N1-Acetylspermidine (hydrochloride) is an acetyl derivative of spermidine that acts as a substrate for polyamine oxidase (PAO)[1]. The level of N1-Acetylspermidine in tumor tissues has significantly increased, which acts as a novel biomarker of T-lymphoblastic lymphoma/acute leukemia (T-LBL/ALL) [2]. N1-Acetylspermidine has been used to examine the interaction between DNA and polyamines during the cleavage of phosphodiester bonds at apurinic/apyrimidinic sites in DNA[3].
In vitro, N1-Acetylspermidine treatment (100μM; 8h) increased the cell migration ability of HL-60 cells[4]. Treatment with 500µM N1-Acetylspermidine for 24 hours significantly induced apoptosis in SW620 cells in the presence of apple procyanidin[5].
In vivo, N1-Acetylspermidine was injected intraperitoneally once at a dose of 30mg/kg every three days for a total of 9 days, which significantly promoted the growth of liver cancer in mice with xenografted Hepa1-6 tumors[6].
References:
[1] Takao K, Sugita Y, Shirahata A. Assay of N1-acetylpolyamine oxidase activity with N1, N11-didansylnorspermine as the substrate by ion-pair reversed phase high performance liquid chromatography[J]. Biological and Pharmaceutical Bulletin, 2010, 33(7): 1089-1094.
[2] Liu Q, Zheng W, Yang Y, et al. Metabolomic Profiling Identifies Serum N1-Acetylspermidine As a Tumor-Specific Prognostic Biomarker for T-Lymphoblastic Lymphoma/Acute Leukemia[J]. Blood, 2024, 144: 5925.
[3] Haukanes B I, Szajko K, Helland D E. Action of spermidine, N1‐acetylspermidine, and N8acetylspermidine at apurinic sites in DNA[J]. FEBS letters, 1990, 269(2): 389-393.
[4] Kato M, Maeda K, Nakahara R, et al. Acidic extracellular pH drives accumulation of N1-acetylspermidine and recruitment of protumor neutrophils[J]. PNAS nexus, 2023, 2(10): pgad306.
[5] Gossé F, Roussi S, Guyot S, et al. Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells[J]. International journal of oncology, 2006, 29(2): 423-428.
[6] Liu Z Y, Wu C Y, Wu R Q, et al. Efflux of N1-acetylspermidine from hepatoma fosters macrophage-mediated immune suppression to dampen immunotherapeutic efficacy[J]. Immunity, 2025, 58(6): 1572-1585. e10.
N1-Acetylspermidine (hydrochloride)是亚精胺的一种乙酰化衍生物，可作为多胺氧化酶（PAO）的底物[1]。N1-Acetylspermidine在肿瘤组织中的水平显著升高，可作为T淋巴母细胞淋巴瘤/急性白血病（T-LBL/ALL）的新型生物标志物[2]。N1-Acetylspermidine已被用于研究DNA中脱嘌呤/脱嘧啶位点磷酸二酯键断裂过程中DNA与多胺之间的相互作用[3]。
在体外，使用100µM的N1-Acetylspermidine处理8小时，增强了HL-60细胞的迁移能力[4]。在苹果原花青素存在下，使用500µM的N1-Acetylspermidine处理24小时，显著诱导了SW620细胞凋亡[5]。
在体内，每隔三天腹腔注射一次N1-Acetylspermidine，剂量为30mg/kg，共计9天，显著促进了携带Hepa1-6肿瘤异种移植小鼠的肝癌生长[6]。