A novel LL-37@NH2@Fe3O4 inhibits the proliferation of the leukemia K562 cells: in-vitro study.
Humans
K562 Cells
Cell Proliferation
/ drug effects
Antimicrobial Cationic Peptides
/ pharmacology
Cathelicidins
Apoptosis
/ drug effects
Tumor Suppressor Protein p53
/ metabolism
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Magnetite Nanoparticles
/ chemistry
Magnetic Iron Oxide Nanoparticles
/ chemistry
bcl-2-Associated X Protein
/ metabolism
Cell Survival
/ drug effects
Antineoplastic Agents
/ pharmacology
Apoptosis
Bax
Bcl-2
K562 cells
NH2@LL-37@Fe3O4 nanoparticles
TP53
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
05
04
2024
accepted:
02
09
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
27
9
2024
Statut:
epublish
Résumé
LL-37 can inhibit the growth of K562 cancer cells when it is conjugated with iron oxide nanoparticles. In this study, Fe3O4 nanoparticles were synthesized using the co-precipitation method and then modified with the LL-37 peptide through an NH2 bridge. The accuracy of the synthesis process was confirmed through various analytical tests, including FTIR, XRD, FESEM, and EDX. To assess the treatment's effectiveness, a viability test was carried out on K562 leukemia cells and normal peripheral blood mononuclear cells. In addition, flow cytometry and Hoechst staining were used to investigate the mechanism of action of the drug. The expression levels of the Bcl-2, Bax, and TP53 genes in the treated cells and the control group were measured using qRT-PCR. The results indicated that the size of the nanoparticles ranged between 34 and 40 nm. The NH2@LL-37@Fe3O4 nanoparticles more effectively inhibited the growth of cancer cells in a concentration-dependent manner, as compared to Fe3O4 alone. Further analysis revealed that apoptosis occurred through increased expression of TP53 and Bax genes compared to the Bcl-2 gene. Therefore, induction of apoptosis and inhibition of growth in K562 cells was attributed to the impact of iron oxide magnetic nanoparticles conjugated with the LL-37 peptide through the TP53/Bax/Bcl-2 pathway.
Identifiants
pubmed: 39333586
doi: 10.1038/s41598-024-71946-7
pii: 10.1038/s41598-024-71946-7
doi:
Substances chimiques
Antimicrobial Cationic Peptides
0
Cathelicidins
0
Tumor Suppressor Protein p53
0
Proto-Oncogene Proteins c-bcl-2
0
Magnetite Nanoparticles
0
bcl-2-Associated X Protein
0
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22245Informations de copyright
© 2024. The Author(s).
Références
Niemirowicz, K., Prokop, I., Wilczewska, A. Z., Wnorowska, U., Piktel, E., Wątek, M., et al. Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells. International journal of nanomedicine. 3843–53 (2015).
Bowdish, D. M., Davidson, D. J., Scott, M. G. & Hancock, R. E. Immunomodulatory activities of small host defense peptides. Antimicrob. Agents Chemother. 49(5), 1727–1732 (2005).
doi: 10.1128/AAC.49.5.1727-1732.2005
Chen, X. et al. Human cathelicidin antimicrobial peptide suppresses proliferation, migration and invasion of oral carcinoma HSC-3 cells via a novel mechanism involving caspase-3 mediated apoptosis. Mol. Med. Rep. 22(6), 5243–5250 (2020).
doi: 10.3892/mmr.2020.11629
Mori, T. et al. Enhancing the anticancer efficacy of a LL-37 peptide fragment analog using peptide-linked PLGA conjugate micelles in tumor cells. Int. J. Pharm. 606, 120891 (2021).
doi: 10.1016/j.ijpharm.2021.120891
Rashid, K. & Ahmad, A. In vitro selective suppression of tumor cells by an oncolytic peptide in pancreatic ductal adenocarcinoma. Int. J. Pept. Res. Ther. 27, 863–873 (2021).
doi: 10.1007/s10989-020-10131-6
Wang, L., Dong, C., Li, X., Han, W. & Su, X. Anticancer potential of bioactive peptides from animal sources. Oncol. Rep. 38(2), 637–651 (2017).
