The Antitumor Natural Compound Falcarindiol Disrupts Neural Stem Cell Homeostasis by Suppressing Notch Pathway

Int J Mol Sci. 2018 Nov 1;19(11):3432. doi: 10.3390/ijms19113432.

Abstract

Neural stem cells (NSCs) are undifferentiated, multi-potent cells that can give rise to functional neurons and glial cells. The disruption in NSC homeostasis and/or the impaired neurogenesis lead to diverse neurological diseases, including depression, dementia, and neurodegenerative disorders. Falcarindiol (FAD) is a polyacetylene found in many plants, and FAD shows the cytotoxicity against breast cancers and colon cancers. However, there is no research on the consequence of FAD treatment in normal stem cells. Here, we suggest that FAD has anticancer roles against glioblastoma cells by inducing the differentiation of glioblastoma stem-like cells, as well as activating apoptosis pathway in glioblastoma cells. On the other hand, we also show that FAD has detrimental effects by disrupting the maintenance of normal NSCs and altering the balance between self-renewal and differentiation of NSCs.

Keywords: Notch pathway; apoptosis; differentiation; falcarindiol; neural stem cell.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Biological Products / pharmacology*
  • Cell Differentiation
  • Cell Line, Tumor
  • Diynes / pharmacology*
  • Down-Regulation / drug effects
  • Fatty Alcohols / pharmacology*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Homeostasis*
  • Humans
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Receptors, Notch / metabolism*
  • Signal Transduction*

Substances

  • Antineoplastic Agents
  • Biological Products
  • Diynes
  • Fatty Alcohols
  • Receptors, Notch
  • falcarindiol