Iron chelating agent, deferoxamine, induced apoptosis in Saos-2 osteosarcoma cancer cells.
10.3345/kjp.2009.52.2.213
- Author:
Eun Hye PARK
1
;
Hyo Jung LEE
;
Soo Yeon LEE
;
Sun Young KIM
;
Ho Keun YI
;
Dae Yeol LEE
;
Pyoung Han HWANG
Author Information
1. Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju, Korea.
- Publication Type:Original Article
- Keywords:
Deferoxamine;
Apoptosis;
Signal pathway;
Osteosarcoma
- MeSH:
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
- From:Korean Journal of Pediatrics
2009;52(2):213-219
- CountryRepublic of Korea
- Language:Korean
-
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.
