Solasodine reverses stemness and epithelial-mesenchymal transition in human colorectal cancer

Biochem Biophys Res Commun. 2018 Oct 28;505(2):485-491. doi: 10.1016/j.bbrc.2018.09.094. Epub 2018 Sep 26.

Abstract

Adverse side effects of conventional chemotherapy, acquired resistance and fatal tumor metastasis of human colorectal cancer (CRC) are propelling the exploration for novel selective anticarcinogens. Solasodine is a main active component isolated from Solanum incanum L that exhibited a potent stemness and invasion inhibitory effect on human colorectal cancer HCT116 cells. Colony Spheroid formation assay showed that solasodine dose-dependently prohibited HCT116 cell stemness. CD133, CD44, Nanog, Oct-4 and Sox-2 were inhibited by solasodine to reverse stemness and similar mechanism was stimulated in vivo. Transwell and scratch wound assays revealed that solasodine impeded HCT116 cell invasion and migration potential strengthened by TGF-β1. Moreover, solasodine attenuated TGF-β1-induced EMT and decreased MMPs while in vivo study showed the same trend. The results of this study implied that solasodine may be a novel therapeutic drug for CRC treatment.

Keywords: Colorectal cancer; Epithelial-mesenchymal transition; Migration; Solasodine; Stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / genetics
  • Solanaceous Alkaloids / chemistry
  • Solanaceous Alkaloids / pharmacology*
  • Solanaceous Alkaloids / therapeutic use
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Antineoplastic Agents
  • Solanaceous Alkaloids
  • Transforming Growth Factor beta1
  • solasodine