scholarly journals Effects of water-soluble components of atmospheric particulates from rare earth mining areas in China on lung cancer cell cycle

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuan Xia ◽  
Xulong Zhang ◽  
Dejun Sun ◽  
Yumin Gao ◽  
Xiaoe Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Rare Earth ◽  
A549 Cell ◽  
A549 Cells ◽  
Cyclin B1 ◽  
Water Soluble ◽  
Differentially Expressed ◽  
M Phase ◽  
Cell Arrest

Abstract Background This study aims to investigate the effects of water soluble particulate matter (WSPM) on the viability and protein expression profile of human lung adenocarcinoma cell A549 in the Bayou Obo rare earth mining area, and explore the influence of WSPM on the A549 cell cycle. Results It was found that WSPM can inhibit the viability of A549 cells and induce cell arrest in the G2/M phase. Compared with controls, exposure to WSPM10 and WSPM2.5 induced 134 and 116 proteins to be differentially expressed in A549 cells, respectively. In addition, 33 and 31 differentially expressed proteins were further confirmed, and was consistent with the proteomic analysis. The most prominent enrichment in ribosome-associated proteins were presented. When RPL6, RPL13, or RPL18A gene expression was inhibited, A549 cells were arrested in the G1 phase, affecting the expression of Cyclin D1, p21, RB1, Cyclin A2, Cyclin B1, CDC25A, CDK2, CHEK2 and E2F1. Furthermore, the La3+, Ce3+, Nd3+ and F- in WSPM also inhibited the viability of A549 cells. After 24 h of exposure to 2 mM of NaF, A549 cells were also arrested in the G2/M phase, while the other three compounds did not have this effect. These four compounds affected the cell cycle regulatory factors in A549 cells, mainly focusing on effecting the expression of CDK2, CDK4, RB1, ATM, TP53 and MDM2 genes. These results are consistent with the those from WSPM exposure. Conclusions These results revealed that WSPM from rare earth mines decreased the viability of A549 cells, and induced cell cycle G2/M phase arrest, and even apoptosis, which may be independent of the NF-κB/MYD88 pathway, and be perceived by the TLR4 receptor. The dysfunction of the cell cycle is correlated to the down-expression of ribosomal proteins (RPs). However, it is not the direct reason for the A549 cell arrest in the G2/M phase. La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. These results indicate the importance for further research into the relationship between APM and lung cancer.

scholarly journals TLC388 Induces DNA Damage and G2 Phase Cell Cycle Arrest in Human Non-Small Cell Lung Cancer Cells

2020 ◽  
Vol 27 (1) ◽  
pp. 107327481989797
Author(s):  
Kun-Ming Wu ◽  
Chih-Wen Chi ◽  
Jerry Cheng-Yen Lai ◽  
Yu-Jen Chen ◽  
Yu Ru Kou
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cyclin B1 ◽  
Small Cell ◽  
Phase Cell ◽  
Small Cell Lung ◽  
Cycle Arrest ◽  
M Phase ◽  
G2 Phase ◽  
Induced Apoptosis

TLC388, a camptothecin-derivative targeting topoisomerase I, is a potential anticancer drug. In this study, its effect on A549 and H838 human non-small cell lung cancer (NSCLC) cells was investigated. Cell viability and proliferation were determined by thiazolyl blue tetrazolium bromide and clonogenic assays, respectively, and cell cycle analysis and detection of phosphorylated histone H3 (Ser10) were performed by flow cytometry. γ-H2AX protein; G2/M phase-associated molecules ataxia-telangiectasia mutated (ATM), CHK1, CHK2, CDC25C, CDC2, and cyclin B1; and apoptosis were assessed with immunofluorescence staining, immunoblotting, and an annexin V assay, respectively. The effect of co-treatment with CHIR124 (a checkpoint kinase 1 [CHK1] inhibitor) was also studied. TLC388 decreased the viability and proliferation of cells of both NSCLC lines in a dose-dependent manner. TLC388 inhibited the viability of NSCLC cell lines with an estimated concentration of 50% inhibition (IC50), which was 4.4 and 4.1 μM for A549 and H838 cells, respectively, after 24 hours. Moreover, it resulted in the accumulation of cells at the G2/M phase and increased γ-H2AX levels in A549 cells. Levels of the G2 phase–related molecules phosphorylated ATM, CHK1, CHK2, CDC25C, and cyclin B1 were increased in TLC388-treated cells. CHIR124 enhanced the cytotoxicity of TLC388 toward A549 and H838 cells and induced apoptosis of the former. TLC388 inhibits NSCLC cell growth by inflicting DNA damage and activating G2/M checkpoint proteins that trigger G2 phase cell cycle arrest to enable DNA repair. CHIR124 enhanced the cytotoxic effect of TLC388 and induced apoptosis.

