Daunorubicin is a natural anthracycline antibiotic that intercalates into DNA double strands and inhibits topoisomerase II activity, thereby blocking DNA replication and transcription and inducing tumor cell apoptosis[1]. Clinically, Daunorubicin is primarily used for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)[2-3]. In addition, Daunorubicin has shown therapeutic potential against gliomas[4].
In vitro, treatment of human acute myeloid leukemia HL-60 cells with 0.1–1μM Daunorubicin for 1h, followed by incubation in drug-free medium for 6–24h, rapidly induces apoptotic cell death[5]. Exposure of human acute myeloid leukemia U937 cells to 0.5–1μM Daunorubicin for 2–24h significantly activates the PI3K/Akt signaling pathway, leading to cell cycle arrest and enhanced apoptosis[6].
In vivo, intraperitoneal administration of 2mg/kg Daunorubicin every other day for 15 days in HCT116 colorectal cancer xenograft BALB/c nude mice markedly inhibited tumor growth, reduced GLI1 expression in tumor tissues, and induced tumor cell apoptosis[7]. Intravenous tail-vein injection of 10mg/kg Daunorubicin for three consecutive days in C57BL/6 wild-type and Trp53-knockout mice elicited early, transient apoptosis in wild-type mice, with recovery to normal morphology by day 4. In contrast, Trp53-knockout mice exhibited delayed and persistent extensive necrosis and structural disruption despite the absence of early apoptosis[8].
References:
[1] Di Marco A, Cassinelli G, Arcamone F. The discovery of daunorubicin. Cancer Treat Rep. 1981;65 Suppl 4:3-8.
[2] Cann ML, Herring LE, Haar LL, et al. Dasatinib Is Preferentially Active in the Activated B-Cell Subtype of Diffuse Large B-Cell Lymphoma. J Proteome Res. 2019 Jan 4;18(1):522-534.
[3] Lin TY, Zhu Y, Li Y, et al. Daunorubicin-containing CLL1-targeting nanomicelles have anti-leukemia stem cell activity in acute myeloid leukemia. Nanomedicine. 2019 Aug;20:102004.
[4] Casazza AM, Pratesi G, Giuliani F, et al. Antileukemic activity of 4-demethoxydaunorubicin in mice. Tumori. 1980 Oct 31;66(5):549-64.
[5] Côme MG, Skladanowski A, Larsen AK, et al. Dual mechanism of daunorubicin-induced cell death in both sensitive and MDR-resistant HL-60 cells. Br J Cancer. 1999 Mar;79(7-8):1090-7.
[6] Plo I, Bettaïeb A, Payrastre B, et al. The phosphoinositide 3-kinase/Akt pathway is activated by daunorubicin in human acute myeloid leukemia cell lines. FEBS Lett. 1999 Jun 11;452(3):150-4.
[7] Kim BR, Kim DY, Tran NL, et al. Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines. Int J Oncol. 2024 Jun;64(6):66.
[8] Herfindal L, Myhren L, Gjertsen BT, et al. Functional p53 is required for rapid restoration of daunorubicin-induced lesions of the spleen. BMC Cancer. 2013 Jul 11;13:341.
Daunorubicin是一种天然来源的蒽环类抗生素，通过嵌入DNA双链并抑制拓扑异构酶Ⅱ活性，阻断DNA复制与转录，从而诱导肿瘤细胞凋亡[1]。临床上主要用于治疗急性髓系白血病（AML）和急性淋巴细胞白血病（ALL）[2-3]。此外，Daunorubicin还具备治疗神经胶质瘤等其他类型癌症的潜力[4]。
在体外，Daunorubicin（0.1–1μM）处理人急性髓系白血病HL-60细胞1h，随后在不含药物培养基中继续培养6–24h，可诱导快速细胞凋亡[5]。Daunorubicin（0.5–1μM）处理人急性髓系白血病U937细胞2–24h，可显著激活PI3K/Akt信号通路，诱导细胞周期阻滞并增强细胞凋亡[6]。
在体内，Daunorubicin（2mg/kg）腹腔注射于HCT116结直肠癌异种移植BALB/c裸鼠模型，隔日一次，持续15天，Daunorubicin显著抑制了肿瘤生长并降低肿瘤组织中GLI1表达水平，同时诱导肿瘤细胞凋亡[7]。Daunorubicin（10mg/kg）尾静脉注射于C57BL/6野生型与Trp53敲除小鼠，连续3天。Daunorubicin在野生型小鼠中引起早期、短暂的细胞凋亡，并在第4天恢复至正常形态；而在Trp53敲除小鼠中，尽管早期凋亡缺失，却于第4天出现延迟且持续的大面积坏死与结构紊乱[8]。