Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

Biochem Biophys Res Commun. 2014 Jul 18;450(1):353-9. doi: 10.1016/j.bbrc.2014.05.110. Epub 2014 Jun 2.

Abstract

Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.

Keywords: Atractylenolide I; CD44; Cancer stem cells; Gastric cancer; Notch.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Lactones / pharmacology*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Receptors, Notch / metabolism*
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*

Substances

  • Lactones
  • Receptors, Notch
  • Sesquiterpenes
  • atractylenolide I