2. Academic Validation
  3. The Notch Inhibitors Isolated from Nerium indicum

The Notch Inhibitors Isolated from Nerium indicum

  • J Nat Prod. 2018 May 25;81(5):1235-1240. doi: 10.1021/acs.jnatprod.7b01031.
Midori A Arai 1,  Ryuta Akamine 1,  Narumi Hayashi 1,  Takashi Koyano 2,  Thaworn Kowithayakorn 3,  Masami Ishibashi 1
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences , Chiba University , 1-8-1 Inohana , Chuo-ku , Chiba 260-8675 , Japan.
  • 2 Temko Corporation , Tokyo 168-0062 , Japan.
  • 3 Faculty of Agriculture , Khon Kaen University , Khon Kaen 40002 , Thailand.
PMID: 29693393 DOI: 10.1021/acs.jnatprod.7b01031
Abstract

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.

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