scholarly journals Tempol Differently Affects Cellular Redox Status and Antioxidant Enzymes in Various Lung-related Cells

2021 ◽  
Author(s):  
woo hyun park
Keyword(s):  
Lung Cancer ◽  
Antioxidant Enzymes ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Annexin V ◽  
Redox Status ◽  
Normal Lung ◽  
Normal Cells ◽  
Cellular Redox ◽  
Protein Levels

Abstract Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a potential redox agent in cells. The present study investigated changes in cellular redox status [reactive oxygen species (ROS) and glutathione (GSH) levels] and in antioxidant enzymes, in Tempol-treated Calu-6 and A549 lung cancer cells, normal lung WI-38 VA-13 cells, and primary pulmonary fibroblasts. Results demonstrated that Tempol (0.5 ~ 4 mM) either increased or decreased general ROS levels in lung cancer and normal cells at 48 h and specifically increased O2•− levels in these cells. In addition, Tempol differentially altered the expression and activity of superoxide dismutase, catalase, and thioredoxin reductase1 (TrxR1) in A549, Calu-6, and WI-38 VA-13 cells. In particular, Tempol increased TrxR1 protein levels in these cells. Tempol at 1 mM inhibited the growth of lung cancer and normal cells by about 50% at 48 h but also significantly induced cell death, as evidenced by annexin V-positive cells. Furthermore, down-regulation of TrxR1 by siRNA somewhat affected the levels of cell growth inhibition and death as well as ROS in Tempol-treated cells. In addition, Tempol increased the numbers of GSH-depleted cells in both cancer cells and normal cells at 48h. In conclusion, Tempol differentially increased or decreased levels of ROS and various antioxidant enzymes in lung cancer and normal cells, and induced growth inhibition and death in all lung cells along with an increase in O2•− levels and GSH depletion.

scholarly journals Tempol differently affects cellular redox changes and antioxidant enzymes in various lung-related cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Woo Hyun Park
Keyword(s):  
Lung Cancer ◽  
Antioxidant Enzymes ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Annexin V ◽  
Normal Lung ◽  
Lung Cells ◽  
Normal Cells ◽  
Protein Levels ◽  
Cellular Reactive Oxygen Species

AbstractTempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a potential redox agent in cells. The present study investigated changes in cellular reactive oxygen species (ROS) and glutathione (GSH) levels and in antioxidant enzymes, in Tempol-treated Calu-6 and A549 lung cancer cells, normal lung WI-38 VA-13 cells, and primary pulmonary fibroblasts. Results demonstrated that Tempol (0.5–4 mM) either increased or decreased general ROS levels in lung cancer and normal cells at 48 h and specifically increased O2•− levels in these cells. In addition, Tempol differentially altered the expression and activity of antioxidant enzymes such as superoxide dismutase, catalase, and thioredoxin reductase1 (TrxR1) in A549, Calu-6, and WI-38 VA-13 cells. In particular, Tempol treatment increased TrxR1 protein levels in these cells. Tempol at 1 mM inhibited the growth of lung cancer and normal cells by about 50% at 48 h but also significantly induced cell death, as evidenced by annexin V-positive cells. Furthermore, down-regulation of TrxR1 by siRNA had some effect on ROS levels as well as cell growth inhibition and death in Tempol-treated or -untreated lung cells. In addition, some doses of Tempol significantly increased the numbers of GSH-depleted cells in both cancer cells and normal cells at 48 h. In conclusion, Tempol differentially increased or decreased levels of ROS and various antioxidant enzymes in lung cancer and normal cells, and induced growth inhibition and death in all lung cells along with an increase in O2•− levels and GSH depletion.

scholarly journals Functional polyesters enable selective siRNA delivery to lung cancer over matched normal cells

2016 ◽  
Vol 113 (39) ◽  
pp. E5702-E5710 ◽  
Author(s):  
Yunfeng Yan ◽  
Li Liu ◽  
Hu Xiong ◽  
Jason B. Miller ◽  
Kejin Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Drug Carrier ◽  
Sirna Delivery ◽  
Normal Lung ◽  
Cancer Therapies ◽  
Normal Cells ◽  
Alternative Approach ◽  
Dividing Cells

Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, we report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. Selective polyplex nanoparticles (NPs) were identified by high-throughput library screening on a unique pair of matched cancer/normal cell lines obtained from a single patient. Selective NPs promoted rapid endocytosis into HCC4017 cancer cells, but were arrested at the membrane of HBEC30-KT normal cells during the initial transfection period. When injected into tumor xenografts in mice, cancer-selective NPs were retained in tumors for over 1 wk, whereas nonselective NPs were cleared within hours. This translated to improved siRNA-mediated cancer cell apoptosis and significant suppression of tumor growth. Selective NPs were also able to mediate gene silencing in xenograft and orthotopic tumors via i.v. injection or aerosol inhalation, respectively. Importantly, this work highlights that different cells respond differentially to the same drug carrier, an important factor that should be considered in the design and evaluation of all NP carriers. Because no targeting ligands are required, these functional polyester NPs provide an exciting alternative approach for selective drug delivery to tumor cells that may improve efficacy and reduce adverse side effects of cancer therapies.

Differential effect of hypoxia and acidity on lung cancer cell and fibroblast metabolism

2017 ◽  
Vol 95 (3) ◽  
pp. 428-436 ◽  
Author(s):  
Alexandra Giatromanolaki ◽  
Maria Liousia ◽  
Stella Arelaki ◽  
Dimitra Kalamida ◽  
Stamatia Pouliliou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Metabolic Response ◽  
Expression Patterns ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Lung Cancer Cell ◽  
Protein Levels

This study examined the metabolic response of lung cancer cells and normal lung fibroblasts to hypoxia and acidity. GLUT1 and HXKII mRNA/protein expression was up-regulated under hypoxia in the MRC5 fibroblasts and in the A549 and H1299 lung cancer cell lines, indicating intensified glucose absorption and glycolysis. Under hypoxia, the LDHA mRNA and LDH5 protein levels increased in the cancer cells but not in the fibroblasts. Acidity suppressed the above-mentioned hypoxia effect. PDH-kinase-1 (PDK1 mRNA and protein) and inactive phosphorylated-PDH protein levels were induced under hypoxia in the cancer cells, whereas these were reduced in the MRC5 lung fibroblasts. In human tissue sections, the prevalent expression patterns supported the contrasting metabolic behavior of cancer cells vs. tumor fibroblasts. The monocarboxylate/lactate transporter 1 (MCT1) was up-regulated in all the cell lines under hypoxic conditions, but it was suppressed under acidic conditions. The mitochondrial DNA (mtDNA) content per cell decreased significantly in the A549 cancer cell line under hypoxia, but it increased in the MRC5 fibroblasts. Taking into account these findings, we suggest that, under hypoxia, cancer cells intensify the anaerobic direction in glycolysis, while normal fibroblasts prefer to seek energy by intensifying the aerobic use of the available oxygen.

Induction of p27KIP1 as a Mechanism Underlying NS398-Induced Growth Inhibition in Human Lung Cancer Cells

2000 ◽  
Vol 58 (6) ◽  
pp. 1398-1403 ◽  
Author(s):  
Wen-Chun Hung ◽  
Hui-Chiu Chang ◽  
Mei-Ren Pan ◽  
Te-Hsiu Lee ◽  
Lea-Yea Chuang
Keyword(s):  
Lung Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells

scholarly journals Micronutrients Selenomethionine and Selenocysteine Modulate the Redox Status of MCF-7 Breast Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 865 ◽  
Author(s):  
Daniel Gabriel Pons ◽  
Carmen Moran ◽  
Marina Alorda-Clara ◽  
Jordi Oliver ◽  
Pilar Roca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hydrogen Peroxide ◽  
Antioxidant Enzymes ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Redox Status ◽  
Hydrogen Peroxide Production ◽  
Low Concentrations ◽  
Mcf 7

