The Notch Inhibitors Isolated from Nerium indicum

Midori A. Arai, Ryuta Akamine, Narumi Hayashi, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1235-1240
Number of pages6
JournalJournal of Natural Products
Volume81
Issue number5
DOIs
Publication statusPublished - 2018 May 25
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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  • Cite this

    Arai, M. A., Akamine, R., Hayashi, N., Koyano, T., Kowithayakorn, T., & Ishibashi, M. (2018). The Notch Inhibitors Isolated from Nerium indicum. Journal of Natural Products, 81(5), 1235-1240. https://doi.org/10.1021/acs.jnatprod.7b01031