Narciclasine is a plant growth regulator with antimitotic activity and pro-apoptotic property [1]. Narciclasine can interact with the ribosomal 60S subunit and inhibit peptide bond formation by preventing the 3' end of the donor substrate from binding to the peptidyl transferase center, thereby reducing protein synthesis [2]. Narciclasine has been widely used to induce mitochondrial membrane potential depolarization and eliminate pathogenic parasites[3].
In vitro, Narciclasine treatment for 48 hours significantly inhibited the viability of HCT116, MDA-MB-231, and HT-29 cells with IC50 values of 0.108µM, 0.0495µM, and 1.205µM, respectively[4]. Treatment of SCC-47 cells with 100nM of Narciclasine for 24 hours resulted in decreased expression of the mesenchymal markers N-cadherin and β-catenin and inhibited cell migration and invasion[5]. Treatment of BCG-823 cells with 1µM of Narciclasine for 24 hours inhibited the proliferation of BCG-823 cells, inhibited the levels of p-AKT and p-mTOR, and promoted apoptosis and autophagy[6].
In vivo, Narciclasine treatment via oral administration at a dose of 1mg/kg/week for seven weeks attenuated high-fat diet-induced obesity in mice, reduced fat mass accumulation, and enhanced mitochondrial respiration and fatty acid oxidation in skeletal muscle[7]. Daily intraperitoneal injection of Narciclasine (1mg/kg/day) for 14 days reduced VEGF-induced angiogenesis in mice[8]. Subcutaneous administration of Narciclasine (1mg/kg) 12h prior to intraperitoneal injection of zymosan A attenuated inflammation and blocked leukocyte adhesion and transendothelial migration in a mouse model of zymosan-induced peritonitis[9].
References:
[1] Ingrassia L, Lefranc F, Dewelle J, et al. Structure− activity relationship analysis of novel derivatives of narciclasine (an Amaryllidaceae isocarbostyril derivative) as potential anticancer agents[J]. Journal of medicinal chemistry, 2009, 52(4): 1100-1114.
[2] Nair J J, van Staden J. Insight to the antifungal properties of Amaryllidaceae constituents[J]. Phytomedicine, 2020, 73: 152753.
[3] Gomes K S, Costa-Silva T A, Borges W S, et al. Antiparasitic Activity of Narciclasine and Evaluation of Its Effects on Plasma Membrane and Mitochondria of Trypanosoma cruzi[J]. ACS omega, 2025, 10(3): 3025-3032.
[4] Wang M, Liang L, Wang R, et al. Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells[J]. Natural Products and Bioprospecting, 2023, 13(1): 27.
[5] Shieu M K, Ho H Y, Lin C C, et al. Narciclasine suppresses oral cancer metastasis by modulating cathepsin B and extracellular signal–related kinase pathways[J]. Biomedicine & Pharmacotherapy, 2023, 158: 114159.
[6] Yuan Y, He X, Li X, et al. Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway[J]. BMC Pharmacology and Toxicology, 2021, 22(1): 70.
[7] Julien S G, Kim S Y, Brunmeir R, et al. Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle[J]. PLoS biology, 2017, 15(2): e1002597.
[8] Bräutigam J, Bischoff I, Schürmann C, et al. Narciclasine inhibits angiogenic processes by activation of Rho kinase and by downregulation of the VEGF receptor 2[J]. Journal of Molecular and Cellular Cardiology, 2019, 135: 97-108.
[9] Stark A, Schwenk R, Wack G, et al. Narciclasine exerts anti‐inflammatory actions by blocking leukocyte–endothelial cell interactions and down‐regulation of the endothelial TNF receptor 1[J]. The FASEB Journal, 2019, 33(8): 8771-8781.
Narciclasine是一种具有抗有丝分裂和促凋亡活性的植物生长调节剂[1]。Narciclasine可通过与核糖体60S亚基相互作用，抑制肽键形成从而减少蛋白质合成[2]。Narciclasine已广泛应用于诱导线粒体膜电位去极化以及清除致病性寄生虫[3]。
在体外，Narciclasine处理48小时能显著抑制HCT116、MDA-MB-231和HT-29细胞活力，IC50值分别为0.108µM、0.0495µM和1.205µM[4]。使用100nM的Narciclasine处理SCC-47细胞24小时，可降低间充质标志物N-钙黏蛋白和β-catenin的表达，并抑制细胞迁移和侵袭[5]。用1µM的Narciclasine处理BCG-823细胞24小时，能抑制细胞增殖，降低p-AKT和p-mTOR水平，并促进细胞凋亡和自噬[6]。
在体内，每周口服1mg/kg/week剂量的Narciclasine连续七周，可减轻高脂饮食诱导的小鼠肥胖，减少脂肪堆积，并增强骨骼肌线粒体呼吸和脂肪酸氧化[7]。每日腹腔注射1mg/kg/day剂量的Narciclasine连续14天，能抑制VEGF诱导的小鼠血管生成[8]。在zymosan A诱导的小鼠腹膜炎模型中，腹腔注射zymosan A前12小时皮下注射1mg/kg剂量的Narciclasine，可减轻炎症反应并阻断白细胞黏附和跨内皮迁移[9]。