Astragalin-induced cell death is caspase-dependent and enhances the susceptibility of lung cancer cells to tumor necrosis factor by inhibiting the NF-κB pathway

// Minghui Chen 1, 2, * , Fangfang Cai 1, * , Daolong Zha 1 , Xueshi Wang 1 , Wenjing Zhang 2 , Yan He 2 , Qilai Huang 2, 3 , Hongqin Zhuang 1, 3 , Zi-Chun Hua 1, 2, 4 1 The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China 2 State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 3 Changzhou High-Tech Research Institute of Nanjing University and Target Pharma Laboratory, Changzhou, Jiangsu, China 4 College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China * These authors have contributed equally to this work Correspondence to: Zi-Chun Hua, email: hzc1117@nju.edu.cn Hongqin Zhuang, email: hqzhuang@nju.edu.cn Keywords: natural compounds, astragalin, apoptosis, non-small cell lung cancer, tumor therapy Received: June 13, 2016 Accepted: January 22, 2017 Published: February 10, 2017 ABSTRACT Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. Here, we demonstrate that the flavonoid astragalin (AG), also known as kaempferol-3-O-β-D-glucoside, induces cell death. This was prevented by the caspase inhibitors z-DEVD-FMK and z-LEHD-FMK. AG-induced cell death was associated with an increase in the Bax:Bcl-2 ratio and amplified by the inhibition of extracellular signal-regulated kinase (ERK)-1/2 and Akt signaling. Meanwhile, AG suppressed LPS-induced NF-κB activation. Additional studies revealed that AG inhibited tumor necrosis factor-alpha (TNFα)-induced NF-κB activity. AG also potentiated TNFα-induced apoptosis in A549 cells. Furthermore, using a mouse xenograft model, we demonstrated that AG suppressed tumor growth and induced cancer cell apoptosis in vivo . Taken together, these results suggest that AG may be a promising cancer therapeutic drug that warrants further investigation into its potential clinical applications.