Synergistic effect of magnetic nanoparticles of Fe(3)O(4) with gambogic acid on apoptosis of K562 leukemia cells

Int J Nanomedicine. 2009:4:251-9. doi: 10.2147/ijn.s7932.

Abstract

Gambogic acid (GA) has a significant anticancer effect on a wide variety of solid tumors. Recently, many nanoparticles have been introduced as drug-delivery systems to enhance the efficiency of anticancer drug delivery. The aim of this study was to investigate the potential benefit of combination therapy with GA and magnetic nanoparticles of Fe(3)O(4) (MNPs-Fe(3)O(4)). The proliferation of K562 cells and their cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscope and flow cytometry, respectively. Furthermore, real-time polymerase chain reaction and Western blotting analyses were performed to examine gene transcription and protein expression, respectively. The results showed that MNPs-Fe(3)O(4) dramatically enhanced GA-induced cytotoxicity and apoptosis in K562 cells. The typical morphological features of apoptosis treated with GA and MNPs-Fe(3)O(4) were observed under an optical microscope and a fluorescence microscope, respectively. The transcription of caspase-3 and bax gene in the group treated with GA and MNPs-Fe(3)O(4) was higher than that in the GA-alone group or MNPs-Fe(3)O(4)-alone group, but the transcription of bcl-2, nuclear factor-kappaB, and survivin degraded as did the expression of corresponding proteins in K562 cells. Our data suggests a potential clinical application of a combination of GA and MNPs-Fe(3)O(4) in leukemia therapy.

Keywords: K562 leukemia cells; apoptosis; gambogic acid; magnetic nanoparticles of Fe3O4; traditional Chinese medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects*
  • Dextrans / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Ferric Compounds / administration & dosage*
  • Ferrosoferric Oxide / administration & dosage*
  • Humans
  • K562 Cells
  • Magnetics
  • Magnetite Nanoparticles
  • Nanoparticles / administration & dosage*
  • Xanthones / administration & dosage*

Substances

  • Antineoplastic Agents
  • Dextrans
  • Ferric Compounds
  • Magnetite Nanoparticles
  • Xanthones
  • ferumoxtran-10
  • ferric oxide
  • gambogic acid
  • Ferrosoferric Oxide