doi: 10.3892/or.2017.5778
Ruan, K., Song, G. & Ouyang, G. Role of hypoxia in the hallmarks of human cancer. J. Cell. Biochem. 107(6), 1053–1062 (2009).
doi: 10.1002/jcb.22214
Wnorowska, U. et al. Nanoantibiotics containing membrane-active human cathelicidin LL-37 or synthetic ceragenins attached to the surface of magnetic nanoparticles as novel and innovative therapeutic tools: Current status and potential future applications. J. Nanobiotechnol. 18, 1–18 (2020).
doi: 10.1186/s12951-019-0566-z
Srivastava, P., Sharma, P. K., Muheem, A. & Warsi, M. H. Magnetic nanoparticles: A review on stratagems of fabrication an d its biomedical applications. Recent Pat. Drug Deliv. Formul. 11(2), 101–113 (2017).
doi: 10.2174/1872211311666170328150747
Gallo, J., Long, N. J. & Aboagye, E. O. Magnetic nanoparticles as contrast agents in the diagnosis and treatment of cancer. Chem. Soc. Rev. 42(19), 7816–7833 (2013).
doi: 10.1039/c3cs60149h
Burger, J. A. Treatment of chronic lymphocytic leukemia. N. Engl. J. Med. 383(5), 460–473 (2020).
doi: 10.1056/NEJMra1908213
Narissa, P., Wheadon, H., Mhairi, C. The application of BH3 mimetics in myeloid leukemias. Cell Death Dis. 12(2), (2021).
Abdulmawjood, B., Costa, B., Roma-Rodrigues, C., Baptista, P. V. & Fernandes, A. R. Genetic biomarkers in chronic myeloid leukemia: What have we learned so far?. Int. J. Mol. Sci. 22(22), 12516 (2021).
doi: 10.3390/ijms222212516
Eslami, F. et al. Down-regulation of Survivin and Bcl-2 concomitant with the activation of caspase-3 as a mechanism of apoptotic death in KG1a and K562 cells upon exposure to a derivative from ciprofloxacin family. Toxicol. Appl. Pharmacol. 409, 115331 (2020).
doi: 10.1016/j.taap.2020.115331
Silveira, M., Silva, I. & Magdalena, A. Synthesis and characterization of Fe 3 O 4-NH 2 and Fe 3 O 4-NH 2-chitosan nanoparticles. Cerâmica 67, 295–300 (2021).
doi: 10.1590/0366-69132021673833101
Piktel, E. et al. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy. J. Nanobiotechnol. 14, 1–23 (2016).
doi: 10.1186/s12951-016-0193-x
Kafi-Ahmadi, L. et al. Co-precipitation synthesis, characterization of CoFe2O4 nanomaterial and evaluation of its toxicity behavior on human leukemia cancer K562 cell line. J. Chil. Chem. Soc. 65(2), 4845–4848 (2020).
doi: 10.4067/S0717-97072020000204845
Abbas, Z. S. et al. Galangin/β-cyclodextrin inclusion complex as a drug-delivery system for improved solubility and biocompatibility in breast cancer treatment. Molecules. 27(14), 4521 (2022).
doi: 10.3390/molecules27144521
Ibrahim, A. A. et al. Pt (II)-thiocarbohydrazone complex as cytotoxic agent and apoptosis inducer in Caov-3 and HT-29 Cells through the P53 and caspase-8 pathways. Pharmaceuticals. 14(6), 509 (2021).
doi: 10.3390/ph14060509
Kadhim, R. J., Karsh, E. H., Taqi, Z. J. & Jabir, M. S. Biocompatibility of gold nanoparticles: In-vitro and In-vivo study. Mater. Today: Proc. 42, 3041–3045 (2021).
Kamaludin, N. F., Ismail, N., Awang, N., Mohamad, R. & Pim, N. U. Cytotoxicity evaluation and the mode of cell death of K562 cells induced by organotin (IV)(2-methoxyethyl) methyldithiocarbamate compounds. J. Appl. Pharm. Sci. 9(6), 010–015 (2019).
doi: 10.7324/JAPS.2019.90602
Zhang, C. et al. Mechanisms involved in the anti-tumor effects of Toosendanin in glioma cells. Cancer Cell Int. 21, 1–13 (2021).
