scholarly journals Nurr1 promotes lung cancer apoptosis via enhancing mitochondrial stress and p53-Drp1 pathway

2019 ◽  
Vol 14 (1) ◽  
pp. 262-274
Author(s):  
Shu Zhao ◽  
Peng Li ◽  
Peng Wang ◽  
Jing Yang ◽  
Peng Song ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Lung Cancer Death ◽  
Mitochondrial Stress ◽  
Mitochondrial Homeostasis ◽  
A549 Lung

AbstractObjectiveMitochondrial homeostasis is vital for the progression of lung cancer. Nurr1 has been identified as a novel mediator of mitochondrial homeostasis in several types of cancers. The aim of our study was to investigate whether Nurr1 modulates the viability of A549 lung cancer cells by inducing mitochondrial dysfunction, with a focus on the p53-Drp1 signaling pathway.Methodswestern blotting, ELISA and immunofluorescence assay was used to verify the alterations of cell death. siRNA was used to determine the role of p53-Drp1 pathway in lung cancer death.ResultsNurr1 was downregulated in A549 lung cancer cells compared to normal pulmonary epithelial cells. Interestingly, overexpression of Nurr1 reduced the viability of A549 lung cancer cells by activating apoptosis and mitochondrial stress. At the molecular level, we provide data to support the regulatory effects of Nurr1 on the p53-Drp1 signaling pathway. Blockade of the p53-Drp1 signaling pathway abolished the proapoptotic action of Nurr1 on A549 cells and sustained mitochondrial homeostasis.ConclusionTaken together, our results depict the tumor-suppressive role played by Nurr1 in A549 lung cancer in vitro and show that the anticancer effects of Nurr1 are executed via triggering of mitochondrial dysfunction and activation of the p53-Drp1 signaling pathway.

Diallyl disulphide suppresses the cannonical Wnt signaling pathway and reverses the fibronectin-induced epithelial mesenchymal transition of A549 lung cancer cells

2019 ◽  
Vol 10 (1) ◽  
pp. 191-202 ◽  
Author(s):  
Bornita Das ◽  
Dona Sinha
Keyword(s):  
Lung Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
A549 Lung

DADS reflected the potential of reversal of FN-induced EMT by inhibition of Wnt signaling in A549 lung cancer cells.

MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in A549 lung cancer cells via influencing reactive oxygen species and GSH level

2010 ◽  
Vol 29 (7) ◽  
pp. 607-614 ◽  
Author(s):  
Yong Hwan Han ◽  
Woo Hyun Park
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Proteasome Inhibitor ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Oxygen Species ◽  
A549 Lung

Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). In the present study, we evaluated the effects of MG132 on the growth of A549 lung cancer cells in relation to cell growth, ROS and glutathione (GSH) levels. Treatment with MG132 inhibited the growth of A549 cells with an IC50 of approximately 20 μM at 24 hours. DNA flow cytometric analysis indicated that 0.5 ∼ 30 μM MG132 induced a G1 phase arrest of the cell cycle in A549 cells. Treatment with 10 or 30 μM MG132 also induced apoptosis, as evidenced by sub-G1 cells and annexin V staining cells. This was accompanied by the loss of mitochondrial membrane potential (MMP; Δψm). The intracellular ROS levels including O2•- were strongly increased in 10 or 30 μM MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 μM MG132-treated cells. Furthermore, 10 or 30 μM MG132 increased mitochondrial O2•- level but 0.1, 0.5 or 1 μM MG132 decreased that. In addition, 10 or 30 μM MG132 induced GSH depletion in A549 cells. In conclusion, MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels. Our present data provide important information on the anti-growth mechanisms of MG132 in A549 lung cancer cells in relation to ROS and GSH.

Effects of Intermittent Cisplatin Intervention on 6PGD Levels and Tumor Growth and Migration in A549 Lung Cancer Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
WU Qiang ◽  
TANG Lin-dong ◽  
WU Yan-hui ◽  
LI Qiang ◽  
YU Li
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Western Blot ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration Ability ◽  
Western Blot Method ◽  
And Migration ◽  
A549 Lung

Aim: To investigate the changes of A549 protein 6PGD expression, tumor growth and migration, NADPH and ROS levels in lung cancer cells after intermittent intervention with DDP. Methods: The sensitivity of A549 cells to DDP was detected by cck-8 method, A549 cells were treated by DDP intermitten, 6PGD protein expression was detected by Western blot method, and the ROS level of A549 cells was determined by ROS kit. NADPH levels of A549 cells were determined by NADPH kit. Result: After DDP intermittent intervention, the expression of 6PGD protein in lung cancer cells A549 was increased, the growth and migration of A549 cells were significantly inhibited, and ROS and NADPH levels were significantly increased. Conclusion: 6PGD were upregulated in after DDP intermittent intervention and affected the migration ability in lung cancer cells.

