Annonaceous acetogenins mediated up-regulation of Notch2 exerts growth inhibition in human gastric cancer cellsin vitro

Abstract

BackgroundGastric cancer (GC) is a global health problem because of limited treatments and poor prognosis. Annonaceous acetogenins (ACGs) has been reported to exert anti-tumorigenic effects in cancer, yet the mechanism underlying its effects on GC remains largely unknown. Notch signaling plays a critical role in cell proliferation, differentiation and apoptosis. Therefore, it may contribute to the development of GC. This study aims to explore the role of Notch2 in ACGs’ activities in GC cells.ResultsACGs inhibited GC cells’ viability in a dose dependent manner and led to cell apoptosis and cell cycle arrest in G0/G1 phase with an increased Notch2 expression. Additionally, Notch2 siRNA reduced ACGs-induced cell growth inhibition while Notch2 cDNA transfection did the opposite.Materials and MethodsACGs were administrated in GC cells and cell proliferation was assayed by MTS, cell apoptosis and cell cycle were detected by flow cytometry. Additionally, the expression of Notch2 and the downstream target Hes1 were identified by Western blot. Furthermore, Notch2-siRNA transfection and Notch2-cDNA were performed to investigate the role of Notch2 in the antitumor effect of ACGs. Conclusions: Up-regulation of Notch2 by ACGs is a potential therapeutic strategy for GC.

ILF3 promotes gastric cancer proliferation and may be used as a prognostic marker

“…GC is one of the most common cancers in China, with high mortality due to its aggressiveness, and poor prognosis (11–13). Although a number of genes and signaling pathways involved in GC development have been identified (14–17), the mechanism is still too sophisticated to be fully understood. Identifying novel genes closely associated with GC development is clinically necessary.…”

The future potential of Annona muricata L. extract and its bioactive compounds as radiation sensitizing agent: proposed mechanisms based on a systematic review

“…Besides that, we also found distinct findings amongst different authors. Inhibition at the G2-M phase was reported by Magadi (20,38,46,49,54,56,58). Neither of these two contrasting observations might be wrong, as they perform different observations in different cell lines.…”

The function of Notch1 intracellular domain in the differentiation of gastric cancer

“…Convincing evidence indicated that Notch1 and NICD was highly expressed in the AGS cell line ( 10 , 44 ). An additional study indicated that there was no significant difference between the levels of Notch2 in the normal gastric epithelial AGS and GES-1 cell lines ( 45 ). For Notch3 and Notch4, there have been no studies that have observed a difference in Notch3 or Notch4 expression between the AGS cell line and normal gastric cells.…”