Korean Journal of Pediatrics 2009;52(2):213-219.
Published online February 15, 2009.
Iron chelating agent, deferoxamine, induced apoptosis in Saos-2 osteosarcoma cancer cells
Eun Hye Park1, Hyo Jung Lee2, Soo Yeon Lee2, Sun Young Kim1, Ho Keun Yi3, Dae Yeol Lee2, Pyoung Han Hwang2
1Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju, Korea
2Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju, Korea
3Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju, Korea
Saos-2 골육종 세포에서 iron chelating agent, deferoxamine에 의한 apoptosis 유도
박은혜1, 이효정2, 이수연2, 김선영1, 이호근3, 이대열2, 황평한2
1전북대학교 의과대학 임상의학연구소
2전북대학교 의과대학 소아과학교실
3전북대학교 치과대학 생화학교실
Correspondence: 
Pyoung Han Hwang, Email: hwaph@chonbuk.ac.kr
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.
Key Words: Deferoxamine, Apoptosis, Signal pathway, Osteosarcoma


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