scholarly journals Gene Expression Profile of the A549 Human Non-Small Cell Lung Carcinoma Cell Line following Treatment with the Seeds ofDescurainia sophia, a Potential Anticancer Drug

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Bu-Yeo Kim ◽  
Jun Lee ◽  
Sung Joon Park ◽  
Ok-Sun Bang ◽  
No Soo Kim
Keyword(s):  
Gene Expression ◽  
Cancer Cells ◽  
Human Cancer ◽  
Small Cell Lung Carcinoma ◽  
Ethanol Extract ◽  
Inhibitory Effect ◽  
Human Lung Cancer ◽  
Molecular Evidence ◽  
Cell Lung Carcinoma ◽  
Dose Dependent

Descurainia sophiahas been traditionally used in Korean medicine for treatment of diverse diseases and their symptoms, such as cough, asthma, and edema. Our previous results showed that ethanol extract of the seeds ofD. sophia(EEDS) has a potent cytotoxic effect on human cancer cells. In this study, we reveal the molecular events that are induced by EEDS treatment in A549 human lung cancer cells. The dose-dependent effect of EEDS on gene expression was measured via a microarray analysis. Gene ontology and pathway analyses were performed to identify functional involvement of genes regulated by EEDS. From gene expression analyses, two major dose-dependent patterns were observed after EEDS treatment. One pattern consisted of 1,680 downregulated genes primarily involved in metabolic processes (FDR < 0.01). The second pattern consisted of 1,673 upregulated genes primarily involved in signaling processes (FDR < 0.01). Pathway activity analyses revealed that the metabolism-related pathways and signaling-related pathways were regulated by the EEDS in dose-dependent and reciprocal manners. In conclusion, the identified biphasic regulatory mechanism involving activation of signaling pathways may provide molecular evidence to explain the inhibitory effect of EEDS on A549 cell growth.

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 A Potent Autophagy Inhibitor (Lys05) Enhances the Impact of Ionizing Radiation on Human Lung Cancer Cells H1299

2019 ◽  
Vol 20 (23) ◽  
pp. 5881 ◽  
Author(s):  
Lucie Cechakova ◽  
Martin Ondrej ◽  
Vojtech Pavlik ◽  
Petr Jost ◽  
Dana Cizkova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Small Cell Lung Carcinoma ◽  
Combined Treatment ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cell Lung Carcinoma ◽  
The Impact ◽  
Autophagy Inhibition

Autophagy inhibition through small-molecule inhibitors is one of the approaches to increase the efficiency of radiotherapy in oncological patients. A new inhibitor—Lys05—with the potential to accumulate within lysosomes and to block autophagy was discovered a few years ago. Several studies have addressed its chemosensitizing effects but nothing is known about its impact in the context of ionizing radiation (IR). To describe its role in radiosensitization, we employed radioresistant human non-small cell lung carcinoma cells (H1299, p53-negative). Combined treatment of H1299 cells by Lys05 together with IR decreased cell survival in the clonogenic assay and real-time monitoring of cell growth more than either Lys05 or IR alone. Immunodetection of LC3 and p62/SQSTM1 indicated that autophagy was inhibited, which correlated with increased SQSTM1 and decreased BNIP3 gene expression determined by qRT-PCR. Fluorescence microscopy and flow cytometry uncovered an accumulation of lysosomes. Similarly, transmission electron microscopy demonstrated the accumulation of autophagosomes confirming the ability of Lys05 to potentiate autophagy inhibition in H1299 cells. We report here for the first time that Lys05 could be utilized in combination with IR as a promising future strategy in the eradication of lung cancer cells.

scholarly journals Anti-inflammatory role of curcumin in Lipopolysaccharide treated A549 cells at global proteome level and on mycobacterial infection

2019 ◽  
Author(s):  
Suchita Singh ◽  
Rakesh Arya ◽  
Rhishikesh R Bargaje ◽  
Mrinal Kumar Das ◽  
Subia Akram ◽  
...  
Keyword(s):  
Isotope Labeling ◽  
Small Cell Lung Carcinoma ◽  
Bacterial Load ◽  
Critical Role ◽  
A549 Cells ◽  
Molecular Evidence ◽  
Simultaneous Treatment ◽  
Cell Lung Carcinoma ◽  
Anti Inflammatory

