Korean J Hematol 2012; 47(3):
Published online September 25, 2012
https://doi.org/10.5045/kjh.2012.47.3.194
© The Korean Society of Hematology
1Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.
2Graduate School of Medicine, Korea University College of Medicine, Seoul, Korea.
Correspondence to : Correspondence to Chul Won Choi, M.D., Ph.D. Department of Internal Medicine, Korea University Guro Hospital, 97, Guro-dong-gil, Guro-gu, Seoul 152-703, Korea. Tel: +82-2-2626-3058, Fax: +82-2-862-4453, bonnie@korea.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Iron is essential for cell proliferation and viability. It has been reported that iron depletion by a chelator inhibits proliferation of some cancer cells. Deferasirox is a new oral iron chelator, and a few reports have described its effects on lymphoma cells. The goal of this study was to determine the anticancer effects of deferasirox in malignant lymphoma cell lines.
Three human malignant lymphoma cell lines (NCI H28:N78, Ramos, and Jiyoye) were treated with deferasirox at final concentrations of 20, 50, or 100 µM. Cell proliferation was evaluated by an MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. Western blot analysis was performed to determine the relative activity of various apoptotic pathways. The role of caspase in deferasirox-induced apoptosis was investigated using a luminescent assay.
The MTT assay showed that deferasirox had dose-dependent cytotoxic effects on all 3 cell lines. Cell cycle analysis showed that the sub-G1 portion increased in all 3 cell lines as the concentration of deferasirox increased. Early apoptosis was also confirmed in the treated cells by Annexin V and PI staining. Western blotting showed an increase in the cleavage of PARP, caspase 3/7, and caspase 9 in deferasirox-treated groups.
We demonstrated that deferasirox, a new oral iron-chelating agent, induced early apoptosis in human malignant lymphoma cells, and this apoptotic effect is dependent on the caspase-3/caspase-9 pathway.
Keywords Deferasirox, Malignant lymphoma, Apoptosis
Korean J Hematol 2012; 47(3): 194-201
Published online September 25, 2012 https://doi.org/10.5045/kjh.2012.47.3.194
Copyright © The Korean Society of Hematology.
Jong Gwon Choi1, Jung-Lim Kim2, Joohee Park1, Soonwook Lee1, Seh Jong Park1, Jun Suk Kim1, and Chul Won Choi1*
1Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.
2Graduate School of Medicine, Korea University College of Medicine, Seoul, Korea.
Correspondence to: Correspondence to Chul Won Choi, M.D., Ph.D. Department of Internal Medicine, Korea University Guro Hospital, 97, Guro-dong-gil, Guro-gu, Seoul 152-703, Korea. Tel: +82-2-2626-3058, Fax: +82-2-862-4453, bonnie@korea.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Iron is essential for cell proliferation and viability. It has been reported that iron depletion by a chelator inhibits proliferation of some cancer cells. Deferasirox is a new oral iron chelator, and a few reports have described its effects on lymphoma cells. The goal of this study was to determine the anticancer effects of deferasirox in malignant lymphoma cell lines.
Three human malignant lymphoma cell lines (NCI H28:N78, Ramos, and Jiyoye) were treated with deferasirox at final concentrations of 20, 50, or 100 µM. Cell proliferation was evaluated by an MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. Western blot analysis was performed to determine the relative activity of various apoptotic pathways. The role of caspase in deferasirox-induced apoptosis was investigated using a luminescent assay.
The MTT assay showed that deferasirox had dose-dependent cytotoxic effects on all 3 cell lines. Cell cycle analysis showed that the sub-G1 portion increased in all 3 cell lines as the concentration of deferasirox increased. Early apoptosis was also confirmed in the treated cells by Annexin V and PI staining. Western blotting showed an increase in the cleavage of PARP, caspase 3/7, and caspase 9 in deferasirox-treated groups.
We demonstrated that deferasirox, a new oral iron-chelating agent, induced early apoptosis in human malignant lymphoma cells, and this apoptotic effect is dependent on the caspase-3/caspase-9 pathway.
Keywords: Deferasirox, Malignant lymphoma, Apoptosis
MTT assay results show that deferasirox inhibited the proliferation of malignant lymphoma cell lines
Flow cytometry analysis results show that deferasirox treatment increased the percentage of cells in sub-G1 phase in a dose-dependent manner.
Deferasirox induces early apoptosis. Treatment with deferasirox caused dose-dependent apoptosis in 3 malignant lymphoma cell lines
Colorimetric assay results show that deferasirox treatment increased caspase-3/7 and caspase-9 activities. Caspase-3/7 and caspase-9 activities were measured after cells were treated with deferasirox for 24 h
Western blot analysis of apoptosis-related modulators. Expression of Bax and P53 was upregulated, whereas the expression of Bcl-2 was downregulated after malignant lymphoma cell lines were treated with deferasirox.
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MTT assay results show that deferasirox inhibited the proliferation of malignant lymphoma cell lines
Flow cytometry analysis results show that deferasirox treatment increased the percentage of cells in sub-G1 phase in a dose-dependent manner.
Deferasirox induces early apoptosis. Treatment with deferasirox caused dose-dependent apoptosis in 3 malignant lymphoma cell lines
Colorimetric assay results show that deferasirox treatment increased caspase-3/7 and caspase-9 activities. Caspase-3/7 and caspase-9 activities were measured after cells were treated with deferasirox for 24 h
Western blot analysis of apoptosis-related modulators. Expression of Bax and P53 was upregulated, whereas the expression of Bcl-2 was downregulated after malignant lymphoma cell lines were treated with deferasirox.