α-Chaconine-reduced Metastasis Involves a PI3K/Akt Signaling Pathway with Downregulation of NF-κB in Human Lung Adenocarcinoma A549 cells

2007 ◽  
Vol 55 (26) ◽  
pp. 11035-11043 ◽  
Author(s):  
Yuan-Wei Shih ◽  
Pin-Shern Chen ◽  
Cheng-Hsun Wu ◽  
Ya-Fang Jeng ◽  
Chau-Jong Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Human Lung ◽  
A549 Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Human Lung Adenocarcinoma ◽  
Lung Adenocarcinoma A549

20(S)-Protopanaxadiol Triggers Mitochondrial-Mediated Apoptosis in Human Lung Adenocarcinoma A549 Cells via Inhibiting the PI3K/Akt Signaling Pathway

2013 ◽  
Vol 41 (05) ◽  
pp. 1137-1152 ◽  
Author(s):  
Yun-Long Zhang ◽  
Rui Zhang ◽  
Hua-Li Xu ◽  
Xiao-Feng Yu ◽  
Shao-Chun Qu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Human Lung ◽  
A549 Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Human Lung Adenocarcinoma ◽  
Lung Adenocarcinoma A549 ◽  
Gsk 3Β ◽  
Induced Apoptosis

20(S)-Protopanaxadiol (PPD), an aglycone saponin ginsenoside isolated from Panax quinquefolium L, has been shown to inhibit the growth and proliferation in several cancer lines. However, the underlying molecular mechanisms remain poorly understood. In this study, we investigated the apoptosis-induced effects and the mechanism of 20(S)-PPD on human lung adenocarcinoma A549 cells. 20(S)-PPD showed a potent antiproliferative activity against A549 cells by triggering apoptosis. 20(S)-PPD-induced apoptosis was characterized by a dose-dependent loss of the mitochondrial membrane, release of cytochrome c, second mitochondria-derived activator of caspase (Smac) and apoptosis-inducing factor (AIF), activation of caspase-9/-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Caspase-dependence was indicated by the ability of the pan-caspase inhibitor z-VAD-fmk to attenuate 20(S)-PPD-induced apoptosis. After treatment with 20(S)-PPD, the proportion of A549 cells at the G0/G1 phase increased, while cells at the S and G2/M phases decreased. Furthermore, 20(S)-PPD also triggered down-regulation of phosphorylated Akt (Ser473/Thr308) and glycogen synthase kinase 3β (GSK 3β). Knockdown of GSK 3β with siRNA promoted the apoptotic effects of 20(S)-PPD. These results revealed an unexpected mechanism of action for this unique ginsenoside: triggering a mitochondrial-mediated, caspase-dependent apoptosis via down-regulation of the PI3K/Akt signaling pathway in A549 cells. Our findings encourage further studies of 20(S)-PPD as a promising chemopreventive agent against lung cancer.

scholarly journals Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

BioChem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 107-121
Author(s):  
Nghia Trong Vo ◽  
Eiichi Kusagawa ◽  
Kaori Nakano ◽  
Chihiro Moriwaki ◽  
Yasunobu Miyake ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Human Lung ◽  
A549 Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Human Lung Adenocarcinoma ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Lung Adenocarcinoma A549

Ostruthin (6-geranyl-7-hydroxycoumarin) is one of the constituents isolated from Paramignya trimera and has been classified as a simple coumarin. We recently reported the synthesis of alkyl triphenylphosphonium (TPP) derivatives from ostruthin and evaluated their anticancer activities. In the present study, we demonstrated that alkyl TPP ostruthin derivatives inhibited the up-regulation of cell-surface intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with tumor necrosis factor-α (TNF-α) without affecting cell viability, while ostruthin itself exerted cytotoxicity against A549 cells. The heptyl TPP ostruthin derivative (termed OS8) attenuated the up-regulation of ICAM-1 mRNA expression at concentrations higher than 40 µM in TNF-α-stimulated A549 cells. OS8 inhibited TNF-α-induced nuclear factor κB (NF-κB)-responsive luciferase reporter activity at concentrations higher than 40 µM, but did not affect the translocation of the NF-κB subunit RelA in response to the TNF-α stimulation at concentrations up to 100 µM. A chromatin immunoprecipitation assay showed that OS8 at 100 µM prevented the binding of RelA to the ICAM-1 promoter. We also showed that OS8 at 100 µM inhibited the TNF-α-induced phosphorylation of RelA at Ser 536. Moreover, the TNF-α-induced phosphorylation of an inhibitor of NF-κB α and extracellular signal-regulated kinase was reduced by OS8. These results indicate that OS8 has potential as an anti-inflammatory agent that targets the NF-κB signaling pathway.

Naphtho[1,2-b]furan-4,5-dione inactivates EGFR and PI3K/Akt signaling pathways in human lung adenocarcinoma A549 cells

Life Sciences ◽  
2010 ◽  
Vol 86 (5-6) ◽  
pp. 207-213 ◽  
Author(s):  
Jung-Chen Su ◽  
Kuei-Li Lin ◽  
Ching-Ming Chien ◽  
Chih-Hua Tseng ◽  
Yeh-Long Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
Human Lung ◽  
A549 Cells ◽  
Akt Signaling ◽  
Human Lung Adenocarcinoma ◽  
Lung Adenocarcinoma A549
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