Annonaceous acetogenins mediated up-regulation of Notch2 exerts growth inhibition in human gastric cancer cells<i>in vitro</i>

Abstract

// Yan Li 1 , Jianbin Ye 1 , Zhongbiao Chen 1 , Junjie Wen 1 , Fei Li 1 , Pengpeng Su 1 , Yanqing Lin 1 , Bingxin Hu 1 , Danlin Wu 1 , Lijun Ning 1 , Qi Xue 2 , Hongxiang Gu 2 , Yunshan Ning 1 1 School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, PR. China 2 Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR. China Correspondence to: Yunshan Ning, email: nys_liyan@sina.com Yan Li, email: luckyan@smu.edu.cn Keywords: annonaceous acetogenins, gastric cancer cell, Notch2, proliferation, apoptosis Received: December 22, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: February 08, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: February 18, 2017 ABSTRACT Background: 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&rsquo; activities in GC cells. Results: ACGs inhibited GC cells&rsquo; 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 Methods: 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. Conclusions: Up-regulation of Notch2 by ACGs is a potential therapeutic strategy for GC.