Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

2020 ◽  
Vol 20 (8) ◽  
pp. 982-988 ◽  
Author(s):  
Le-Le Zhang ◽  
Han Bao ◽  
Yu-Lian Xu ◽  
Xiao-Ming Jiang ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Biological Activities ◽  
A549 Cells ◽  
Immunofluorescence Assay ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

scholarly journals The Potential Role of Cathepsin K in Non-Small Cell Lung Cancer

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4136
Author(s):  
Hui Yang ◽  
Jasmine Heyer ◽  
Hui Zhao ◽  
Shengxian Liang ◽  
Rui Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Cathepsin K ◽  
Small Cell ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Small Cell Lung

(1) Background: Cathepsin K has been found overexpressed in several malignant tumors. However, there is little information regarding the involvement of Cathepsin K in non-small cell lung cancer (NSCLC). (2) Methods: Cathepsin K expression was tested in human NSCLC cell lines A549 and human embryo lung fibroblast MRC-5 cells using Western blot and immunofluorescence assay. Cathepsin K was transiently overexpressed or knocked down using transfection with a recombinant plasmid and siRNA, respectively, to test the effects on cell proliferation, migration, invasion, and on the mammalian target of rapamycin (mTOR) signaling pathway. (3) Results: Expression of Cathepsin K was increased significantly in A549 cells and diffused within the cytoplasm compared to the MRC-5 cells used as control. Cathepsin K overexpression promoted the proliferation, migration, and invasion of A549 cells, accompanied by mTOR activation. Cathepsin K knockdown reversed the above malignant behavior and inhibited the mTOR signaling activation, suggesting that Cathepsin K may promote the progression of NSCLC by activating the mTOR signaling pathway. (4) Conclusion: Cathepsin K may potentially represent a viable drug target for NSCLC treatment.

scholarly journals Aloperine inhibits the progression of non-small-cell lung cancer through the PI3K/Akt signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fujuan Liu ◽  
Tao Liu ◽  
Haiying Li
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Akt Signaling ◽  
Small Cell ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Small Cell Lung

Abstract Background Lung cancer has become the leading cause of cancer-related death worldwide and non‐small‐cell lung cancer (NSCLC) accounts for approximately 85% of cases. Aloperine (ALO), an alkaloid active natural component from S. alopecuroide, has been found to exhibit anti-inflammatory, anti-tumor and anti-viral activity. However, Whether ALO exerts anti-tumor function on NSCLC remains poorly understood, and the underlying mechanisms remain unknown. Methods The CCK-8, colony formation, cell apoptosis with flow cytometry, wound healing and transwell cell invasion assays, were used to analyze the tumor progression of H1299 and A549 cells treated with ALO in vitro, and the xenograft model was constructed to assess the effect of ALO in vivo. The expression of protein was detected by Western blotting. Results ALO suppressed the cell proliferation, self-renewal, migration and invasion, induced apoptosis in A549 and H1299 cell. Furthermore, ALO significantly enhanced the level of cytochrome c in cytosol, and resulted in the dramatical increased levels of the cleaved caspase-3, caspased-9 and PARP. ALO also inhibited the expression of MMP-2 and MMP-9. Additionally, ALO also reduced p-AKT and p-mTOR to attenuate the PI3K/AKT signaling pathway. Conclusion This study unveils a rationale for ALO through PI3K/Akt signaling pathway affecting the cell progression such as cell growth, apoptosis and invasion, and ALO acts as a potential chemotherapeutic agent for NSCLC.

scholarly journals 125I Seed Promotes Apoptosis in Non-small Lung Cancer Cells via the p38 MAPK-MDM2-p53 Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Zhang ◽  
ZhiQiang Mo ◽  
Guangfeng Duan ◽  
Rijie Tang ◽  
Fujun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Purpose:125I seeds were effective in the treatment of non-small cell lung cancer in previous research. However, the exact signaling pathway-mediated apoptosis mechanism is still unclear. The present study analyzed the effects and potential mechanisms of 125I seed on the growth and migration of A549 cells.Methods: Lung cancer A549 cells were irradiated with 125I seed for various times. MTT, invasion assay, and flow cytometry were used to detect the proliferation, invasion, and apoptosis of treated cells, respectively. A Nimblegen genome-wide expression profile chip was used to evaluate gene expression changes in 125I seed-treated A549 cells. Validation studies were performed using phosphorylated protein chip technology, Western blot, nude mouse tumor xenograft assay, and immunohistochemical experiments. All statistical analyses were performed using unpaired Student's t tests and Kruskal-Wallis test.Results: Irradiation with 125I seed inhibited A549 cell proliferation and invasion and induced apoptosis (primarily early apoptosis). Irradiation with 125I seed also caused the downregulation of p38MAPK, degradation of mouse double-minute 2 homolog (MDM2), and higher expression of p53, which eventually resulted in non-small cell lung cancer cell apoptosis.Conclusion:125I seed irradiation activated the p38MAPK/MDM2/p53 signaling pathway and promoted non-small cell lung cancer cell apoptosis. Future clinical studies targeting this signal may provide a new potential therapeutic approach for non-small cell lung cancer.

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