Chamani, E. et al. Evaluation of some genes and proteins involved in apoptosis on human chronic myeloid leukemia cells (K562 cells) by datura innoxia leaves aqueous extract. J. Biomol. Struct. Dynam. 38(16), 4838–4849 (2020).
doi: 10.1080/07391102.2019.1691661
Jabir, M. S. et al. Inhibition of Staphylococcus aureus α-hemolysin production using nanocurcumin capped Au@ ZnO nanocomposite. Bioinorg. Chem. Appl. 2022(1), 2663812 (2022).
doi: 10.1155/2022/2663812
Granados Oliver, J., Reyes Pérez, M., Teja Ruiz, A., Palacios Beas, E., Pérez Labra, M., Barrientos Hernández, F. et al., editors. Characterization by FTIR of sphalerite obtained in the flotation without collector in the presence of ferric iron. Characterization of Minerals, Metals, and Materials 2020; (Springer: 2020).
Jabir, M. S., Nayef, U. M. & Kadhim, W. K. A. Polyethylene glycol-functionalized magnetic (Fe3O4) nanoparticles: A novel DNA-mediated antibacterial agent. Nano Biomed. Eng. 11(1), 18–27 (2019).
doi: 10.5101/nbe.v11i1.p18-27
Smiri M, Guey F, Chemingui H, Dekhil A, Elarbaoui S, Hafiane A. Remove of humic acid from water using magnetite nanoparticles. European Journal of Advanced Chemistry Research. 2020;1(4).
Ooi, F., DuChene, J. S., Qiu, J., Graham, J. O., Engelhard, M. H., Cao, G., et al. A facile solvothermal synthesis of octahedral Fe3O4 nanoparticles. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States; 2015).
Loos, C. et al. Amino-functionalized nanoparticles as inhibitors of mTOR and inducers of cell cycle arrest in leukemia cells. Biomaterials. 35(6), 1944–1953 (2014).
doi: 10.1016/j.biomaterials.2013.11.056
Mader, J. S., Mookherjee, N., Hancock, R. E. & Bleackley, R. C. The human host defense peptide LL-37 induces apoptosis in a calpain-and apoptosis-inducing factor–dependent manner involving bax activity. Mol. Cancer Res. 7(5), 689–702 (2009).
doi: 10.1158/1541-7786.MCR-08-0274
Ahmad, A. & Fawaz, M. A. M. The anticancer mechanism of human antimicrobial peptide LL-37. Neuropharmac. J. 6(3), 261 (2021).
doi: 10.37881/1.635
Guo, D. et al. In vitro cellular uptake and cytotoxic effect of functionalized nickel nanoparticles on leukemia cancer cells. J. Nanosci. Nanotechnol. 8(5), 2301–2307 (2008).
doi: 10.1166/jnn.2008.18272
Chen, X. et al. Roles and mechanisms of human cathelicidin LL-37 in cancer. Cell. Physiol. Biochem. 47(3), 1060–1073 (2018).
doi: 10.1159/000490183
Habibi, A., Sadat Shandiz, S. A., Salehzadeh, A. & Moradi-Shoeili, Z. Novel pyridinecarboxaldehyde thiosemicarbazone conjugated magnetite nanoparticulates (MNPs) promote apoptosis in human lung cancer A549 cells. JBIC J. Biol. Inorg. Chem. 25, 13–22 (2020).
doi: 10.1007/s00775-019-01728-4
Ren, S. X. et al. Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer. Cancer Res. 72(24), 6512–6523 (2012).
doi: 10.1158/0008-5472.CAN-12-2359
Ren, S. X. et al. Correction: FK-16 derived from the anticancer peptide LL-37 induces caspase-independent apoptosis and autophagic cell death in colon cancer cells. PLoS One. 10(6), e0131750 (2015).
doi: 10.1371/journal.pone.0131750
Soares, N. D. C. P. et al. Lycopene extracts from different tomato-based food products induce apoptosis in cultured human primary prostate cancer cells and regulate TP53, Bax and Bcl-2 transcript expression. Asian Pac. J. Cancer Prev.: APJCP. 18(2), 339 (2017).