Solasodine inhibits human colorectal cancer cells through suppression of the AKT/glycogen synthase kinase-3β/β-catenin pathway

Cancer Sci. 2017 Nov;108(11):2248-2264. doi: 10.1111/cas.13354. Epub 2017 Sep 14.

Abstract

Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti-oxidant, anti-infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The results show that solasodine prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating MMPs. Solasodine was also found to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis. When cells were pretreated with AKT activator (insulin-like growth factor-1) followed by solasodine, the solasodine-induced apoptosis was partially abrogated by insulin-like growth factor-1. Moreover, solasodine hindered tumor development and stimulated similar mechanisms in vivo. In general, our study provides the first evidence that solasodine has a suppressive effect on CRC cells and that this agent may be a novel therapeutic drug for CRC treatment.

Keywords: Apoptosis; colorectal cancer; metastasis; solasodine; β-Catenin.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycogen Synthase Kinase 3 beta / genetics
  • Humans
  • Insulin-Like Growth Factor I / administration & dosage*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Signal Transduction / drug effects
  • Solanaceous Alkaloids / administration & dosage*
  • bcl-2-Associated X Protein / genetics

Substances

  • BAX protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Solanaceous Alkaloids
  • bcl-2-Associated X Protein
  • Insulin-Like Growth Factor I
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • solasodine