A novel LL-37@NH2@Fe3O4 inhibits the proliferation of the leukemia K562 cells: in-vitro study

Sci Rep. 2024 Sep 27;14(1):22245. doi: 10.1038/s41598-024-71946-7.

Abstract

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.

Keywords: Apoptosis; Bax; Bcl-2; K562 cells; NH2@LL-37@Fe3O4 nanoparticles; TP53.

MeSH terms

  • Antimicrobial Cationic Peptides* / chemistry
  • Antimicrobial Cationic Peptides* / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis* / drug effects
  • Cathelicidins*
  • Cell Proliferation* / drug effects
  • Cell Survival / drug effects
  • Humans
  • K562 Cells
  • Magnetic Iron Oxide Nanoparticles / chemistry
  • Magnetite Nanoparticles / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-bcl-2
  • Magnetite Nanoparticles
  • bcl-2-Associated X Protein
  • Antineoplastic Agents