acetogenins and Carcinogenesis

Gastric 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.. ACGs 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.. ACGs 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.. Up-regulation of Notch2 by ACGs is a potential therapeutic strategy for GC.

Topics: Acetogenins; Apoptosis; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA, Complementary; Flow Cytometry; G1 Phase Cell Cycle Checkpoints; Humans; Receptor, Notch2; RNA Interference; RNA, Small Interfering; Signal Transduction; Stomach Neoplasms; Transcription Factor HES-1; Transfection; Up-Regulation