scholarly journals Staurosporine Induces the Generation of Polyploid Giant Cancer Cells in Non-Small-Cell Lung Carcinoma A549 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Alexander Glassmann ◽  
Carmen Carrillo Garcia ◽  
Viktor Janzen ◽  
Dominik Kraus ◽  
Nadine Veit ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Inhibition Of Proliferation ◽  
Polyploid Giant Cancer Cells

Cultivation of A549 non-small-cell lung carcinoma (NSCLC) cells in the presence of staurosporine (SSP) leads to a reduction or a lack of proliferation in a concentration-dependent manner. This inhibition of proliferation is accompanied by the generation of polyploid giant cancer cells (PGCCs) that are characterized by cell flattening, increased cell size, polyploidy, and polynucleation as determined by crystal violet staining, BrdU and DiI labelling, and flow cytometry as well as video time-lapse analysis. Continuous SSP treatment of A549 cells can preserve PGCCs for at least two months in a resting state. Upon removal of SSP, A549 PGCCs restart to divide and exhibit a proliferation pattern and cellular morphology indistinguishable from cells where PGCCs originally derived from. Thus, SSP-treated A549 cells represent a simple and reliable experimental model for the reversible generation of PGCCs and their subsequent experimental analysis.

Trilinolein Inhibits Proliferation of Human Non-Small Cell Lung Carcinoma A549 Through the Modulation of PI3K/Akt Pathway

2011 ◽  
Vol 39 (04) ◽  
pp. 803-815 ◽  
Author(s):  
Pei-Yu Chou ◽  
Guan-Jhong Huang ◽  
Chun-Hsu Pan ◽  
Yi-Chung Chien ◽  
Ying-Yi Chen ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Panax Notoginseng ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Proteolytic Activation ◽  
Induced Apoptosis

Trilinolein has been identified as one of the active constituents isolated from Panax notoginseng used widely in traditional Chinese medicine. Protective actions of Panax notoginseng against cerebral ischemia, beneficial effects on the cardiovascular system, and hemostatic, antioxidant, hypolipidemic, hepatoprotective, renoprotective and estrogen-like activities have been illustrated. In the present study, the effects of trilinolein on the growth of non-small cell lung carcinoma A549 were investigated. It was found that the exposure of A549 cells to trilinolein resulted in the growth inhibition and the induction of apoptosis in a dose- and time- dependent manner. Trilinolein treatment induced the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 expression, which was associated with the proteolytic activation of caspases and the concomitant degradation of poly(ADP-ribose) polymerase (PARP) protein. Intracellular reactive oxygen species seem to play a role in the trilinolein-induced apoptosis, since ROS were produced early in the trilinolein treatment. Moreover, the activity of PI3K/Akt was downregulated in trilinolein-treated cells. Our results demonstrated that the most important regulators of trilinolein-induced apoptosis are Bcl-2 family and caspase-3, which are associated with cytochrome c release and dephosphorylation on the Akt signaling pathway.

scholarly journals Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 572 ◽  
Author(s):  
Shi-qi Lin ◽  
Fu-juan Jia ◽  
Cai-yun Zhang ◽  
Fang-yuan Liu ◽  
Jia-hui Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cycle Arrest ◽  
M Phase

Actinomycin V, extracted and separated from marine-derived actinomycete Streptomyces sp., as the superior potential replacement of actinomycin D (which showed defect for its hepatotoxicity) has revealed an ideal effect in the suppression of migration and invasion in human breast cancer cells as referred to in our previous study. In this study, the involvement of p53 in the cell cycle arrest and pro-apoptotic action of actinomycin V was investigated in human non-small-cell lung carcinoma A549 cells. Results from the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay showed that cytotoxic activity of actinomycin V on A549 cells (with wild-type p53) was stronger than the NCI-H1299 cells (p53-deficient). Actinomycin V upregulated both of the protein and mRNA expression levels of p53, p21Waf1/Cip1 and Bax in A549 cells. For this situation, actinomycin V decreased the M-phase related proteins (Cdc2, Cdc25A and Cyclin B1) expression, arrested cells in G2/M phase and subsequently triggered apoptosis by mediating the Bcl-2 family proteins’ expression (Bax and Bcl-2). Furthermore, the effects of cell cycle arrest and apoptosis in A549 cells which were induced by actinomycin V could be reversed by the pifithrin-α, a specific inhibitor of p53 transcriptional activity. Collectively, our results suggest that actinomycin V causes up-regulation of p53 by which the growth of A549 cells is suppressed for cell cycle arrest and apoptosis.

scholarly journals ADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non-small cell lung carcinoma

2020 ◽  
Vol 69 (11) ◽  
pp. 2345-2355
Author(s):  
Meng Zheng ◽  
Zhiling Zhou ◽  
Xiangting Tian ◽  
Dingzhang Xiao ◽  
Xinghua Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Poor Prognostic Factor

