Effects of oral iron chelator deferasirox on human malignant lymphoma cells.
10.5045/kjh.2012.47.3.194
- Author:
Jong Gwon CHOI
1
;
Jung Lim KIM
;
Joohee PARK
;
Soonwook LEE
;
Seh Jong PARK
;
Jun Suk KIM
;
Chul Won CHOI
Author Information
1. Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea. bonnie@korea.ac.kr
- Publication Type:Original Article
- Keywords:
Deferasirox;
Malignant lymphoma;
Apoptosis
- MeSH:
Annexin A5;
Apoptosis;
Benzoates;
Blotting, Western;
Caspase 9;
Cell Cycle;
Cell Line;
Cell Proliferation;
Flow Cytometry;
Humans;
Iron;
Lymphoma;
Triazoles
- From:Korean Journal of Hematology
2012;47(3):194-201
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: 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. METHODS: Three human malignant lymphoma cell lines (NCI H28:N78, Ramos, and Jiyoye) were treated with deferasirox at final concentrations of 20, 50, or 100 microM. 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. RESULTS: 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. CONCLUSION: 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.
