Juglanin inhibits lung cancer by regulation of apoptosis, ROS and autophagy induction

// Liang Chen 1 , Ya-Qiong Xiong 1 , Jing Xu 1 , Ji-Peng Wang 1 , Zi-Li Meng 1 and Yong-Qing Hong 1 1 Department of Respiration, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu 223300, China Correspondence to: Zi-Li Meng, email: mengziliha@qq.com Yong-Qing Hong, email: hongyongqingha@foxmail.com Keywords: juglanin, lung cancer, apoptosis, ROS, autophagy Received: June 27, 2017     Accepted: August 27, 2017     Published: September 28, 2017 ABSTRACT Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare , exerting suppressive activity against cancer cell progression in vitro and in vivo . Juglanin administration causes apoptosis and reactive oxygen species (ROS) in different types of cells through regulating various signaling pathways. In our study, the effects of juglanin on non-small cell lung cancer were investigated. A significant role of juglanin in suppressing lung cancer growth was observed. Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation. Anti-apoptotic members Bcl-2 and Bcl-xl were reduced, and pro-apoptotic members Bax and Bad were enhanced in cells and animals receiving juglanin. Additionally, nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) activation were inhibited by juglanin. Further, juglanin improved ROS and induced autophagy. ROS inhibitor N-acetyl-l-cysteine (NAC) reversed apoptosis induced by juglanin in cancer cells. The formation of autophagic vacoules and LC3/autophagy gene7 (ATG7)/Beclin1 (ATG6) over-expression were observed in juglanin-treated cells. Also, juglanin administration to mouse xenograft models inhibited lung cancer progression. Our study demonstrated that juglanin could be a promising candidate against human lung cancer progression.