title: Anti-leukemic properties of deferasirox via apoptosis in murine leukemia cell lines.
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.
  
  
  CONCLUSIONS
  Treatment with DFX increased caspase-dependent apoptosis in two murine lymphoid leukemia cell lines, with differing apoptotic mechanisms in each cell line.
authors.affiliation: Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sol-Rim
authors.initials: SR
authors.lastname: Jeon
authors.affiliation: Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Pil-Sang
authors.initials: PS
authors.lastname: Jang
authors.affiliation: Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Nack-Gyun
authors.initials: NG
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dae-Chul
authors.initials: DC
authors.lastname: Jeong
keywords: Apoptosis; Caspase; Deferasirox; Lymphoid leukemia
references.citation: Hematology Am Soc Hematol Educ Program. 2001;:47-61
references.pmid: 11722978
references.citation: Pediatr Blood Cancer. 2012 Aug;59(2):358-64
references.pmid: 22566388
references.citation: Anticancer Res. 2011 May;31(5):1741-4
references.pmid: 21617233
references.citation: Haematologica. 2010 Aug;95(8):1308-16
references.pmid: 20534700
references.citation: Leuk Res. 2007 Dec;31 Suppl 3:S16-22
references.pmid: 18037414
references.citation: Best Pract Res Clin Haematol. 2002 Jun;15(2):411-26
references.pmid: 12401315
references.citation: Eur J Pharmacol. 2008 Jul 28;589(1-3):1-7
references.pmid: 18619590
references.citation: Arch Pathol Lab Med. 2012 May;136(5):532-8
references.pmid: 22540302
references.citation: Cancer Sci. 2009 May;100(5):970-7
references.pmid: 19298223
references.citation: J Neurooncol. 2004 May;67(3):367-77
references.pmid: 15164994
references.citation: Clin Lymphoma Myeloma. 2009;9 Suppl 3:S305-11
references.pmid: 19778858
references.citation: J Infect Dis. 2000 Sep;182 Suppl 1:S115-21
references.pmid: 10944493
references.citation: Leuk Lymphoma. 2013 Apr;54(4):851-9
references.pmid: 23020673
references.citation: Korean J Hematol. 2012 Sep;47(3):194-201
references.pmid: 23071474
references.citation: Acta Haematol. 2011;126(4):241-5
references.pmid: 21951998
references.citation: J Clin Pharmacol. 2013 Sep;53(9):885-91
references.pmid: 23740857
references.citation: Exp Hematol. 2013 Jun;41(6):539-46
references.pmid: 23415674
references.citation: Blood. 2006 May 1;107(9):3436-41
references.pmid: 16627763
references.citation: Biometals. 2010 Apr;23(2):231-45
references.pmid: 19997770
references.citation: Blood. 1987 Mar;69(3):757-61
references.pmid: 3493042
references.citation: Haematologica. 2010 Jun;95(6):857-9
references.pmid: 20513804
references.citation: Eur Heart J. 2001 Dec;22(23):2171-9
references.pmid: 11913479
references.citation: Br J Pharmacol. 2013 Mar;168(6):1316-28
references.pmid: 23126308
references.citation: Cancer Res. 1989 Sep 1;49(17):4809-12
references.pmid: 2758414