3,3′,5,5′-tetramethoxybiphenyl-4,4′diol induces cell cycle arrest in G2/M phase and apoptosis in human non-small cell lung cancer A549 cells

2020 ◽  
Vol 326 ◽  
pp. 109133 ◽  
Author(s):  
Virginia Marcia Concato ◽  
Fernanda Tomiotto-Pellissier ◽  
Taylon Felipe Silva ◽  
Manoela Daiele Gonçalves ◽  
Bruna Taciane da Silva Bortoleti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Cycle Arrest ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cycle Arrest ◽  
M Phase

Cytotoxicity of withasteroids: withametelin induces cell cycle arrest at G2/M phase and mitochondria-mediated apoptosis in non-small cell lung cancer A549 cells

Tumor Biology ◽  
2016 ◽  
Vol 37 (9) ◽  
pp. 12579-12587 ◽  
Author(s):  
Poorna Chandra Rao ◽  
Sajeli Begum ◽  
Mohammad Ali Farboodniay Jahromi ◽  
Zahra Hosseini Jahromi ◽  
Saketh Sriram ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Cycle Arrest ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cycle Arrest ◽  
M Phase

scholarly journals 2-(6-Hydroxyhexylthio)-5,8-dimethoxy-1,4-naphthoquinone Induces Apoptosis through ROS-Mediated MAPK, STAT3, and NF-κB Signalling Pathways in Lung Cancer A549 Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Gui-Nan Shen ◽  
Cheng Wang ◽  
Ying-Hua Luo ◽  
Jia-Ru Wang ◽  
Rui Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
Western Blot ◽  
Cancer Cells ◽  
A549 Cell ◽  
A549 Cells ◽  
Cyclin B1 ◽  
Lung Cancer Cells ◽  
Signalling Pathways ◽  
Intrinsic Pathway

Two novel compounds, 2-(2-hydroxyethylthio)-5,8-dimethoxy-1,4-naphthoquinone (HEDMNQ) and 2-(6-hydroxyhexylthio)-5,8-dimethoxy-1,4-naphthoquinone (HHDMNQ), were synthesized to investigate the kill effects and mechanism of 1,4-naphthoquinone derivatives in lung cancer cells. The results of the CCK-8 assay showed that HEDMNQ and HHDMNQ had significant cytotoxic effects on A549, NCI-H23, and NCI-H460 NSCLC cells. Flow cytometry and western blot results indicated that HHDMNQ induced A549 cell cycle arrest at the G2/M phase by decreasing the expression levels of cyclin-dependent kinase 1/2 and cyclin B1. Fluorescence microscopy and flow cytometry results indicated that HHDMNQ could induce A549 cell apoptosis, and western blot analysis showed that HHDMNQ induced apoptosis through regulating the mitochondria pathway, as well as the MAPK, STAT3, and NF-κB signalling pathways. Flow cytometry results showed that intracellular reactive oxygen species (ROS) levels were increased after HHDMNQ treatment, and western blot showed that ROS could modulate the intrinsic pathway and MAPK, STAT3, and NF-κB signalling pathways. These effects were blocked by the ROS inhibitor N-acetyl-L-cysteine in A549 cells. Our findings suggest that compared with HEDMNQ, HHDMNQ had the stronger ability to inhibit the cell viability of lung cancer cells and induce apoptosis by regulating the ROS-mediated intrinsic pathway and MAPK/STAT3/NF-κB signalling pathways. Thus, HHDMNQ might be a potential antitumour compound for treating lung cancer.

scholarly journals Digoxin enhances radiation response in radioresistant A549 cells by reducing protein phosphatase 2A

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Ji Young Lee ◽  
Mi-Sook Kim ◽  
Mi So Lee ◽  
Jae Eun Ju ◽  
Namhyun Chung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
A549 Cells ◽  
Cyclin B1 ◽  
Differential Sensitivity ◽  
Promising Therapeutic Approach ◽  
Phosphatase 2A ◽  
Pp2a Inhibitor

Protein phosphatase 2A (PP2A) is a ubiquitous multifunctional enzyme usually known as a tumor suppressor. Recent studies have reported that although inhibition of PP2A leads to acceleration of cell growth, it also induces damaged cells to pass through the cell cycle and renders them sensitive to radiotherapy. Here, we investigated the radiosensitizing effects of digoxin as a PP2A inhibitor in two non-small-cell lung cancer (NSCLC) cell types (H460 and A549) with differential sensitivity to radiation. Digoxin inhibited the proliferation of H460 and A549 cells in a dose-dependent fashion and was especially effective on radioresistant A549 cells. Interestingly, the radiosensitizing effect of digoxin was only present in the radioresistant A549 cells and xenografts. The combination of digoxin and ionizing radiation (IR) significantly reduced clonogenic survival and xenograft tumor growth (P<0.001), compared with IR alone. Digoxin suppressed PP2A protein expression and prevented IR-induced PP2A expression in A549 cells. Digoxin treatment combined with IR allowed the damaged cell to progress through the cell cycle via suppression of cell cycle-related proteins (p53, cyclin D1, cyclin B1, CDK4, and p-cdc2). Moreover, digoxin enhanced IR-induced DNA damage through reduction in levels of repair proteins and elevation of p-ATM foci formation up to 24 h (P<0.001). In conclusion, digoxin has a novel function as a PP2A inhibitor, and combined with IR produces a synergistic effect on radiosensitizing cells, thereby indicating a potentially promising therapeutic approach to radioresistant lung cancer treatment.

