Anti-leukemic properties of deferasirox via apoptosis in murine leukemia cell lines

Sol-Rim Jeon; Jae-Wook Lee; Pil-Sang Jang; Nack-Gyun Chung; Bin Cho; Dae-Chul Jeong

doi:10.5045/br.2015.50.1.33

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Original Article

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Blood Res 2015; 50(1):

Published online March 31, 2015

https://doi.org/10.5045/br.2015.50.1.33

Anti-leukemic properties of deferasirox via apoptosis in murine leukemia cell lines

Sol-Rim Jeon, Jae-Wook Lee, Pil-Sang Jang, Nack-Gyun Chung^*, Bin Cho, and Dae-Chul Jeong

Author Info. +

Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Correspondence to : Correspondence to Nack-Gyun Chung, M.D., Ph.D. Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Korea. Tel: +82-2-2258-6188, Fax: +82-2-537-4544, cngped@catholic.ac.kr

Received: November 10, 2014; Revised: December 17, 2014; Accepted: February 5, 2015

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.

Abstract

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Abstract

Background

Although deferasirox (DFX) is reported to have anti-tumor effects, its anti-leukemic activity remains unclear. We evaluated the effect of DFX treatment on two murine lymphoid leukemia cell lines, and clarified the mechanisms underlying its potential anti-leukemic activity.

Methods

L1210 and A20 murine lymphoid leukemia cell lines were treated with DFX. Cell viability and apoptosis were evaluated by the 3-(4,5-dimethylthaizol-2-yl)-5-(3-carboxymethylphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and fluorescence-activated cell sorting (FACS) analysis, respectively. Immunoblotting was performed to detect the expression of key apoptotic proteins.

Results

In dose- and time-dependent manner, DFX decreased viability and increased apoptosis of murine leukemic cells. Fas expression was significantly higher in A20 cells than in L1210 cells at all DFX concentrations tested. Although both cell lines exhibited high caspase 3 and caspase 9 expression, a critical component of the intrinsic mitochondrial apoptotic pathway, expression was greater in L1210 cells. In contrast, caspase 8, a key factor in the extrinsic apoptotic pathway, showed greater expression in A20 cells. Cytochrome c expression was significantly higher in L1210 cells. In both cell lines, co-treatment with ferric chloride and DFX diminished the expression of these intracellular proteins, as compared to DFX treatment alone.

Conclusion

Treatment with DFX increased caspase-dependent apoptosis in two murine lymphoid leukemia cell lines, with differing apoptotic mechanisms in each cell line.

Keywords Lymphoid leukemia, Deferasirox, Apoptosis, Caspase

Article

Original Article

Blood Res 2015; 50(1): 33-39

Published online March 31, 2015 https://doi.org/10.5045/br.2015.50.1.33

Anti-leukemic properties of deferasirox via apoptosis in murine leukemia cell lines

Sol-Rim Jeon, Jae-Wook Lee, Pil-Sang Jang, Nack-Gyun Chung^*, Bin Cho, and Dae-Chul Jeong

Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Correspondence to: Correspondence to Nack-Gyun Chung, M.D., Ph.D. Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Korea. Tel: +82-2-2258-6188, Fax: +82-2-537-4544, cngped@catholic.ac.kr

Received: November 10, 2014; Revised: December 17, 2014; Accepted: February 5, 2015

Abstract

Background

Methods

Results

Conclusion

Treatment with DFX increased caspase-dependent apoptosis in two murine lymphoid leukemia cell lines, with differing apoptotic mechanisms in each cell line.

Keywords: Lymphoid leukemia, Deferasirox, Apoptosis, Caspase

Abstract

Fig 1.

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Figure 1.

Viability of L1210 (A, B) and A20 cells (C, D) after DFX treatment with or without FeCl₃, according to treatment time (24 vs. 48 hr) and DFX concentration (3.125-75 µM). Experiments were performed in triplicate. All data are presented as the mean±standard error (^a)P<0.05, ^b)P<0.01).

Blood Research 2015; 50: 33-39https://doi.org/10.5045/br.2015.50.1.33

Fig 2.

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Figure 2.

Measurement of apoptosis in L1210 (A, B) and A20 cells (C, D) after DFX treatment with or without FeCl₃, according to treatment time (24 vs. 48 hr) and DFX concentration (12.5-50 µM). Experiments were performed in triplicate. All data are presented as the mean±standard error (^a)P<0.05, ^b)P<0.01).

Blood Research 2015; 50: 33-39https://doi.org/10.5045/br.2015.50.1.33

Fig 3.

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Figure 3.

Measurement of CD95 (Fas) expression in L1210 and A20 cells after 24 h DFX treatment with or without FeCl₃, according to DFX concentration (12.5-50 µM). Experiments were performed in triplicate. All data are presented as the mean±standard error (^a)P<0.05, ^b)P<0.01).

Blood Research 2015; 50: 33-39https://doi.org/10.5045/br.2015.50.1.33

Fig 4.

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Figure 4.

Western blot measurement of caspase 3, caspase 9, caspase 8, PARP, and BAX expression in L1210 (A) and A20 cells (B) after treatment with 50 µM DFX with or without FeCl₃, according to treatment time (6-48 hr).

Blood Research 2015; 50: 33-39https://doi.org/10.5045/br.2015.50.1.33

Fig 5.

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Figure 5.

Western blot measurement of cytochrome c expression in L1210 (A) and A20 cells (B) after treatment with 50 µM DFX with or without FeCl₃, according to treatment time (6-48 hr).

Blood Research 2015; 50: 33-39https://doi.org/10.5045/br.2015.50.1.33