Notch signaling plays a crucial role in differentiation and cell maintenance, but once aberrantly activated, it contributes to cancer progression. Notch inhibitors were isolated from plant extracts and tested using an originally constructed cell-based assay system. We isolated eight compounds from Nerium indicum that showed inhibition of the Notch signaling pathway. HES1 and HES5 are target genes of the Notch signaling pathway, and oleandrin (1) decreased the protein levels of HES1 and HES5 in assay cells. Oleandrin (1) showed potent cytotoxicity against HPB-ALL cells and decreased HES1 and the Notch intracellular domain in these cells. The main mechanism of action of 1 appears to be inhibition of Notch signaling by acceleration of Notch intracellular domain degradation.

中文翻译：

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夹竹桃中的Notch抑制剂

Notch信号在分化和细胞维持中起着至关重要的作用，但是一旦异常激活，它就会促进癌症的发展。从植物提取物中分离Notch抑制剂，并使用最初构建的基于细胞的测定系统进行测试。我们从夹竹桃中分离了八种对Notch信号通路具有抑制作用的化合物。HES1和HES5是Notch信号通路的靶基因，夹竹桃苷（1）降低了测定细胞中HES1和HES5的蛋白质​​水平。夹竹桃苷（1）对HPB-ALL细胞显示出强大的细胞毒性，并降低了这些细胞中的HES1和Notch细胞内结构域。主要作用机理1 似乎是通过促进Notch细胞内结构域降解来抑制Notch信号传导。