Deferasirox is an orally active iron chelator used to treat iron overload diseases[1]. Deferasirox belongs to the family of N-substituted bishydroxyphenyltriazole tridentate iron chelators with antitumor activity[2]. Deferasirox is a potent nuclear factor-κB (NF-κB) inhibitor whose mechanism of action is independent of chelation-induced cellular iron deprivation[3].
In vitro, treatment of esophageal cancer OE33, OE19, and OE21 cells with Deferasirox (20μM) for 48h significantly increased transferrin receptor 1 (TfR1) mRNA and protein expression in the three cell lines, resulting in decreased cell viability and proliferation[4]. Treatment of LX-2 stellate cells with Deferasirox (50μM) for 12h significantly reduced the expression of α1(I) procollagen and α-smooth muscle actin (αSMA)[5].
In vivo, oral administration of Deferasirox (20mg/kg) to mice with secondary iron overload (SIO) inoculated with L1210 cells prolonged survival, reduced tumor volume, and decreased iron content in liver or tumor tissues[6]. Oral administration of Deferasirox (25mg/kg) to rats with iron poisoning significantly improved serum biochemical parameters[7].
References:
[1] Choudhry V P, Naithani R. Current status of iron overload and chelation with deferasirox[J]. The Indian Journal of Pediatrics, 2007, 74: 759-764.
[2] Barani M, Sargazi S, Hajinezhad M R, et al. Preparation of pH-responsive vesicular deferasirox: Evidence from in silico, in vitro, and in vivo evaluations[J]. ACS omega, 2021, 6(37): 24218-24232.
[3] Messa E, Carturan S, Maffè C, et al. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging[J]. Haematologica, 2010, 95(8): 1308.
[4] Ford S J, Obeidy P, Lovejoy D B, et al. Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo[J]. British journal of pharmacology, 2013, 168(6): 1316-1328.
[5] Sobbe A, Bridle K R, Jaskowski L, et al. Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox[J]. Journal of Gastroenterology and Hepatology, 2015, 30(3): 638-645.
[6] Lee D H, Jang P S, Chung N G, et al. Deferasirox shows in vitro and in vivo antileukemic effects on murine leukemic cell lines regardless of iron status[J]. Experimental Hematology, 2013, 41(6): 539-546.
[7] Rahdar A, Hajinezhad M R, Sargazi S, et al. Biochemical effects of deferasirox and deferasirox-loaded nanomicellesin iron-intoxicated rats[J]. Life Sciences, 2021, 270: 119146.
Deferasirox是一种具口服活性的铁螯合剂，用于治疗铁过载疾病[1]。Deferasirox属于N取代的双羟基苯基三唑三齿铁螯合剂家族，具有抗肿瘤活性[2]。Deferasirox是一种有效的核因子-κB（NF-κB）抑制剂，其作用机制独立于螯合引起的细胞铁剥夺[3]。
在体外，Deferasirox（20μM）处理食管癌OE33、OE19、OE21细胞48h，显著增加了三种细胞系中转铁蛋白受体1（TfR1）mRNA和蛋白质表达，导致了细胞活力降低和增殖减少[4]。Deferasirox（50μM）处理LX-2星状细胞12h，显著降低了α1（I）前胶原和α-平滑肌肌动蛋白（αSMA）的表达[5]。
在体内，Deferasirox（20mg/kg）通过口服治疗接种L1210细胞的继发性铁过载（SIO）小鼠，延长了生存期，减小了肿瘤体积，降低了肝脏或肿瘤组织的铁含量[6]。Deferasirox（25mg/kg）通过口服治疗铁中毒大鼠，显著提高了大鼠的血清生化参数[7]。