scholarly journals Nutlin-3-Induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis Through Repression of Akt1/Wnt Signaling

2019 ◽  
Vol 27 (9) ◽  
pp. 987-995
Author(s):  
Meng Wang ◽  
Xin Wang ◽  
Yuan Li ◽  
Qiang Xiao ◽  
Xiao-Hai Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cell Division ◽  
Small Cell Lung Cancer ◽  
Wnt Signaling ◽  
Small Cell ◽  
Small Cell Lung ◽  
P53 Expression ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

The aim of this study was to investigate the potential biological activities of nutlin-3 in the regulation of growth and proliferation of non-small cell lung cancer (NSCLC) stem cells (CSCs), which may help in sensitizing to axitinib-induced apoptosis. Nutlin-3 induction of p53 expression was used to test its role in controlling the cell division pattern and apoptosis of NSCLC cells. A549 cells and H460 cells were pretreated with nutlin-3 and then treated with either an Akt1 activator or shRNA-GSK3β, to investigate the potential role of p53 sensitization in the biological effects of axitinib. We also determined the expression levels of GSK3β and p-Akt1 in patients with NSCLC and determined their potential association with survival data using Kaplan‐Meier plots and CBIOTAL. Increased p53 expression stimulated the induction of apoptosis by axitinib and promoted asymmetric cell division (ACD) of NSCLC CSCs. The repression of Akt phosphorylation induced by nutlin-3 promoted the ACD of lung CSCs, decreasing the proportion of the stem cell population. In addition to the induction of apoptosis by axitinib through inhibition of Wnt signaling, nutlin-3 treatment further enhanced axitinib-induced apoptosis by inhibiting Akt1/GSK3β/Wnt signaling. The low expression of GSK3β and increased expression of p-Akt in patients with NSCLC were closely associated with the development of NSCLC. TP53 stimulates the induction of apoptosis in NSCLC by axitinib and the ACD of lung CSCs through its regulatory effects on the p53/Akt/GSK3β pathways.

scholarly journals Structural characterization of Momordica charantia L. (Cucurbitaceae) oligopeptides and the detection of their capability in non-small cell lung cancer A549 cells: induction of apoptosis

RSC Advances ◽  
2019 ◽  
Vol 9 (15) ◽  
pp. 8300-8309
Author(s):  
Jiao Dong ◽  
Xianxin Zhang ◽  
Chunxiao Qu ◽  
Xuedong Rong ◽  
Jie Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Structural Characterization ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

MCLO-12 induced apoptosis by up-regulating the ROS, activating the caspases expressions, suppressing the Trx system and subsequently activating a number of Trx-dependent pathways.

Wnt Signaling in Stem Cells and Non–Small-Cell Lung Cancer

2005 ◽  
Vol 7 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Biao He ◽  
Richard N. Barg ◽  
Liang You ◽  
Zhidong Xu ◽  
Noemi Reguart ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Small Cell Lung Cancer ◽  
Wnt Signaling ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

LIFE SPAN PREDICTION AT METASTATIC NON-SMALL CELL LUNG CANCER

2018 ◽  
Vol 64 (4) ◽  
pp. 522-527
Author(s):  
Aleksey Shutko ◽  
Viktor Mus
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Small Cell Lung Cancer ◽  
Life Span ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Small Cell ◽  
Hemopoietic Stem Cells ◽  
Small Cell Lung ◽  
Individual Life

Individual parameters of circulating hemopoietic stem cells (HSC) lymphoid origin were measured by cytofluorometry before treatment of patients with metastatic non-small cell lung cancer and were retrospectively compared with individual life span's (LS). The possibility of poor prognosis of treatment's results (LS

scholarly journals N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5

2018 ◽  
Vol 45 (5) ◽  
pp. 2054-2070 ◽  
Author(s):  
Ye Liang ◽  
Wenhua Xu ◽  
Shihai Liu ◽  
Jingwei Chi ◽  
Jisheng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Sodium Dodecyl ◽  
Death Receptor ◽  
Small Cell ◽  
Clinical Samples ◽  
Small Cell Lung ◽  
Induced Apoptosis

Background/Aims: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL. Methods: In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo. Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5. After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting. Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope. Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC). O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown. Results: We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis. Furthermore, GlcNAc promoted DR5 clustering by improving its O-glycosylation. Conclusion: These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.

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