The Notch Inhibitors Isolated from Nerium indicum.
Midori A AraiRyuta AkamineNarumi HayashiTakashi KoyanoThaworn KowithayakornMasami IshibashiPublished in: Journal of natural products (2018)
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.
Keyphrases
- induced apoptosis
- signaling pathway
- cell proliferation
- cell cycle arrest
- endoplasmic reticulum stress
- pi k akt
- single cell
- high throughput
- cell death
- oxidative stress
- cell therapy
- stem cells
- wastewater treatment
- squamous cell carcinoma
- dna methylation
- mesenchymal stem cells
- bone marrow
- squamous cell
- protein protein
- bioinformatics analysis