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

Overview

Journal Int J Hematol Oncol Stem Cell Res

Specialty Hematology

Date 2023 Jan 25

PMID 36694699

Authors

Amir-Mohammad Yousefi

Atieh Pourbagheri-Sigaroodi

Zahra Fakhroueian

Sina Salari

Kosar Fateh

Majid Momeny

Davood Bashash

Affiliations

Soon will be listed here.

Abstract

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. 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. Our results outlined that ZnO/CNT@FeO 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@FeO 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@FeO enhances the cytotoxic effects of Vincristine on KG1 cells. In conclusion, this study sheds light on the potent anti-leukemic effects of ZnO/CNT@FeO and provides evidence for the application of this agent in the treatment of acute myeloid leukemia.

References

Alarifi S, Ali H, Alkahtani S, Alessia M . Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage by nano-sized gadolinium oxide. Int J Nanomedicine. 2017; 12:4541-4551. PMC: 5485892. DOI: 10.2147/IJN.S139326. View

Tanino R, Amano Y, Tong X, Sun R, Tsubata Y, Harada M . Anticancer Activity of ZnO Nanoparticles against Human Small-Cell Lung Cancer in an Orthotopic Mouse Model. Mol Cancer Ther. 2019; 19(2):502-512. DOI: 10.1158/1535-7163.MCT-19-0018. View

Khan M, Mohammad A, Patil G, Naqvi S, Chauhan L, Ahmad I . Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles. Biomaterials. 2011; 33(5):1477-88. DOI: 10.1016/j.biomaterials.2011.10.080. View

Amreddy N, Babu A, Muralidharan R, Panneerselvam J, Srivastava A, Ahmed R . Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery. Adv Cancer Res. 2018; 137:115-170. PMC: 6550462. DOI: 10.1016/bs.acr.2017.11.003. View

Olm E, Jonsson-Videsater K, Ribera-Cortada I, Fernandes A, Eriksson L, Lehmann S . Selenite is a potent cytotoxic agent for human primary AML cells. Cancer Lett. 2009; 282(1):116-23. DOI: 10.1016/j.canlet.2009.03.010. View

Aswathanarayan J, Vittal R, Muddegowda U . Anticancer activity of metal nanoparticles and their peptide conjugates against human colon adenorectal carcinoma cells. Artif Cells Nanomed Biotechnol. 2017; 46(7):1444-1451. DOI: 10.1080/21691401.2017.1373655. View

Wang X, Zhang R, Wu C, Dai Y, Song M, Gutmann S . The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance. J Biomed Mater Res A. 2006; 80(4):852-60. DOI: 10.1002/jbm.a.30901. View

Schirrmacher V . From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review). Int J Oncol. 2018; 54(2):407-419. PMC: 6317661. DOI: 10.3892/ijo.2018.4661. View

Kroschinsky F, Stolzel F, von Bonin S, Beutel G, Kochanek M, Kiehl M . New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. Crit Care. 2017; 21(1):89. PMC: 5391608. DOI: 10.1186/s13054-017-1678-1. View

10.

Yousefi A, Safaroghli-Azar A, Fakhroueian Z, Bashash D . ZnO/CNT@FeO 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. DOI: 10.1080/21691401.2020.1748885. View

11.

Medeiros B, Chan S, Daver N, Jonas B, Pollyea D . Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia. Am J Hematol. 2019; 94(7):803-811. PMC: 6593671. DOI: 10.1002/ajh.25484. View

12.

Safaroghli-Azar A, Bashash D, Sadreazami P, Momeny M, Ghaffari S . 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. DOI: 10.1097/CAD.0000000000000477. View

13.

Mi Y, Shao Z, Vang J, Kaidar-Person O, Wang A . Application of nanotechnology to cancer radiotherapy. Cancer Nanotechnol. 2017; 7(1):11. PMC: 5167776. DOI: 10.1186/s12645-016-0024-7. View

14.

Lai C, Doucette K, Norsworthy K . Recent drug approvals for acute myeloid leukemia. J Hematol Oncol. 2019; 12(1):100. PMC: 6749668. DOI: 10.1186/s13045-019-0774-x. View

15.

Bisht G, Rayamajhi S, Kc B, Paudel S, Karna D, Shrestha B . 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. PMC: 5135709. DOI: 10.1186/s11671-016-1734-9. View

16.

Wang J, Gao S, Wang S, Xu Z, Wei L . 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. PMC: 6016020. DOI: 10.2147/IJN.S165699. View

17.

Bashash D, Ghaffari S, Zaker F, Kazerani M, Hezave K, Hassani S . 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. DOI: 10.2174/18715206113139990126. View

18.

Song X, Peng Y, Wang X, Chen Y, Jin L, Yang T . 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,.... Acta Haematol. 2018; 139(2):115-127. DOI: 10.1159/000486228. View

19.

Wan S, He F, Wu J, Wan W, Gu Y, Gao B . Rapid and highly selective removal of lead from water using graphene oxide-hydrated manganese oxide nanocomposites. J Hazard Mater. 2016; 314:32-40. DOI: 10.1016/j.jhazmat.2016.04.014. View

20.

Xie Y, Liu D, Cai C, Chen X, Zhou Y, Wu L . 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. PMC: 4973727. DOI: 10.2147/IJN.S105575. View