Melatonin suppresses doxorubicin-induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction

2012 ◽  
Vol 53 (4) ◽  
pp. 335-343 ◽  
Author(s):  
Naree Song ◽  
Ae Jeong Kim ◽  
Hyun-Ju Kim ◽  
Hye Jin Jee ◽  
Minjee Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Premature Senescence ◽  
A549 Lung

BMP4 signaling induces senescence and modulates the oncogenic phenotype of A549 lung adenocarcinoma cells

2004 ◽  
Vol 286 (1) ◽  
pp. L81-L86 ◽  
Author(s):  
S. Buckley ◽  
W. Shi ◽  
B. Driscoll ◽  
A. Ferrario ◽  
K. Anderson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Telomerase Activity ◽  
Lung Cancer Cells ◽  
Senescent Phenotype ◽  
A549 Lung

Lung cancer is the most common visceral malignancy in males, with rapidly increasing incidence in females, and a devastatingly poor prognosis. Transforming growth factor (TGF)-β has been shown to induce senescence in A549 lung cancer cells, and both TGF-β and bone morphogenetic protein (BMP) 2 can suppress the transformed phenotype of A549 cells in vitro. We examined the effects of BMP4, another member of the TGF-β superfamily, on specific oncogenic properties of A549 cancer cells. When A549 cancer cells were treated continuously with 100 ng/ml of BMP4, a senescent phenotype was observed after 2 wk of treatment. The BMP-treated cells appeared larger than untreated cells, grew more slowly, had more senescence-associated β-galactosidase activity, and had less telomerase activity, as measured by the telomeric repeat amplification protocol assay. Invasion through Engelbreth Holm-Swarm matrix was inhibited in the senescent cell population. Senescent BMP4-treated cells had lower ERK activation, VEGF expression, and Bcl2 expression than wild-type cells, consistent with a less proliferative, less angiogenic phenotype with increased susceptibility to death by apoptosis. BMP4 treatment also resulted in sustained elevation of Smad1. In vivo xenograft studies in the flanks of nude mice confirmed that the BMP-treated cells were significantly less tumorigenic than untreated cells. Direct overexpression of Smad1 using adenoviral constructs resulted in cell death within 5 days. These studies suggest that BMP4 pathway signaling can induce senescence and thus negatively regulate the growth of A549 lung cancer cells.

scholarly journals Anti-proliferation effect of Scutellaria barbata D. Don extract on lung cancer

2021 ◽  
Vol 18 (9) ◽  
pp. 1867-1872
Author(s):  
Zhang Hu ◽  
Duan Jing
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Blue Staining ◽  
G1 Phase ◽  
Scutellaria Barbata ◽  
A549 Lung

Purpose: To investigate the effect of Scutellaria barbata D. Don extract (SBDE) on apoptosis and proliferation in A549 human lung cancer cells. Methods: Inverted microscope was used to observe morphological changes in A549 cells after exposure to SBDE. Trypan blue staining of living cells was applied to construct cell growth curve after treatment with varying concentrations of SBDE. The influence of SBDE on cell proliferation, apoptosis and cell cycle was determined by MTT assay while protein expressions of key apoptosis-related enzymes were evaluated by immuno-cytochemical method. Results: SBDE inhibited the growth of A549 lung cancer cells at a concentration range of 20 - 160 μg/mL. Flow cytometry showed that SBDE induced apoptosis in the A549 cells. The proportion of cells in G0/G1-phase increased significantly (p < 0.01), while the proportion of cells in S-phase and G2/Mphase decreased correspondingly, indicating that the cells were in G0/G1-phase arrest. Cell cycle arrest and apoptosis-inducing effect gradually increased with increase in SBDE concentration. With increasing concentrations of SBDE, there were significant increases in the expressions of caspase-3 (p < 0.05), caspase-8 (p < 0.01) and caspase-9 (p < 0.05), and significant decreases in Ki-67 (p < 0.01) and p21 ras protein (p < 0.01). Conclusion: SBDE exerts significant inhibitory effect on the proliferation of A549 lung cancer cells, which can be developed for the treatment of lung cancer patients.

scholarly journals UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinhong Zhu ◽  
Haijiao Ao ◽  
Mingdong Liu ◽  
Kui Cao ◽  
Jianqun Ma
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Risk Score ◽  
A549 Cells ◽  
Mtor Signaling ◽  
Lung Cancer Cells ◽  
Mtor Signaling Pathway