AbstractA diet derived agent Curcumin (Diferuloylmethane), demonstrated its clinical application in inflammation, infection and cancer conditions. Nevertheless, its impact on the proteome of epithelial cells of non-small cell lung carcinoma (NSCLC) is yet to be explored. We employed a stable isotope labeling method for cell culture (SILAC) based relative quantitative proteomics and informatics analysis to comprehend global proteome change in A549 cells treated with curcumin and/or Lipopolysaccharide (LPS). Pretreated A549 cells were infected with Mycobacterium tuberculosis H37Rv strain to monitor bacterial load. With exposure to curcumin and LPS, out of the 1492 identified proteins, 305 and 346 proteins showed deregulation respectively. The expression of BID and AIFM1 mitochondrial proteins which play critical role in apoptotic pathway were deregulated in curcumin treated cells. Higher mitochondria intensity was observed in curcumin treated A549 cells than LPS treatment. Simultaneous treatment of curcumin and LPS neutralized the effect of LPS. Curcumin and/or LPS pretreated A549 cells infected with H37Rv, showed successful bacterial internalization. LPS treated A549 cells after infection showed increased bacterial load than curcumin compared to non-treated infected cells. However, simultaneous treatment of curcumin and LPS neutralized the effect of LPS. This study generated molecular evidence to deepen our understanding of the anti-inflammatory role of curcumin and may be useful to identify molecular targets for drug discovery.

scholarly journals The Study of Anticancer Activity of Satureja Khuzestanica Alcoholic Extracts On Expression of Bcl2 And Bax Genes In The Pc3 Cell Line

2021 ◽  
Author(s):  
Saman Kazemi ◽  
asghar tanomand ◽  
Hossein Soltanzadeh ◽  
Gholamreza Shahsavari
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Cells ◽  
Rna Extraction ◽  
Inhibitory Effect ◽  
Chloroform Extract ◽  
Antioxidant Compounds ◽  
Anticancer Properties ◽  
Satureja Khuzestanica ◽  
Induced Apoptosis

Abstract Introduction: Prostate cancer is the most common cancer among men after lung cancer. It has grown in Iran in recent years. The use of medicinal plants is one of the most useful ways that causes the least side effects. Due to high levels of antioxidant compounds, Satureja khuzestanica is a good source for drug use to treat and prevent the development and progress of cancers. The aim of the present study was to evaluate the anti-cancer property of Satureja khuzestanica extract on the expression of Bcl2 and Bax genes in prostate cancer cell lines.Methodology: After collecting the plant in spring, the chloroform extract was prepared by rotary device. PC3 cancer cells were incubated at different concentrations of the extract for 24 hours. The inhibitory effect of the extract was evaluated using MTT assay as IC50. To evaluate apoptosis, the level of expression of Bax and BCL-2 genes after RNA extraction and transformation to cDNA were evaluated using Real Time PCR. All data were analyzed using REST software.Results: The results revealed a direct and significant relationship between the two variables of drug composition and rate of PC3 cell death. This composition increased Bax gene expression and decreased BCL-2 gene expression and induced apoptosis (P <0.05).Discussion and Conclusion: Based on the results, Satureja khuzestanica extract is likely to have anticancer properties and seems to be a new drug for killing prostate cancer cells.

scholarly journals Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaokun Wang ◽  
Dongjuan Qiao ◽  
Likun Chen ◽  
Meng Xu ◽  
Shupeng Chen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Small Cell Lung Carcinoma ◽  
Underlying Mechanism ◽  
Chemotherapeutic Agents ◽  
Chemotherapeutic Drugs ◽  
Xenograft Tumor ◽  
Tumor Models ◽  
Cell Lung Carcinoma

Abstract Background Chemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles (EVs) mediate MDR, but the underlying mechanism remains unclear, especially the effects of chemotherapeutic agents on this process. Methods Extracellular vesicles isolation was performed by differential centrifugation. The recipient cells that acquired ATP-binding cassette sub-family B member 1 (ABCB1) proteins were sorted out from co-cultures according to a stringent multi-parameter gating strategy by fluorescence-activated cell sorting (FACS). The transfer rate of ABCB1 was measured by flow cytometry. The xenograft tumor models in mice were established to evaluate the transfer of ABCB1 in vivo. Gene expression was detected by real-time PCR and Western blotting. Results Herein, we show that a transient exposure to chemotherapeutic agents can strikingly increase Rab8B-mediated release of extracellular vesicles (EVs) containing ABCB1 from drug-resistant cells, and accelerate these EVs to circulate back onto plasma membrane of sensitive tumor cells via the down-regulation of Rab5. Therefore, intercellular ABCB1 transfer is significantly enhanced; sensitive recipient cells acquire a rapid but unsustainable resistance to evade the cytotoxicity of chemotherapeutic agents. More fascinatingly, in the xenograft tumor models, chemotherapeutical drugs also locally or distantly increase the transfer of ABCB1 molecules. Furthermore, some Non-small-cell lung carcinoma (NSCLC) patients who are undergoing primary chemotherapy have a rapid increase of ABCB1 protein in their monocytes, and this is obviously associated with poor chemotherapeutic efficacy. Conclusions Chemotherapeutic agents stimulate the secretion and recycling of ABCB1-enriched EVs through the dysregulation of Rab8B and Rab5, leading to a significant increase of ABCB1 intercellular transfer, thus assisting sensitive cancer cells to develop an urgent resistant phenotype. Our findings provide a new molecular mechanism of how chemotherapeutic drugs assist sensitive cancer cells in acquiring an urgent resistance.

