Idarubicin HCl is an orally active anthracycline antileukemic agent [1]. Idarubicin HCl stabilizes the complex between topoisomerase II and DNA, preventing DNA repair and normal replication. This ultimately leads to accumulation of DNA breaks, replication arrest, and induction of cell cycle arrest and apoptosis [2-3]. Idarubicin HCl is primarily used to treat adult acute myeloid leukemia [4].
In T47D cells, the cell viability of cells was significantly reduced after Idarubicin HCl (0.1-10μM;24-72h) treatment [5]. In fibroblasts, Idarubicin HCl (0.5-10μM; 24h) induces a time-dependent decrease in mitochondrial membrane potential and significantly increases intracellular calcium concentration and caspase-3 activity [6].
In U937 cells xenograft mice model, combination of decitabine and Idarubicin HCl (0.5mg/kg; ip; 7d) effectively inhibits tumor growth [7]. In LNCaP cells xenograft mice model, Idarubicin HCl (0.25mg/kg; ip; 25d) alone or in combination with abiraterone acetate significantly reduced tumor growth and prolonged mouse survival [8].
References:
[1]. Orlandi P, Barbara C, Bocci G, et al. Idarubicin and idarubicinol effects on breast cancer multicellular spheroids[J]. Journal of chemotherapy, 2005, 17(6): 663-667.
[2]. Dartsch D C, Gieseler F. Repair of idarubicin-induced DNA damage: a cause of resistance?[J]. DNA repair, 2007, 6(11): 1618-1628.
[3]. van den Boogaard W M C, Komninos D S J, Vermeij W P. Chemotherapy side-effects: not all DNA damage is equal[J]. Cancers, 2022, 14(3): 627.
[4]. Sherif H A, Magdy A, Elshesheni H A, et al. Treatment outcome of doxorubicin versus idarubicin in adult acute myeloid leukemia[J]. Leukemia Research Reports, 2021, 16: 100272.
[5]. Zhong S, Li C, Han X, et al. Idarubicin stimulates cell cycle-and TET2-dependent oxidation of DNA 5-methylcytosine in cancer cells[J]. Chemical Research in Toxicology, 2019, 32(5): 861-868.
[6]. Dragojew S, Marczak A, Maszewski J, et al. The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts[J]. Cellular & molecular biology letters, 2008, 13(2): 182-194.
[7]. Li K, Hu C, Mei C, et al. Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target[J]. Journal of translational medicine, 2014, 12(1): 167.
[8]. Zhang Y, Wei W, Li C, et al. Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein[J]. Cell Death & Disease, 2022, 13(12): 1034.
Idarubicin HCl是一种口服蒽环类抗白血病药物 [1]。Idarubicin HCl能稳定拓扑异构酶II与DNA之间的复合物，从而阻止DNA修复和正常复制。这最终导致DNA断裂累积、复制停滞，并诱导细胞周期停滞和细胞凋亡 [2-3]。Idarubicin HCl主要用于治疗成人急性髓系白血病 [4]。
在T47D细胞中，Idarubicin HCl（0.1-10μM；24-72h）处理后，细胞活力显著降低 [5]。在成纤维细胞中，Idarubicin HCl（0.5-10μM；24h）诱导线粒体膜电位随时间依赖性下降，并显著增加细胞内钙离子浓度和胱天蛋白酶3活性 [6]。
在U937细胞异种移植小鼠模型中，decitabine与Idarubicin HCl（0.5mg/kg；ip；7d）联合应用可有效抑制肿瘤生长 [7]。在LNCaP细胞异种移植小鼠模型中，Idarubicin HCl（0.25mg/kg；ip；25d）单独使用或与abiraterone acetate联合使用可显著抑制肿瘤生长并延长小鼠生存期 [8]。