Evodiamine Eliminates Colon Cancer Stem Cells via Suppressing Notch and Wnt Signaling

Molecules. 2019 Dec 10;24(24):4520. doi: 10.3390/molecules24244520.


Evodiamine, an alkaloid contained in traditional Asian herbal medicines that have been used for hundreds years, is interesting due to its cytotoxic effects against many cancers. We examined the effect of evodiamine on the cancer stem cell (CSC) population and the bulk cultured cancer cells (BCC) of colon cancers to examine the double targeting effect. We found that three colon cancer cell lines' BCC and CSC are effectively targeted by evodiamine. Evodiamine was able to suppress BCC proliferation and induce apoptosis of the cells captured in G2/M phase, as previously reported. However, evodiamine did not cause the accumulation of CSCs at a certain stage of the cell cycle, resulting in the elimination of stemness through an unknown mechanism. By analyzing the expression of 84 genes related to CSCs in two colon cancer cell lines' CSC, as well as performing further informatics analyses, and quantitative RT-PCR analyses of 24 CSC genes, we found that evodiamine suppressed the expression of the genes that control key signaling pathways of CSC, namely, WNT and NOTCH signaling, to lead CSC elimination. These results suggest that evodiamine should be further developed for targeting both BCCs and CSCs in colon cancers.

Keywords: WNT; cancer stem cell; colorectal cancer; evodiamine; notch.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Quinazolines / pharmacology*
  • Receptors, Notch / metabolism*
  • Signal Transduction / drug effects*
  • Wnt Proteins / metabolism*


  • Antineoplastic Agents
  • Quinazolines
  • Receptors, Notch
  • Wnt Proteins
  • evodiamine