Abstract Background Ubiquitin-conjugating enzyme E2T (UBE2T) acts as an oncogene in various types of cancer. However, the mechanisms behind its oncogenic role remain unclear in lung cancer. This study aims to explore the function and clinical relevance of UBE2T in lung cancer. Methods Lentiviral vectors were used to mediate UBE2T depletion or overexpress UBE2T in lung cancer cells. CCK8 analysis and western blotting were performed to investigate the effects of UBE2T on proliferation, autophagy, and relevant signaling pathways. To exploit the clinical significance of UBE2T, we performed immunohistochemistry staining with an anti-UBE2T antibody on 131 NSCLC samples. Moreover, we downloaded the human lung adenocarcinoma (LUAD) dataset from The Cancer Atlas Project (TCGA). Lasso Cox regression model was adopted to establish a prognostic model with UBE2T-correlated autophagy genes. Results We found that UBE2T stimulated proliferation and autophagy, and silencing this gene abolished autophagy in lung cancer cells. As suggested by Gene set enrichment analysis, we observed that UBE2T downregulated p53 levels in A549 cells and vice versa. Blockade of p53 counteracted the inhibitory effects of UBE2T depletion on autophagy. Meanwhile, the AMPK/mTOR signaling pathway was activated during UBE2T-mediated autophagy, suggesting that UBE2T promotes autophagy via the p53/AMPK/mTOR pathway. Interestingly, UBE2T overexpression increased cisplatin-trigged autophagy and led to cisplatin resistance of A549 cells, whereas inhibiting autophagy reversed drug resistance. However, no association was observed between UEB2T and overall survival in a population of 131 resectable NSCLC patients. Therefore, we developed and validated a multiple gene signature by considering UBE2T and its relevance in autophagy in lung cancer. The risk score derived from the prognostic signature significantly stratified LUAD patients into low- and high-risk groups with different overall survival. The risk score might independently predict prognosis. Interestingly, nomogram and decision curve analysis demonstrated that the signature’s prognostic accuracy culminated while combined with clinical features. Finally, the risk score showed great potential in predicting clinical chemosensitivity. Conclusions We found that UBE2T upregulates autophagy in NSCLC cells by activating the p53/AMPK/mTOR signaling pathway. The clinical predicting ability of UBE2T in LUAD can be improved by considering the autophagy-regulatory role of UBE2T.

scholarly journals Induction of Cell Death in Human A549 Cells Using 3-(Quinoxaline-3-yl) Prop-2-ynyl Methanosulphonate and 3-(Quinoxaline-3-yl) Prop-2-yn-1-ol

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 407 ◽  
Author(s):  
Mixo Sibiya ◽  
Lerato Raphoko ◽  
Dikgale Mangokoana ◽  
Raymond Makola ◽  
Winston Nxumalo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Radical Scavenging ◽  
A549 Cells ◽  
Reducing Power ◽  
Lung Cancer Cells ◽  
Ros Production ◽  
Quinoxaline Derivatives ◽  
A549 Lung

Despite major advancements in the development of various chemotherapeutic agents, treatment for lung cancer remains costly, ineffective, toxic to normal non-cancerous cells, and still hampered by a high level of remissions. A novel cohort of quinoxaline derivatives designed to possess a wide spectrum of biological activities was synthesized with promising targeted and selective anticancer drug activity. Hence, this study was aimed at determining in vitro anticancer activity effects of a newly synthesized class of 3-(quinoxaline-3-yl) prop-2-ynyl quinoxaline derivatives on A549 lung cancer cells. An assessment of the quinoxaline derivatives ferric reducing power, free radical scavenging activity, cytotoxic activity, and ability to induce reactive oxygen species (ROS) production was performed using the Ferric Reducing Antioxidant Power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) assays, respectively. The ability of the quinoxaline derivatives to induce apoptosis in A549 cells was assessed using the Acridine Orange/Ethidium Bromide (AO/EB) and Annexin V-FITC/Dead Cell Assay. Of the four quinoxaline derivatives tested, 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate (LA-39B) and 3-(quinoxaline-3-yl) prop-2-yn-1-ol (LA-55) displayed a dose-dependent reducing power, free-radical scavenging activity, inhibition of cell viability, and stimulation of ROS production which was accompanied by induction of apoptosis in A549 lung cancer cells. None of the quinoxaline derivatives induced cell death or ROS production in non-cancerous Raw 267.4 macrophage cells. Cytotoxicity was observed in A549 lung cancer, HeLa cervical cancer, and MCF-7 breast cancer cells albeit inhibition was more pronounced in A549 cells. The results of the study suggest that 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate and 3-(quinoxaline-3-yl) prop-2-yn-1-ol induce apoptotic cell death in A549 lung cancer cells.

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