Selenium is a micronutrient which is found in many foods, with redox status modulation activity. Our aim was to evaluate the effects of two chemical forms of selenoamino acids, Seleno-L-methionine and Seleno-L-cystine (a diselenide derived from selenocysteine), at different concentrations on cell viability, hydrogen peroxide production, antioxidant enzymes, UCP2 protein expression, as well as lipid and protein oxidative damage in MCF-7 breast cancer cells. Results showed that Seleno-L-methionine did not cause an increase in hydrogen peroxide production at relatively low concentrations, accompanied by a rise in the antioxidant enzymes catalase and MnSOD, and UCP2 protein expression levels. Furthermore, a decrease in protein and lipid oxidative damage was observed at 10 µM concentration. Otherwise, Seleno-L-cystine increased hydrogen peroxide production from relatively low concentrations (100 nM) to a large increase at high concentrations. Moreover, at 10 µM, Seleno-L-cystine decreased UCP2 and MnSOD protein expression. In conclusion, the chemical form of selenoamino acid and their incorporation to selenoproteins could affect the regulation of the breast cancer cell redox status. Taken together, the results obtained in this study imply that it is important to control the type of selenium-enriched nutrient consumption, taking into consideration their composition and concentration.

scholarly journals Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer

2020 ◽  
Vol 10 (3) ◽  
pp. 109 ◽  
Author(s):  
Hee Sung Chae ◽  
Minchan Gil ◽  
Subbroto Kumar Saha ◽  
Hee Jeung Kwak ◽  
Hwan-Woo Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Prognostic Value ◽  
Mammalian Target Of Rapamycin ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Lung Cancer Cells ◽  
Normal Lung ◽  
Therapeutic Modalities

Lung cancer remains the most dangerous type of cancer despite recent progress in therapeutic modalities. Development of prognostic markers and therapeutic targets is necessary to enhance lung cancer patient survival. Sestrin family genes (Sestrin1, Sestrin2, and Sestrin3) are involved in protecting cells from stress. In particular, Sestrin2, which mainly protects cells from oxidative stress and acts as a leucine sensor protein in mammalian target of rapamycin (mTOR) signaling, is thought to affect various cancers in different ways. To investigate the role of Sestrin2 expression in lung cancer cells, we knocked down Sestrin2 in A549, a non-small cell lung cancer cell line; this resulted in reduced cell proliferation, migration, sphere formation, and drug resistance, suggesting that Sestrin2 is closely related to lung cancer progression. We analyzed Sestrin2 expression in human tissue using various bioinformatic databases and confirmed higher expression of Sestrin2 in lung cancer cells than in normal lung cells using Oncomine and the Human Protein Atlas. Moreover, analyses using Prognoscan and KMplotter showed that Sestrin2 expression is negatively correlated with the survival of lung cancer patients in multiple datasets. Co-expressed gene analysis revealed Sestrin2-regulated genes and possible associated pathways. Overall, these data suggest that Sestrin2 expression has prognostic value and that it is a possible therapeutic target in lung cancer.

scholarly journals N-ω-chloroacetyl-l-ornithine, a new competitive inhibitor of ornithine decarboxylase, induces selective growth inhibition and cytotoxicity on human cancer cells versus normal cells

2014 ◽  
Vol 30 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Miriam Marlene Medina-Enríquez ◽  
Verónica Alcántara-Farfán ◽  
Leopoldo Aguilar-Faisal ◽  
José Guadalupe Trujillo-Ferrara ◽  
Lorena Rodríguez-Páez ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Cancer Cells ◽  
Ornithine Decarboxylase ◽  
Human Cancer ◽  
Competitive Inhibitor ◽  
Selective Growth ◽  
Normal Cells ◽  
Human Cancer Cells

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 Gene interfered-ferroptosis therapy for cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinliang Gao ◽  
Tao Luo ◽  
Jinke Wang
Keyword(s):  
Drug Resistance ◽  
Cancer Therapy ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Iron Nanoparticles ◽  
Tumor Growth Inhibition ◽  
Specific Gene ◽  
Normal Cells ◽  
Adeno Associated Virus ◽  
Metabolic Genes

AbstractAlthough some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis.

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