Effects of oral iron chelator deferasirox on human malignant lymphoma cells

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...

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Autores principales: Choi, Jong Gwon, Kim, Jung-Lim, Park, Joohee, Lee, Soonwook, Park, Seh Jong, Kim, Jun Suk, Choi, Chul Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464336/
https://www.ncbi.nlm.nih.gov/pubmed/23071474
http://dx.doi.org/10.5045/kjh.2012.47.3.194
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author Choi, Jong Gwon
Kim, Jung-Lim
Park, Joohee
Lee, Soonwook
Park, Seh Jong
Kim, Jun Suk
Choi, Chul Won
author_facet Choi, Jong Gwon
Kim, Jung-Lim
Park, Joohee
Lee, Soonwook
Park, Seh Jong
Kim, Jun Suk
Choi, Chul Won
author_sort Choi, Jong Gwon
collection PubMed
description 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 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. 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.
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spelling pubmed-34643362012-10-15 Effects of oral iron chelator deferasirox on human malignant lymphoma cells Choi, Jong Gwon Kim, Jung-Lim Park, Joohee Lee, Soonwook Park, Seh Jong Kim, Jun Suk Choi, Chul Won Korean J Hematol Original Article 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 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. 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. Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis 2012-09 2012-09-25 /pmc/articles/PMC3464336/ /pubmed/23071474 http://dx.doi.org/10.5045/kjh.2012.47.3.194 Text en © 2012 Korean Society of Hematology http://creativecommons.org/licenses/by-nc/3.0 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.
spellingShingle Original Article
Choi, Jong Gwon
Kim, Jung-Lim
Park, Joohee
Lee, Soonwook
Park, Seh Jong
Kim, Jun Suk
Choi, Chul Won
Effects of oral iron chelator deferasirox on human malignant lymphoma cells
title Effects of oral iron chelator deferasirox on human malignant lymphoma cells
title_full Effects of oral iron chelator deferasirox on human malignant lymphoma cells
title_fullStr Effects of oral iron chelator deferasirox on human malignant lymphoma cells
title_full_unstemmed Effects of oral iron chelator deferasirox on human malignant lymphoma cells
title_short Effects of oral iron chelator deferasirox on human malignant lymphoma cells
title_sort effects of oral iron chelator deferasirox on human malignant lymphoma cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464336/
https://www.ncbi.nlm.nih.gov/pubmed/23071474
http://dx.doi.org/10.5045/kjh.2012.47.3.194
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