scholarly journals The Marine Dinoflagellate Alexandrium minutum Activates a Mitophagic Pathway in Human Lung Cancer Cells

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 502 ◽  
Author(s):  
Christian Galasso ◽  
Genoveffa Nuzzo ◽  
Christophe Brunet ◽  
Adrianna Ianora ◽  
Angela Sardo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Water Soluble ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Normal Lung ◽  
Alexandrium Minutum ◽  
Human Lung Cancer Cells

Marine dinoflagellates are a valuable source of bioactive molecules. Many species produce cytotoxic compounds and some of these compounds have also been investigated for their anticancer potential. Here, we report the first investigation of the toxic dinoflagellate Alexandrium minutum as source of water-soluble compounds with antiproliferative activity against human lung cancer cells. A multi-step enrichment of the phenol–water extract yielded a bioactive fraction with specific antiproliferative effect (IC50 = 0.4 µg·mL−1) against the human lung adenocarcinoma cells (A549 cell line). Preliminary characterization of this material suggested the presence of glycoprotein with molecular weight above 20 kDa. Interestingly, this fraction did not exhibit any cytotoxicity against human normal lung fibroblasts (WI38). Differential gene expression analysis in A549 cancer cells suggested that the active fraction induces specific cell death, triggered by mitochondrial autophagy (mitophagy). In agreement with the cell viability results, gene expression data also showed that no mitophagic event was activated in normal cells WI38.

scholarly journals GLUL Ablation Can Confer Drug Resistance to Cancer Cells via a Malate-Aspartate Shuttle-Mediated Mechanism

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1945
Author(s):  
Magesh Muthu ◽  
Ranjeet Kumar ◽  
Azharuddin Sajid Syed Khaja ◽  
Jonathan D. Gilthorpe ◽  
Jenny L. Persson ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Cancer Drug ◽  
Aminooxyacetic Acid ◽  
Cell Lung Carcinoma ◽  
Metabolic Fitness ◽  
Malate Aspartate Shuttle

Glutamate-ammonia ligase (GLUL) is important for acid-base homeostasis, ammonia detoxification, cell signaling, and proliferation. Here, we reported that GLUL ablation conferred resistance to several anticancer drugs in specific cancer cell lines while leaving other cell lines non-resistant to the same drugs. To understand the biochemical mechanics supporting this drug resistance, we compared drug-resistant GLUL knockout (KO) A549 non-small-cell lung carcinoma (NSCLC) cells with non-resistant GLUL KO H1299 NSCLC cells and found that the resistant A549 cells, to a larger extent, depended on exogenous glucose for proliferation. As GLUL activity is linked to the tricarboxylic acid (TCA) cycle via reversed glutaminolysis, we probed carbon flux through both glycolysis and TCA pathways by means of 13C5 glutamine, 13C5 glutamate, and 13C6 glucose tracing. We observed increased labeling of malate and aspartate in A549 GLUL KO cells, whereas the non-resistant GLUL KO H1299 cells displayed decreased 13C-labeling. The malate and aspartate shuttle supported cellular NADH production and was associated with cellular metabolic fitness. Inhibition of the malate-aspartate shuttle with aminooxyacetic acid significantly impacted upon cell viability with an IC50 of 11.5 μM in resistant GLUL KO A549 cells compared to 28 μM in control A549 cells, linking resistance to the malate-aspartate shuttle. Additionally, rescuing GLUL expression in A549 KO cells increased drug sensitivity. We proposed a novel metabolic mechanism in cancer drug resistance where the increased capacity of the malate-aspartate shuttle increased metabolic fitness, thereby facilitating cancer cells to escape drug pressure.

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