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

被引:31
作者
Chen, Liang [1 ]
Xiong, Ya-Qiong [1 ]
Xu, Jing [1 ]
Wang, Ji-Peng [1 ]
Meng, Zi-Li [1 ]
Hong, Yong-Qing [1 ]
机构
[1] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Resp, Huaian 223300, Jiangsu, Peoples R China
关键词
juglanin; lung cancer; apoptosis; ROS; autophagy; NF-KAPPA-B; CELL-DEATH; MEDIATED ACTIVATION; EXPRESSION; JNK; AKT; PATHWAYS; IDENTIFICATION; SUPPRESSION; MODULATION;
D O I
10.18632/oncotarget.21317
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-kappa B (NF kappa B), 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.
引用
收藏
页码:93878 / 93898
页数:21
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