Cytarabine (Ara-C) is a cytosine analog that primarily inhibits the function of DNA polymerase to block DNA synthesis[1]. Cytarabine is an antimetabolite and antitumor drug belonging to the anthracycline class of drugs, mainly used to treat acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and lymphoma[2]. Cytarabine can affect the cell cycle and cause S phase cell arrest[3].
In vitro, P493-6, PrEC-LHS, and RWPE cells were treated with Cytarabine (0-656µM) for 48h. P493-6 and PrEC-LHS cells only showed drug sensitivity when MYC (a transcription factor) levels were high, while RWPE cells showed no effect on MYC status[4]. Cytarabine (100, 500nM) was used to treat Kasumi-3 and U937 cells with knockdown of FHL1 expression for 72h, which had a significant cell killing effect[5].
In vivo, cytarabine (200 mg/kg) was administered intraperitoneally to treat acute myeloid leukemia model mice, which significantly increased the survival rate of mice from 20% to 59.3%. The residual leukemia cells after treatment showed chemoresistance[6]. Cytarabine (10 mg/kg) was injected intravenously to treat AML model mice, which significantly improved the survival rate of mice，combined with decitabine can enhance the therapeutic effect[7].
References:
[1] Zhuo M, Gorgun M F, Englander E W. Neurotoxicity of cytarabine (Ara-C) in dorsal root ganglion neurons originates from impediment of mtDNA synthesis and compromise of mitochondrial function[J]. Free Radical Biology and Medicine, 2018, 121: 9-19.
[2] Di Francia R, Crisci S, De Monaco A, et al. Response and toxicity to cytarabine therapy in leukemia and lymphoma: from dose puzzle to pharmacogenomic biomarkers[J]. Cancers, 2021, 13(5): 966.
[3] van Pelt K, de Haan G, Vellenga E, et al. Administration of low-dose cytarabine results in immediate S-phase arrest and subsequent activation of cell cycling in murine stem cells[J]. Experimental hematology, 2005, 33(2): 226-231.
[4] Chen W, Mou K Y, Solomon P, et al. Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy[J]. Proceedings of the National Academy of Sciences, 2021, 118(4): e2018861118.
[5] Fu Y, Xu M, Cui Z, et al. Genome-wide identification of FHL1 as a powerful prognostic candidate and potential therapeutic target in acute myeloid leukaemia[J]. EBioMedicine, 2020, 52.
[6] Mopin A, Leprêtre F, Sebda S, et al. Detection of residual and chemoresistant leukemic cells in an immune-competent mouse model of acute myeloid leukemia: Potential for unravelling their interactions with immunity[J]. Plos one, 2022, 17(4): e0267508.
[7] Jing Y, Jin X, Wang L, et al. Decitabine-based chemotherapy followed by haploidentical lymphocyte infusion improves the effectiveness in elderly patients with acute myeloid leukemia[J]. Oncotarget, 2017, 8(32): 53654.
Cytarabine（Ara-C）是一种胞嘧啶类似物，主要抑制DNA聚合酶的功能来阻断DNA合成[1]。Cytarabine是一种抗代谢药和抗肿瘤药，属于蒽环类药物，主要用于治疗急性髓系白血病（AML）、急性淋巴细胞白血病（ALL）和淋巴瘤[2]。Cytarabine能够影响细胞周期，可引起S期细胞阻滞[3]。
在体外，Cytarabine（0-656µM）处理P493-6、PrEC-LHS、RWPE细胞48h， P493-6和PrEC-LHS细胞仅在MYC（一种转录因子）水平较高的状态下产生药物敏感性，而RWPE细胞对Cytarabine的敏感性不受到MYC状态的影响[4]。Cytarabine（100、500nM）处理敲低了FHL1表达的Kasumi-3和U937细胞72h，具有显著的细胞杀伤作用[5]。
在体内，Cytarabine（200mg/kg）通过腹腔注射治疗急性髓系白血病（AML）模型小鼠，显著提高了小鼠的存活率，从20%提高至59.3%，治疗后残留的白血病细胞表现出了化学抗性[6]。Cytarabine（10mg/kg）通过静脉注射治疗AML模型小鼠，显著提高了小鼠的存活率，与地西他滨联合使用可以增强疗效[7]。