Alkaloids from nux vomica suppresses colon cancer cell growth through Wnt/β-catenin signaling pathway

Phytother Res. 2019 May;33(5):1570-1578. doi: 10.1002/ptr.6347. Epub 2019 Mar 24.

Abstract

Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/β-catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of β-catenin, c-Myc, and p-LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.

Keywords: Wnt/β-catenin signaling pathway; alkaloids; colon cancer; nux-vomica.

MeSH terms

  • Alkaloids / chemistry*
  • Animals
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Humans
  • Mice
  • Mice, Nude
  • Strychnine / analogs & derivatives*
  • Strychnine / chemistry*
  • Strychnos nux-vomica / chemistry*
  • Wnt Signaling Pathway / drug effects*

Substances

  • Alkaloids
  • brucine
  • Strychnine