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 Size dependent anti-invasiveness of silver nanoparticles in lung cancer cells

RSC Advances ◽  
2019 ◽  
Vol 9 (37) ◽  
pp. 21134-21138 ◽  
Author(s):  
Yu Mei Que ◽  
Xiao Qing Fan ◽  
Xiao Juan Lin ◽  
Xiao Li Jiang ◽  
Ping Ping Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Silver Nanoparticles ◽  
Cancer Cells ◽  
Elevated Level ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Size Dependent ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
A549 Lung

Size-dependent anti-invasiveness effect of AgNPs was determined using A549 lung adenocarcinoma cells. The 13 nm AgNPs can significantly inhibit the migration and invasion of A549 cells and induce the elevated level of ROS and NF-κB directed cell apoptosis.

Role of DACH1 on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Junjie Yu ◽  
Ping Jiang ◽  
Ke Zhao ◽  
Zhiguo Chen ◽  
Tao Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Human Lung ◽  
A549 Cells ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Objective: To investigate DACH1 protein expression in lung cancer tissue and matched paracancerous tissue, and explore its effect on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells (HLACs). Methods: Tumor tissue and matched paracancerous tissue was collected from 46 patients with pathologically diagnosed lung cancer. RT-PCR was perfomed to detect DACH1 mRNA expression and immunohistochemistry to measured DACH1 protein expression. To determine the effect of DACH1 on lung cancer behavior, small interfering RNA (siRNA) was used to silence DACH1 expression in A549 cells. The impact on the proliferation of tumor cells was then observed by MTT assay, changes in the invasion of tumor cells were identified using transwell chamber assay, and the effects on apoptosis in the cell line were detected using flow cytometry. Results: The expression of DACH1 mRNA and DACH1 protein were significantly decreased in lung cancer tissue versus matched paracancerous control tissue. Silencing of DACH1 expression in A549 cells significantly enhanced cell proliferation, significantly increased cell invasion and significantly reduced spontaneous apoptosis. Conclusion: DACH1 is downregulated in lung adenocarcinoma tissue. In vitro assessment shows that DACH1 functions as a tumor suppressor, suggesting its potential use as new target for lung cancer treatment.

scholarly journals Myrcene Exhibits Antitumor Activity Against Lung Cancer Cells by Inducing Oxidative Stress and Apoptosis Mechanisms

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2096118
Author(s):  
Xudong Bai ◽  
Jin Tang
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Cancer Cells ◽  
Metabolic Activity ◽  
Lung Cancer Cells ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
A549 Lung

Myrcene, a natural olefinic hydrocarbon, possesses anti-inflammatory, analgesic, antibiotic, and antimutagenic properties, but its anticancer effect has not yet been elucidated. Hence, the present study was framed to investigate the molecular mechanism by which myrcene mediates the anticancer activity of A549 lung adenocarcinoma cells. In vitro, A549 lung cancer cells were cultured either with or without myrcene, and the effects on cellular metabolic activity, levels of reactive oxygen species (ROS), mitochondrial integrity, deoxyribonucleic acid (DNA) damage, and activity of caspases were analyzed. The study demonstrated that compared with control cells, myrcene induces cell death in a dose-dependent manner while inducing ROS levels. Further experiments revealed that the metabolic activity of the A549 lung adenocarcinoma cells was diminished with increased DNA damage and altered cellular integrity. In addition, increased activity of caspase-3 was also evidenced with reduced mitochondrial membrane potential synthesis in the myrcene-treated cells, which demonstrate that lung cancer cells experience signs of toxicity during myrcene treatment through the activation of the apoptosis mechanism via mitochondria-mediated cell death signaling and induction of oxidative stress. The results provide the first report on the evidence of anticancer activity and the possibility of a new drug that could be used for the treatment of lung cancer.

scholarly journals Dicentrine Potentiates TNF-α-Induced Apoptosis and Suppresses Invasion of A549 Lung Adenocarcinoma Cells via Modulation of NF-κB and AP-1 Activation

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4100 ◽  
Author(s):  
Chanatip Ooppachai ◽  
Pornngarm Limtrakul (Dejkriengkraikul) ◽  
Supachai Yodkeeree
Keyword(s):  
Lung Adenocarcinoma ◽  
Transcriptional Activity ◽  
A549 Cells ◽  
Anticancer Activities ◽  
Necrosis Factor Alpha ◽  
Adenocarcinoma Cells ◽  
Tnf Α ◽  
Lung Adenocarcinoma Cells ◽  
Induced Apoptosis ◽  
A549 Lung

