anthracycline (e.g., daunorubicin) backbone is the main induction therapy for these patients. Resistance to chemotherapy is the major clinical challenge and contributes to short-term survival with a high rate of disease recurrence. Given the established efficacy of nanoparticles in cancer treatment, this study was designed to evaluate the anticancer property of our novel nanocomposite in the AML-derived KG1 cells.

Materials and Methods: To assess the anti-leukemic effects of our nanocomposite on AML cells, we used MTT and trypan blue assays. Flow cytometric analysis and q-RT-PCR were also applied to evaluate the impact of nanocomposite on cell cycle and apoptosis.

Results: Our results outlined that ZnO/CNT@Fe3O4 decreased viability and metabolic activity of KG1 cells through induction of G1 arrest by increasing the expression of p21 and p27 cyclin-dependent kinase inhibitors and decreasing c-Myc transcription. Moreover, ZnO/CNT@Fe3O4 markedly elevated the percentage of apoptotic cells which was coupled with a significant alteration of Bax and Bcl-2 expressions. Synergistic experiments showed that ZnO/CNT@Fe3O4 enhances the cytotoxic effects of Vincristine on KG1 cells.

Conclusion: In conclusion, this study sheds light on the potent anti-leukemic effects of ZnO/CNT@Fe3O4 and provides evidence for the application of this agent in the treatment of acute myeloid leukemia.


1. Kroschinsky F, Stölzel F, Bonin SV, et al. New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. Crit Care . 2017;21(1):89.