scholarly journals The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Hosami ◽  
Azadeh Manayi ◽  
Vahid Salimi ◽  
Farshad Khodakhah ◽  
Mitra Nourbakhsh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Caspase 3 ◽  
Cannabis Sativa ◽  
A549 Cells ◽  
Echinacea Purpurea ◽  
G1 Phase ◽  
Cell Cycle Distribution ◽  
Cb2 Receptor ◽  
Anti Cancer

Abstract Background Considering the advantages of using medicinal herbs as supplementary treatments to sensitize conventional anti-cancer drugs, studying functional mechanisms and regulatory effects of Echinacea purpurea (as a non-cannabinoid plant) and Cannabis sativa (as a cannabinoid plant) are timely and required. The potential effects of such herbs on lung cancer cell growth, apoptosis, cell cycle distribution, cellular reactive oxygen species (ROS) level, caspase activity and their cannabinomimetic properties on the CB2 receptor are addressed in the current study. Methods The cytotoxic effect of both herb extracts on the growth of lung cancer cells (A549) was assessed using the MTT assay. The annexin-V-FITC staining and propidium iodide (PI) staining methods were applied for the detection of apoptosis and cell cycle distribution using flow cytometry. The cellular level of ROS was measured using 7′-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe in flow cytometry. The caspase 3 activity was assessed using a colorimetric assay Kit. Results Echinacea purpurea (EP) root extract induced a considerable decrease in A549 viable cells, showing a time and dose-dependent response. The cell toxicity of EP was accompanied by induction of early apoptosis and cell accumulation at the sub G1 phase of the cell cycle. The elevation of cellular ROS level and caspase 3 activity indicate ROS-induced caspase-dependent apoptosis following the treatment of A549 cells by EP extract. The observed effects of EP extract on A549 growth and death were abrogated following blockage of CB2 using AM630, a specific antagonist of the CB2 receptor. Increasing concentrations of Cannabis sativa (CS) induced A549 cell death in a time-dependent manner, followed by induction of early apoptosis, cell cycle arrest at sub G1 phase, elevation of ROS level, and activation of caspase 3. The CB2 blockage caused attenuation of CS effects on A549 cell death which revealed consistency with the effects of EP extract on A549 cells. Conclusions The pro-apoptotic effects of EP and CS extracts on A549 cells and their possible regulatory role of CB2 activity might be attributed to metabolites of both herbs. These effects deserve receiving more attention as alternative anti-cancer agents. Graphical abstract

scholarly journals Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
A549 Cell ◽  
P53 Protein ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Xenograft Tumor ◽  
Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

scholarly journals Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits growth of human lung cancer A549 cells by arresting cell cycle and triggering apoptosis

2012 ◽  
Vol 24 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Li Li ◽  
George G. Chen ◽  
Ying-nian Lu ◽  
Yi Liu ◽  
Ke-feng Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer

scholarly journals Propofol Inhibits Lung Cancer A549 Cell Growth and Epithelial‐Mesenchymal Transition Process by Upregulation of MicroRNA-1284

2018 ◽  
Vol 27 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Wei-Zhen Liu ◽  
Nian Liu
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
A549 Cell ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Foxm1 Expression

Propofol has been widely used in lung cancer resections. Some studies have demonstrated that the effects of propofol might be mediated by microRNAs (miRNAs). This study aimed to investigate the effects and mechanisms of propofol on lung cancer cells by regulation of miR-1284. A549 cells were treated with different concentrations of propofol, while transfected with miR-1284 inhibitor, si-FOXM1, and their negative controls. Cell viability, migration, and invasion, and the expression of miR-1284, FOXM1, and epithelial‐mesenchymal transition (EMT) factors were detected by CCK-8, Transwell, qRT-PCR, and Western blot assays, respectively. In addition, the regulatory and binding relationships among propofol, miR-1284, and FOXM1 were assessed, respectively. Results showed that propofol suppressed A549 cell viability, migration, and invasion, upregulated E-cadherin, and downregulated N-cadherin, vimentin, and Snail expressions. Moreover, propofol significantly promoted the expression of miR-1284. miR-1284 suppression abolished propofol-induced decreases of cell viability, migration, and invasion, and increased FOXM1 expression and the luciferase activity of FOXM1-wt. Further, miR-1284 negatively regulated FOXM1 expression. FOXM1 knockdown reduced cell viability, migration, and invasion by propofol treatment plus miR-1284 suppression. In conclusion, our study indicated that propofol could inhibit cell viability, migration, invasion, and the EMT process in lung cancer cells by regulation of miR-1284.

Sign in / Sign up

Export Citation Format

Share Document