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

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.

Antitumor effects of the silencing of programmed cell death ligand�1 in colorectal cancer via immunoregulation

“…It has previously been demonstrated that PI3K/AKT signaling pathway can affect cell apoptosis through a variety of mechanisms, including promoting P53 nucleus translocation ( 28 , 31 ). In addition, PI3K/AKT can also modulate B cell lymphoma-2 associated agonist of cell death (Bad) activity, cause phosphorylation of caspase-9, block P53, and release apoptosis factors into the mitochondria ( 32 ). These mechanisms work together to block the process of programmed cell death, thus protecting the cells from apoptosis, promoting cell survival, and leading to the proliferation of tumor cells ( 33 ).…”

Natural Products to Fight Cancer: A Focus on Juglans regia

“…Juglanin demonstrated cytotoxicity on different models of breast (MCF-7, SKBR3, MDA-MB231 and BT474) [ 89 ], lung (A549, HCC827 and H1975) [ 90 ], and skin (UVB-stimulated B16F10) cancers. The fil rouge tracking juglanin’s antitumour potential is oxidative stress induction.…”

“…The fil rouge tracking juglanin’s antitumour potential is oxidative stress induction. Indeed, the juglanin-mediated ROS (reactive oxygen species) accumulation drove apoptosis and autophagy in lung and breast cancer cells [ 89 , 90 ]. In both cancer types, juglanin triggered both the extrinsic and intrinsic pathway of apoptosis.…”

“…The two cascades use different initiator caspases, such as caspase 8 for extrinsic or caspase 9 for intrinsic pathway, but they share common effector caspases (such as 3 and 7). Juglanin reduced the Bcl2/Bax ratio [ 89 , 90 ], activated caspases 3, 8 and 9 [ 89 ], and activated the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)/death receptors (DRs) relying on p53 activation [ 90 ]. The importance of triggering both pathways lies on the ability to promote apoptosis, even in the presence of defects in one of the two apoptotic machineries.…”

Cancer Metabolism and Autophagy

“…Hücrelerin tepken hücre türlerinden temizlenmesi Atg7 hasarlı tümör hücrelerinde besin yetersizliğinde hayatta kalmayı sağlamaz. Böylece otofaji hücrenin sağkalımını sağlamada yetersiz kalırken sisteme substrat sağlayarak redoks dengesini korumada görev almaktadır 21,22 .…”