2. Song, X, Peng Y, Wang X, et al. Incidence, survival, and risk factors for adults with acute myeloid leukemia not otherwise specified and acute myeloid leukemia with recurrent genetic abnormalities: analysis of the surveillance, epidemiology, and end results (SEER) database, 2001–2013. Acta Haematol. 2018;139(2):115-127.
3. Lai C, Doucette K, Norsworthy K. Recent drug approvals for acute myeloid leukemia. J Hematol Oncol. 2019;12(1):100.
4. Medeiros BC, Chan SM, Daver NG, et al. Optimizing survival outcomes with post‐remission therapy in acute myeloid leukemia. Am J Hematol. 2019;94(7):803-811.
5. Schirrmacher V. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol. 2019;54(2):407-419.
6. Mi Y, Shao Z, Vang J, et al. Application of nanotechnology to cancer radiotherapy. Cancer Nanotechnol. 2016. 7(1):11.
7. Wang X, Zhang R, Wu C, et al. The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance. J Biomed Mater Res A. 2007;80(4):852-60.
8. Amreddy N, Babu A, Muralidharan R, et al. Recent advances in nanoparticle-based cancer drug and gene delivery. Adv Cancer Res. 2018;137:115-170.
9. Wang J, Gao S, Wang S, et al. Zinc oxide nanoparticles induce toxicity in CAL 27 oral cancer cell lines by activating PINK1/Parkin-mediated mitophagy. Int J Nanomedicine. 2018;13:3441-3450.
10. Sadri A, Changizi V, Eivazadeh N. Evaluation of glioblastoma (U87) treatment with ZnO nanoparticle and X-ray in spheroid culture model using MTT assay. Radiat Phys Chem. 2015. 115: 17-21.
11. Farasat M, Niazvand F, Khorsandi L. Zinc oxide nanoparticles induce necroptosis and inhibit autophagy in MCF-7 human breast cancer cells. Biologia. 2020. 75(1):161-174.
12. Xie Y, Liu D, Cai C, et al. Size-dependent cytotoxicity of Fe3O4 nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells. Int J Nanomedicine. 2016;11:3557-70.
13. Tanino R, et al. Anticancer Activity of ZnO Nanoparticles against Human Small-Cell Lung Cancer in an Orthotopic Mouse Model. Mol Cancer Ther. 2020;19(2):502-512.
14. Yousefi AM, Safaroghli-Azar A, Fakhroueian Z, et al. ZnO/CNT@ Fe3O4 induces ROS-mediated apoptosis in chronic myeloid leukemia (CML) cells: an emerging prospective for nanoparticles in leukemia treatment. Artif Cells Nanomed Biotechnol. 2020;48(1):735-745.
15. Bashash D, Ghaffari SH, Zaker F, et al. BIBR 1532 increases arsenic trioxide-mediated apoptosis in acute promyelocytic leukemia cells: therapeutic potential for APL. Anticancer Agents Med Chem. 2013;13(7):1115-25.
16. Safaroghli-Azar A, Bashash D, Sadreazami P, et al. PI3K-δ inhibition using CAL-101 exerts apoptotic effects and increases doxorubicin-induced cell death in pre-B-acute lymphoblastic leukemia cells. Anticancer Drugs. 2017. 28(4): 436-445.
17. Javidparvar A, Ramezanzadeh B, Ghasemi E. Effect of various spinel ferrite nanopigments modified by amino propyl trimethoxy silane on the corrosion inhibition properties of the epoxy nanocomposites. Corrosion. 2016. 72(6): 761-774.
18. Ankamwar B, Thorat A. Rod-shaped magnetite nano/microparticles synthesis at ambient temperature. Jchem. 2013.
19. Zhang Y, Shao L, Liu B, et al. Effect of molecular weight of liquid polysulfide on water and organic solvent resistances of waterborne polyurethane/polysulfide copolymer. Prog Org Coat. 2017;112: 75-85.
20. Jmiai A, El Ebrahimi B, Tara A, et al. Application of Zizyphus Lotuse-pulp of Jujube extract as green and promising corrosion inhibitor for copper in acidic medium. J Mol Liq. 2018; 268: 102-113.
21. Wan S, He F, Wu J, et al. Rapid and highly selective removal of lead from water using graphene oxide-hydrated manganese oxide nanocomposites. J Hazard Mater. 2016;314:32-40
22. Cui M, Ren S, Zhao H, et al. Polydopamine coated graphene oxide for anticorrosive reinforcement of water-borne epoxy coating. Chem Eng J. 2018. 335: 255-266.
23. Li M, Liu Q, Jia Z, et al. Electrophoretic deposition and electrochemical behavior of novel graphene oxide-hyaluronic acid-hydroxyapatite nanocomposite coatings. Appl Surf Sci. 2013. 284: 804-810.
24. Javidparvar AA, Naderi R, Ramezanzadeh B, et al. Graphene oxide as a pH-sensitive carrier for targeted delivery of eco-friendly corrosion inhibitors in chloride solution: Experimental and theroretical investigations. J Ind Eng Chem. 2019. 72: 96-213.
25. Sui J, Li J, Li Z, et al. Synthesis and characterization of one-dimensional magnetic photocatalytic CNTs/Fe3O4–ZnO nanohybrids. Mater Chem Phys. 2012. 134(1): 229-234.
26. Olm E, Jönsson-Videsäter K, Ribera-Cortada I, et al. Selenite is a potent cytotoxic agent for human primary AML cells. Cancer lett. 2009; 282(1): 116-123.
27. Aswathanarayan JB, Vittal RR, Muddegowda U. Anticancer activity of metal nanoparticles and their peptide conjugates against human colon adenorectal carcinoma cells. Artif Cells Nanomed Biotechnol. 2018;46(7):1444-1451.
28. Ostrovsky S, Kazimirsky G, Gedanken A, Brodie C. Selective cytotoxic effect of ZnO nanoparticles on glioma cells. Nano Research. 2009;2(11):882-90.
29. Hackl H, Astanina K, Wieser R. Molecular and genetic alterations associated with therapy resistance and relapse of acute myeloid leukemia. J Hematol Oncol. 2017;10(1):51.
30. Khandel P, Kumar YR, Kumar SD, et al. Biogenesis of metal nanoparticles and their pharmacological applications: present status and application prospects. J Nanostructure Chem. 2018; 8(3): 217-254.
31. Bisht G, Rayamajhi S, Kc B, et al. Synthesis, characterization, and study of in vitro cytotoxicity of ZnO-Fe3O4 magnetic composite nanoparticles in human breast cancer cell line (MDA-MB-231) and mouse fibroblast (NIH 3T3). Nanoscale Res Lett. 2016;11(1):537
32. Ostrovsky S, Kazimirsky G, Gedanken A, et al. Selective cytotoxic effect of ZnO nanoparticles on glioma cells. Nano Res. 2009. 2(11): 882-890.
33. Khan MI, Mohammad A, patil G, et al. Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles. Biomaterials. 2012. 33(5): 1477-88.
34. Alarifi S, Ali H, Alkahtani S, et al. Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage by nano-sized gadolinium oxide. Int J Nanomedicine. 2017;12:4541-4551.
35. Sirelkhatim AH, Mahmoud SH, Seeni A, et al. Preferential cytotoxicity of ZnO nanoparticle towards cervical cancer cells induced by ROS-mediated apoptosis and cell cycle arrest for cancer therapy. J Nanoparticle Res. 2016. 18(8):219.
IssueVol 16, No 3 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijhoscr.v16i3.10136
Acute myeloid leukemia (AML); Zinc oxide; Carbon nanotubes; Iron oxide; Nanoparticles; Vincristine

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Yousefi A-M, Pourbagheri-Sigaroodi A, Fakhroueian Z, Salari S, Fateh K, Momeny M, Bashash D. Anticancer Effects of ZnO/CNT@Fe3O4 in AML-Derived KG1 Cells: Shedding Light on Promising Potential of Metal Nanoparticles in Acute Leukemia. Int J Hematol Oncol Stem Cell Res. 2022;16(3):140-150.