Numerous studies have indicated that tumor necrosis factor-alpha (TNF-α) could induce cancer cell survival and metastasis via activation of transcriptional activity of NF-κB and AP-1. Therefore, the inhibition of TNF-α-induced NF-κB and AP-1 activity has been considered in the search for drugs that could effectively treat cancer. Dicentrine, an aporphinic alkaloid, exerts anti-inflammatory and anticancer activities. Therefore, we investigated the effects of dicentrine on TNF-α-induced tumor progression in A549 lung adenocarcinoma cells. Our results demonstrated that dicentrine effectively sensitizes TNF-α-induced apoptosis in A549 cells when compared with dicentrine alone. In addition, dicentrine increases caspase-8, -9, -3, and poly (ADP-ribose) polymerase (PARP) activities by upregulating the death-inducing signaling complex and by inhibiting the expression of antiapoptotic proteins including cIAP2, cFLIP, and Bcl-XL. Furthermore, dicentrine inhibits the TNF-α-induced A549 cells invasion and migration. This inhibition is correlated with the suppression of invasive proteins in the presence of dicentrine. Moreover, dicentrine significantly blockes TNF-α-activated TAK1, p38, JNK, and Akt, leading to reduced levels of the transcriptional activity of NF-κB and AP-1. Taken together, our results suggest that dicentrine could enhance TNF-α-induced A549 cell death by inducing apoptosis and reducing cell invasion due to, at least in part, the suppression of TAK-1, MAPK, Akt, AP-1, and NF-κB signaling pathways.

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.

ERGIC3 Silencing Additively Enhances the Growth Inhibition of BFA on Lung Adenocarcinoma Cells

2020 ◽  
Vol 20 (1) ◽  
pp. 67-75
Author(s):  
Qiurong Zhao ◽  
Mingsong Wu ◽  
Xiang Zheng ◽  
Lei Yang ◽  
Zhimin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Golgi Body ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth

Background: Brefeldin A (BFA) has been known to induce endoplasmic reticulum stress (ERS) and Golgi body stress in cancer cells. ERGIC3 (endoplasmic reticulum-Golgi intermediate compartment 3) is a type II transmembrane protein located in the endoplasmic reticulum and Golgi body. ERGIC3 over-expression is frequently observed in cancer cells. Objective: In this study, we aim to explore whether BFA administered concurrently with ERGIC3 silencing would work additively or synergistically inhibit cancer cell growth. Methods: ERGIC3-siRNA was used to knock-down the expression of ERGIC3 and BFA was used to induce ERS in lung cancer cell lines GLC-82 and A549. Q-RT-PCR and Western Blot analysis were used to detect the expression of ERGIC3 and downstream molecules. GraphPad Prism 6 was used to quantify the data. Results: We demonstrated that silencing of ERGIC3 via siRNA effectively led to down-regulation of ERGIC3 at both mRNA and protein levels in GLC-82 and A549 cells. While BFA or ERGIC3- silencing alone could induce ERS and inhibit cell growth, the combination treatment of lung cancer cells with ERGIC3-silencing and BFA was able to additively enhance the inhibition effects of cell growth through up-regulation of GRP78 resulting in cell cycle arrest. Conclusion: ERGIC3 silencing in combination with BFA treatment could additively inhibit lung cancer cell growth. This finding might shed a light on new adjuvant therapy for lung adenocarcinoma.

scholarly journals BSCI-16. HEMODYNAMIC SHEAR STRESS SELECTS A SUBPOPULATION OF LUNG ADENOCARCINOMA CELLS WITH HIGHER METASTATIC CAPACITY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i4-i4
Author(s):  
Keila N Alvarado-Estrada ◽  
Lina Marenco-Hillembrand ◽  
David Mampre ◽  
Alfredo Quinones-Hinojosa ◽  
Rachel Sarabia-Estrada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Shear Stress ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Survival Data ◽  
Metastatic Spread ◽  
Adenocarcinoma Cells ◽  
Metastatic Capacity ◽  
Lung Adenocarcinoma Cells ◽  
Hemodynamic Shear Stress

