Fractionated ionizing radiation facilitates interferon‐γ signaling and anticancer activity in lung adenocarcinoma cells

2019 ◽  
Vol 234 (9) ◽  
pp. 16003-16010 ◽  
Author(s):  
Szu‐Yuan Wu ◽  
Chia‐Ling Chen ◽  
Po‐Chun Tseng ◽  
Chi‐Yun Chiu ◽  
Yung‐En Lin ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Interferon Γ ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

scholarly journals ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

2018 ◽  
Vol 45 (3) ◽  
pp. 917-934 ◽  
Author(s):  
Fangqiong Li ◽  
Dongxiao Zhao ◽  
Suwen Yang ◽  
Juan Wang ◽  
Qin Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
A549 Lung

Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatography-mass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.

scholarly journals Santamarine Inhibits NF-κB Activation and Induces Mitochondrial Apoptosis in A549 Lung Adenocarcinoma Cells via Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xuefeng Wu ◽  
Hua Zhu ◽  
Jingzhe Yan ◽  
Muhammad Khan ◽  
Xiuyan Yu
Keyword(s):  
Oxidative Stress ◽  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Molecular Mechanism ◽  
Dependent Manner ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
A549 Lung

Santamarine (STM), a sesquiterpene lactone component of Magnolia grandiflora and Ambrosia confertiflora, has been shown to possess antimicrobial, antifungal, antibacterial, anti-inflammatory, and anticancer activities. However, no study has yet been conducted to investigate the molecular mechanism of STM-mediated anticancer activity. In the present study, we found that STM inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells through induction of oxidative stress. STM induces oxidative stress by promoting reactive oxygen species (ROS) generation, depleting intracellular glutathione (GSH), and inhibiting thioredoxin reductase (TrxR) activity in a dose-dependent manner. Further mechanistic study demonstrated that STM induces apoptosis by modulation of Bax/Bcl-2 expressions, disruption of mitochondrial membrane potential, activation of caspase-3, and cleavage of PARP in a dose-dependent manner. Moreover, STM inhibited the constitutive and inducible translocation of NF-κBp65 into the nucleus. IKK-16 (I-κB kinase inhibitor) augmented the STM-induced apoptosis, indicating that STM induces apoptosis in A549 cells at least in part through NF-κB inhibition. Finally, STM-induced apoptosis and expressions of apoptosis regulators were effectively inhibited by thiol antioxidant N-acetyl-L-cysteine (NAC), indicating that STM exerts its anticancer effects mainly through oxidative stress. To the best of our knowledge, this is the first report providing evidence of anticancer activity and molecular mechanism of STM.

scholarly journals Proscillaridin A Promotes Oxidative Stress and ER Stress, Inhibits STAT3 Activation, and Induces Apoptosis in A549 Lung Adenocarcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Amara Maryam ◽  
Tahir Mehmood ◽  
Qiulong Yan ◽  
Yongming Li ◽  
Muhammad Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Adenocarcinoma ◽  
Er Stress ◽  
Anticancer Activity ◽  
Sh2 Domain ◽  
Ros Generation ◽  
Proscillaridin A ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
A549 Lung

Cardiac glycosides are natural compounds used for the treatment of cardiovascular disorders. Although originally prescribed for cardiovascular diseases, more recently, they have been rediscovered for their potential use in the treatment of cancer. Proscillaridin A (PSD-A), a cardiac glycoside component of Urginea maritima, has been reported to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSD-A in various cancers including lung cancer remain largely unexplored. In the present study, we found that PSD-A inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells. The anticancer activity of PSD-A was found to be associated with the activation of JNK, induction of ER stress, mitochondrial dysfunction, and inhibition of STAT3 activation. PSD-A induces oxidative stress as evidenced from ROS generation, GSH depletion, and decreased activity of TrxR1. PSD-A-mediated ER stress was verified by increased phosphorylation of eIF2α and expression of its downstream effector proteins ATF4, CHOP, and caspases-4. PSD-A triggered apoptosis by inducing JNK (1/2) activation, increasing bax/bcl-2 ratio, dissipating mitochondrial membrane potential, and inducing cleavage of caspases and PARP. Further study revealed that PSD-A inhibits both constitutive and inducible STAT3 activations and decreases STAT3 DNA-binding activity. Moreover, PSD-A-mediated inhibition of STAT3 activation was found to be associated with increased SHP-1 expression, decreased phosphorylation of Src, and binding of PSD-A with STAT3 SH2 domain. Finally, STAT3 knockdown by shRNA inhibited growth and enhanced apoptotic efficacy of PSD-A. Taken together, the data suggest that PSD-A could be developed into a potential therapeutic agent against lung adenocarcinoma.

Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells

2016 ◽  
Vol 37 ◽  
pp. 148-161 ◽  
Author(s):  
Malgorzata Kucinska ◽  
Hanna Piotrowska-Kempisty ◽  
Natalia Lisiak ◽  
Mariusz Kaczmarek ◽  
Hanna Dams-Kozlowska ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Human Lung ◽  
The Novel ◽  
Human Lung Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

scholarly journals Regulation of VEGF-expression by patupilone and ionizing radiation in lung adenocarcinoma cells

Lung Cancer ◽  
2011 ◽  
Vol 73 (3) ◽  
pp. 294-301 ◽  
Author(s):  
Carla Rohrer Bley ◽  
Katrin Orlowski ◽  
Polina Furmanova ◽  
Paul M.J. McSheehy ◽  
Martin Pruschy
Keyword(s):  
Ionizing Radiation ◽  
Lung Adenocarcinoma ◽  
Vegf Expression ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

scholarly journals Radioresistant human lung adenocarcinoma cells that survived multiple fractions of ionizing radiation are sensitive to HSP90 inhibition

Oncotarget ◽  
2015 ◽  
Vol 6 (42) ◽  
pp. 44306-44322 ◽  
Author(s):  
Roberto Gomez-Casal ◽  
Michael W. Epperly ◽  
Hong Wang ◽  
David A. Proia ◽  
Joel S. Greenberger ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Lung Adenocarcinoma ◽  
Human Lung ◽  
Hsp90 Inhibition ◽  
Human Lung Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells
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