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.
Highlights
Lung cancer is reported as a leading cause for cancer death worldwide, accompanied with ascending incidence and mortality [1, 2]
Juglanin has been explored in human breast cancer development and progression through apoptosis and autophagy, which was related to intracellular reactive oxygen species (ROS) accumulation [13]
Juglanin induced cytotoxic effects and apoptosis in lung cancer cell lines The cytotoxicity of juglanin in lung cancer cell lines, and normal cells of MRC-5, was assessed through MTT assay
Summary
Lung cancer is reported as a leading cause for cancer death worldwide, accompanied with ascending incidence and mortality [1, 2]. Juglanin (C20H18O10, Figure 1), known as kaempferol 3-O-arabinofuranoside, is a kind of aldose reductase inhibitors [10, 11] It is isolated from the crude Polygonum aviculare, which has a potential value for different biological activities, such as antiwww.impactjournals.com/oncotarget inflammatory response and anti-tumor [12]. Juglanin has been explored in human breast cancer development and progression through apoptosis and autophagy, which was related to intracellular reactive oxygen species (ROS) accumulation [13]. Studies reported that juglanin could enhance autophagy and apoptosis in cancer cells in vitro and mouse xenograft models in vivo [14]. The study of juglanin used in NSCLC is little to be reported, and there might be new molecular mechanisms or signaling pathways by which juglanin affects the development of lung cancer
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