Abstract Patients with primary cancers often develop delayed brain metastases. One of the most common cancer types and sources of brain metastasis is lung cancer. For metastasis from lung cancer the 3-year survival is < 5%. Cancer cells in circulation are responsible for metastatic spread. The mechanical microenvironment plays an important role in cancer cells behavior. When cancer cells reach the bloodstream they are exposed to hemodynamic shear stress. It has been shown that most of the circulating tumor cells die once they reach the bloodstream, but the biology of the survival cells is poorly understood. We designed a microfluidics system that simulated the mechanical stress in the human circulating system such as turbulence, change in pressure (0.4-15dyn/cm2) and flow rate (1.06–106.1mm/s). Lung adenocarcinoma cells (A549) were put into circulation and collected after 72 hours. It was found that, 1.4±0.3% of the cells survived, and viability was evaluated by LDH and calcein. CD133, SOX2, and NANOG were downregulated and EMT genes were upregulated in the circulating cancer cells (CCCs) compared with cells in static-suspension or 2D. After re-seeding in 2D, CCCs overexpressed CD133. Female athymic nude rats (6-8weeks,n=16) received intracardiac injections of CCCs or 2D cells (GFP-LUC lentivirus traduced). Bioluminescence imaging was performed every week; the survival in of the CCCs group was lower than the 2D group. One-way ANOVA test was used to analyze survival and gene expression. Survival data was plotted on a Kaplan-Meier curve and compared using the Mantel-Cox logrank test, p=< 0.05. We have isolated a cellular subpopulation of lung adenocarcinoma with high resistance to hemodynamic shear stress that shows a higher metastatic capacity and genetic plasticity compared with cells growing in suspension or 2D. Targeting these cells would potentially allow us to develop personalized treatments to help to stop metastatic spread and improve actual therapeutical strategies.

scholarly journals Activation of Mitochondrial 2-Oxoglutarate Dehydrogenase by Cocarboxylase in Human Lung Adenocarcinoma Cells A549 Is p53/p21-Dependent and Impairs Cellular Redox State, Mimicking the Cisplatin Action

2020 ◽  
Vol 21 (11) ◽  
pp. 3759
Author(s):  
Victoria I. Bunik ◽  
Vasily A. Aleshin ◽  
Xiaoshan Zhou ◽  
Vyacheslav Yu. Tabakov ◽  
Anna Karlsson
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Redox State ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
A549 Cells ◽  
Specific Inhibitor ◽  
Adenocarcinoma Cells ◽  
Oxoglutarate Dehydrogenase ◽  
Lung Adenocarcinoma Cells

Genetic up-regulation of mitochondrial 2-oxoglutarate dehydrogenase is known to increase reactive oxygen species, being detrimental for cancer cells. Thiamine diphosphate (ThDP, cocarboxylase) is an essential activator of the enzyme and inhibits p53–DNA binding in cancer cells. We hypothesize that the pleiotropic regulator ThDP may be of importance for anticancer therapies. The hypothesis is tested in the present work on lung adenocarcinoma cells A549 possessing the p53–p21 pathway as fully functional or perturbed by p21 knockdown. Molecular mechanisms of ThDP action on cellular viability and their interplay with the cisplatin and p53–p21 pathways are characterized. Despite the well-known antioxidant properties of thiamine, A549 cells exhibit decreases in their reducing power and glutathione level after incubation with 5 mM ThDP, not observed in non-cancer epithelial cells Vero. Moreover, thiamine deficiency elevates glutathione in A549 cells. Viability of the thiamine deficient A549 cells is increased at a low (0.05 mM) ThDP. However, the increase is attenuated by 5 mM ThDP, p21 knockdown, specific inhibitor of the 2-oxoglutarate dehydrogenase complex (OGDHC), or cisplatin. Cellular levels of the catalytically competent ThDP·OGDHC holoenzyme are dysregulated by p21 knockdown and correlate negatively with the A549 viability. The inverse relationship between cellular glutathione and holo-OGDHC is corroborated by their comparison in the A549 and Vero cells. The similarity, non-additivity, and p21 dependence of the dual actions of ThDP and cisplatin on A549 cells manifest a common OGDHC-mediated mechanism of the viability decrease. High ThDP saturation of OGDHC compromises the redox state of A549 cells under the control of p53–p21 axes.

Sign in / Sign up

Export Citation Format

Share Document