Korean J Pediatr.  2009 Feb;52(2):213-219. 10.3345/kjp.2009.52.2.213.

Iron chelating agent, deferoxamine, induced apoptosis in Saos-2 osteosarcoma cancer cells

• Park EH
• Lee HJ
• Lee SY
• Kim SY
• Yi HK
• Lee DY
• Hwang PH

• KMID: 2281678
• DOI: http://doi.org/10.3345/kjp.2009.52.2.213

Abstract

PURPOSE: Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism.
METHODS
To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis.
RESULTS
Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine.
CONCLUSION
These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

Keyword

Deferoxamine; Apoptosis; Signal pathway; Osteosarcoma

MeSH Terms

Apoptosis
Biological Processes
Blotting, Western
Caspase 3
Caspase 9
Cell Cycle
Cell Proliferation
Cell Survival
Deferoxamine
Diminazene
DNA Fragmentation
Electrons
Gentian Violet
Humans
Iron
Iron Chelating Agents
Iron Overload
Osteosarcoma
Oxygen
Proteins
Signal Transduction
Trypan Blue
Caspase 3
Caspase 9
Deferoxamine
Diminazene
Gentian Violet
Iron
Iron Chelating Agents
Oxygen
Proteins
Trypan Blue