Abstract The cross-talk between cancer cells and monocyte-derived alveolar macrophages (Mo-AMs) promotes non-small cell lung carcinoma (NSCLC) progression. In this study, we report that both cancer cells and Mo-AMs robustly express beta 3-adrenergic receptor (ADRB3) in NSCLC. ADRB3 supports lung cancer cells proliferation and promotes chronic inflammation. Genetic and pharmacologic inhibition of ADRB3 reverses tumor growth and inflammation in mouse. Furthermore, we demonstrate that M5D1, a novel anti-ADRB3 monoclonal antibody, inhibits human lung cancer cells proliferation and inflammation via affecting the intracellular mTOR pathway and activating p53. In NSCLC patients, we confirmed that upregulation of ADRB3 expression correlates with tumor progression and poor prognosis. Altogether, these results shed light on the role of ADRB3 in NSCLC and suggest that M5D1 could become powerful antitumor weapons.

scholarly journals Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769432 ◽  
Author(s):  
Natália Jaeger ◽  
Rafael Sanguinetti Czepielewski ◽  
Maira Bagatini ◽  
Bárbara N Porto ◽  
Cristina Bonorino
Keyword(s):  
Reactive Oxygen Species ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Small Cell ◽  
Oxygen Species ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide

Nerve fibers and neurotransmitters have increasingly been shown to have a role in tumor progression. Gastrin-releasing peptide is a neuropeptide linked to tumor aggressiveness, acting as an autocrine tumor growth factor by binding to its receptor, gastrin-releasing peptide receptor, expressed by many tumors. Although neuropeptides have been previously linked to tumor cell proliferation, more recent studies have uncovered roles for neuropeptides in chemotaxis and metastasis. Understanding the precise roles of such peptides in cancer is crucial to optimizing targeted therapy design. We have previously described that gastrin-releasing peptide acts directly as a chemotactic factor for neutrophils, dependent on PI3K, ERK, and p38. In this study, we investigated roles for gastrin-releasing peptide in lung adenocarcinoma. We asked if gastrin-releasing peptide would act as a proliferative and/or chemotactic stimulus for gastrin-releasing peptide receptor–expressing tumor cells. In A549 cells, a non-small cell lung carcinoma line, the treatment with gastrin-releasing peptide leads to activation of AKT and ERK1/2, and production of reactive oxygen species. Gastrin-releasing peptide induced migration of A549 cells, dependent on gastrin-releasing peptide receptor and PI3K, but not ERK. However, no proliferation was observed in these cells in response to gastrin-releasing peptide, and gastrin-releasing peptide did not promote resistance to treatment with a chemotherapy drug. Our results suggest that, similar to what happens in neutrophils, gastrin-releasing peptide is a migratory, rather than a proliferative, stimulus, for non–small cell lung carcinoma cells, indicating a putative role for gastrin-releasing peptide and gastrin-releasing peptide receptor in metastasis.

scholarly journals Transcriptional activation of cyclin D1 via HER2/HER3 contributes to cell survival and EGFR tyrosine kinase inhibitor resistance in non-small cell lung carcinoma

2019 ◽  
Author(s):  
Bin Liu ◽  
Deng Chen ◽  
Shipeng Chen ◽  
Ali Saber ◽  
Hidde Haisma
Keyword(s):  
Lung Cancer ◽  
Cell Survival ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

AbstractSeveral different mechanisms are implicated in the resistance of lung cancer cells to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and only few have been functionally investigated. Here, using genetically knocked out EGFR and TKI-resistant lung cancer cells, we show that loss of wild-type EGFR attenuates cell proliferation, migration and 3D-spherid formation, whereas loss of mutant EGFR or resistance to TKIs reinforces those processes. Consistently, disruption of wild-type EGFR leads to suppression of HER2/HER3, while mutant EGFR ablation or resistance to TKIs increases HER2/HER3 expression, compensating for EGFR loss. Furthermore, HER2/HER3 nuclear translocation mediates overexpression of cyclin D1, leading to tumor cell survival and drug resistance. Cyclin D1/CDK4/6 inhibition resensitizes erlotinib-resistant (ER) cells to erlotinib. Analysis of cyclin D1 expression in patients with non-small cell lung carcinoma (NSCLC) showed that its expression is negatively associated with overall survival and disease-free survival. Our results provide biological and mechanistic insights into targeting EGFR and TKI resistance.

Targeting apoptosis by 1,2-diazole through regulation of EGFR, Bcl-2 and CDK-2 mediated signaling pathway in human non-small cell lung carcinoma A549 cells

Gene ◽  
2018 ◽  
Vol 679 ◽  
pp. 352-359 ◽  
Author(s):  
Venugopal Vinod Prabhu ◽  
Perumal Elangovan ◽  
Sivasithambaram Niranjali Devaraj ◽  
Kunnathur Murugesan Sakthivel
Keyword(s):  
Signaling Pathway ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma
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