scholarly journals Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

2012 ◽  
Vol 50 (1) ◽  
pp. 58-67 ◽  
Author(s):  
Agnieszka Żuryń ◽  
Maciej Gagat ◽  
Aleksandra Antonina Grzanka ◽  
Lidia Gackowska ◽  
Alina Grzanka
Keyword(s):  
Cell Death ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Cyclin B1 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

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 Toxoplasma GRA16 Inhibits NF-κB Activation through PP2A-B55 Upregulation in Non-Small-Cell Lung Carcinoma Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6642
Author(s):  
Seung-Hwan Seo ◽  
Sang-Gyun Kim ◽  
Ji-Hun Shin ◽  
Do-Won Ham ◽  
Eun-Hee Shin
Keyword(s):  
Cell Cycle ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Xenograft Model ◽  
Cyclin B1 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Anticancer Effects ◽  
Mouse Xenograft Model

Nuclear factor kappa B (NF-κB) activation is a well-known mechanism by which chemoresistance to anticancer agents is reported. It is well-known that irinotecan as a chemotherapeutic drug against non-small-cell lung carcinoma (NSCLC) has limited anticancer effect due to NF-κB activation. In this study, we propose the novel role of GRA16, a dense granule protein of Toxoplasma gondii, as an anticancer agent to increase the effectiveness of chemotherapy via the inhibition of NF-κB activation. To demonstrate this, H1299 cells were stably transfected with GRA16. The anticancer effects of GRA16 were demonstrated as a reduction in tumor size in a mouse xenograft model. GRA16 directly elevated B55 regulatory subunit of protein phosphatase 2A (PP2A-B55) expression in tumor cells, thereby decreasing GWL protein levels and ENSA phosphorylation. This cascade, in turn, induced PP2A-B55 activation and suppressed AKT/ERK phosphorylation and cyclin B1 levels, suggesting reduced cell survival and arrested cell cycle. Moreover, PP2A-B55 activation and AKT phosphorylation inhibition led to NF-κB inactivation via the reduction in inhibitory kappa B kinase beta (IKKβ) levels, de-phosphorylation of inhibitor of kappa B alpha (IκBα), and reduction in the nuclear transit of NF-κB p65. Furthermore, this molecular mechanism was examined under irinotecan treatment. The PP2A-B55/AKT/NF-κB p65 pathway-mediated anticancer effects were only induced in the presence of GRA16, but not in the presence of irinotecan. Moreover, GRA16 synergistically promoted the anticancer effects of irinotecan via the induction of the sub-G1 phase and reduction of cell proliferation. Collectively, irinotecan and GRA16 co-treatment promotes the anticancer effects of irinotecan via NF-κB inhibition and cell cycle arrest induced by GRA16, subsequently increasing the chemotherapeutic effect of irinotecan to NSCLC cells via NF-κB inhibition.

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.

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