Omer Ejlal A, Zhou Min, Roos Wynand P, Rashan Luay J, Fiebig Heinz-Herbert, Klauck Sabine M, Shan Letian, Efferth Thomas
Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, United States.
Phytomedicine. 2025 Nov;147:157173. doi: 10.1016/j.phymed.2025.157173. Epub 2025 Aug 15.
Non-small-cell lung cancer NSCLC is the major diagnosed type of lung cancers in the USA and Europe. It is generally related to poor prognosis and low rates of survival. Oleandrin is a cardiac glycoside occurring naturally in Nerium oleander (Apocynaceae).
To explore the potential therapeutic value of oleandrin against different cancer types with emphasis on NSCLC.
The effect of oleandrin in inhibiting the growth of different cancer cells was measured. In addition, oleandrin activity in inhibiting cell migration, suppression of MELK and inducing different modes of cell deaths were investigated using in silico, in vitro, and in vivo methods.
Oleandrin showed activity at low nanomolar level against 17 different types of cancer cells including NSCLC. Our investigations in A549 cells indicated that oleandrin is a MELK inhibitor, as it disrupted the microtubule network and inhibited migration of A549 cells. Moreover, it induced apoptosis, autophagy, and ferroptosis. Furthermore, our in vivo data revealed that oleandrin had significantly decreased tumor growth in a A549 xenograft zebrafish model in a dose-dependent manner. In silico analyses revealed that oleandrin bound to the ligand binding pocket with higher binding affinity than the known inhibitor MELK-8a. The binding was further confirmed in vitro using microscale thermophoresis. An ADMET (absorption, distribution, metabolism, excretion, toxicity) analysis, together with our in vivo toxicity studies and the previous clinical studies suggest that oleandrin has an acceptable safety profile.
Oleandrin could potentially have therapeutic effects for NSCLC patients and possibly for other cancer types.
非小细胞肺癌（NSCLC）是美国和欧洲诊断出的主要肺癌类型。它通常与预后不良和低生存率相关。夹竹桃苷是一种天然存在于夹竹桃（夹竹桃科）中的强心苷。
探讨夹竹桃苷对不同癌症类型，尤其是非小细胞肺癌的潜在治疗价值。
测定夹竹桃苷对不同癌细胞生长的抑制作用。此外，采用计算机模拟、体外和体内方法研究夹竹桃苷抑制细胞迁移、抑制MELK以及诱导不同细胞死亡模式的活性。
夹竹桃苷在低纳摩尔水平对包括非小细胞肺癌在内的17种不同类型的癌细胞显示出活性。我们在A549细胞中的研究表明，夹竹桃苷是一种MELK抑制剂，因为它破坏了微管网络并抑制了A549细胞的迁移。此外，它还诱导细胞凋亡、自噬和铁死亡。此外，我们的体内数据显示，夹竹桃苷在A549异种移植斑马鱼模型中以剂量依赖的方式显著降低了肿瘤生长。计算机模拟分析表明，夹竹桃苷与配体结合口袋结合，其结合亲和力高于已知抑制剂MELK-8a。使用微量热泳技术在体外进一步证实了这种结合。一项ADMET（吸收、分布、代谢、排泄、毒性）分析，以及我们的体内毒性研究和先前的临床研究表明，夹竹桃苷具有可接受的安全性。
夹竹桃苷可能对非小细胞肺癌患者以及其他癌症类型具有治疗作用。
