scholarly journals Mitochondria-Targeted Antioxidants MitoQ and MitoTEMPO Do Not Influence BRAF-Driven Malignant Melanoma and KRAS-Driven Lung Cancer Progression in Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Kristell Le Gal ◽  
Clotilde Wiel ◽  
Mohamed X. Ibrahim ◽  
Marcus Henricsson ◽  
Volkan I. Sayin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Malignant Melanoma ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Nuclear Dna ◽  
Human Melanoma ◽  
Oxygen Species ◽  
Lung Cancer Cell ◽  
Primary Tumors ◽  
Anti Cancer

Cancer cells produce high levels of mitochondria-associated reactive oxygen species (ROS) that can damage macromolecules, but also promote cell signaling and proliferation. Therefore, mitochondria-targeted antioxidants have been suggested to be useful in anti-cancer therapy, but no studies have convincingly addressed this question. Here, we administered the mitochondria-targeted antioxidants MitoQ and MitoTEMPO to mice with BRAF-induced malignant melanoma and KRAS-induced lung cancer, and found that these compounds had no impact on the number of primary tumors and metastases; and did not influence mitochondrial and nuclear DNA damage levels. Moreover, MitoQ and MitoTEMPO did not influence proliferation of human melanoma and lung cancer cell lines. MitoQ and its control substance dTPP, but not MitoTEMPO, increased glycolytic rates and reduced respiration in melanoma cells; whereas only dTPP produced this effect in lung cancer cells. Our results do not support the use of mitochondria-targeted antioxidants for anti-cancer monotherapy, at least not in malignant melanoma and lung cancer.

scholarly journals Mesoporous silica particles functionalized with newly extracted fish oil (Omeg@Silica) inhibit lung cancer cell growth

Nanomedicine ◽  
2021 ◽  
Vol 16 (23) ◽  
pp. 2061-2074
Author(s):  
Caterina Di Sano ◽  
Claudia D’Anna ◽  
Antonino Scurria ◽  
Claudia Lino ◽  
Mario Pagliaro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Mesoporous Silica ◽  
Fish Oil ◽  
Cancer Cells ◽  
Oxygen Species ◽  
Lung Cancer Cell ◽  
Antitumor Effects ◽  
Silica Microparticles

Aim: To assess whether Omeg@Silica microparticles – fish oil from anchovy fillet leftovers (AnchoisOil) encapsulated within mesoporous silica particles – are effective in promoting antitumor effects in lung cancer cells. Methods: Three human non-small-cell lung cancer cell lines (A549, Colo 699 and SK-MES-1) were used. Cells were treated with AnchoisOil dispersed in ethanol (10 and 15 μg/ml) or encapsulated in silica and further formulated in aqueous ethanol. Cell cycle, reactive oxygen species, mitochondrial stress and long-term proliferation were assessed. Results & conclusion: Omeg@Silica microparticles were more effective than fish oil in increasing reactive oxygen species and mitochondrial damage, and in altering the cell cycle and reducing cell proliferation, in lung cancer cells. These in vitro antitumor effects of Omeg@Silica support its investigation in lung cancer therapy.

scholarly journals Microfluidic Single-Cell Proteomics Assay Chip: Lung Cancer Cell Line Case Study

Micromachines ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1147
Author(s):  
Yugyung Jung ◽  
Minkook Son ◽  
Yu Ri Nam ◽  
Jongchan Choi ◽  
James R. Heath ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Cancer Drugs ◽  
Lung Cancer Cell ◽  
Anti Cancer

Cancer is a dynamic disease involving constant changes. With these changes, cancer cells become heterogeneous, resulting in varying sensitivity to chemotherapy. The heterogeneity of cancer cells plays a key role in chemotherapy resistance and cancer recurrence. Therefore, for effective treatment, cancer cells need to be analyzed at the single-cell level by monitoring various proteins and investigating their heterogeneity. We propose a microfluidic chip for a single-cell proteomics assay that is capable of analyzing complex cellular signaling systems to reveal the heterogeneity of cancer cells. The single-cell assay chip comprises (i) microchambers (n = 1376) for manipulating single cancer cells, (ii) micropumps for rapid single-cell lysis, and (iii) barcode immunosensors for detecting nine different secretory and intracellular proteins to reveal the correlation among cancer-related proteins. Using this chip, the single-cell proteomics of a lung cancer cell line, which may be easily masked in bulk analysis, were evaluated. By comparing changes in the level of protein secretion and heterogeneity in response to combinations of four anti-cancer drugs, this study suggests a new method for selecting the best combination of anti-cancer drugs. Subsequent preclinical and clinical trials should enable this platform to become applicable for patient-customized therapies.

scholarly journals MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good?

2017 ◽  
Author(s):  
Hussein H.K. Abbas ◽  
Kheloud M.H. Alhamoudi ◽  
Mark D. Evans ◽  
George D.D. Jones ◽  
Steven S. Foster
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Oxidative Dna Damage ◽  
Dna Oxidation ◽  
Oxygen Species ◽  
Lung Cancer Cell

AbstractBackgroundTargeted therapies are based on exploiting cancer-cell-specific genetic features or phenotypic traits to selectively kill cancer cells while leaving normal cells unaffected. Oxidative stress is a cancer hallmark phenotype. Given that free nucleotide pools are particularly vulnerable to oxidation, the nucleotide pool sanitising enzyme, MTH1, is potentially conditionally essential in cancer cells. However, findings from previous MTH1 studies have been contradictory, meaning the relevance of MTH1 in cancer is still to be determined. Here we ascertained the role of MTH1 specifically in lung cancer cell maintenance, and the potential of MTH1 inhibition as a targeted therapy strategy to improve lung cancer treatments.MethodUsing siRNA-mediated knockdown or small-molecule inhibition, we tested the genotoxic and cytotoxic effects of MTH1 deficiency on H23 (p53-mutated), H522 (p53-mutated) and A549 (wildtype p53) non-small cell lung cancer cell lines relative to normal MRC-5 lung fibroblasts. We also assessed if MTH1 inhibition augments current therapies.ResultsMTH1 knockdown increased levels of oxidatively damaged DNA and DNA damage signaling alterations in all lung cancer cell lines but not normal fibroblasts, despite no detectable differences in reactive oxygen species levels between any cell lines. Furthermore, MTH1 knockdown reduced H23 cell proliferation. However, unexpectedly, it did not induce apoptosis in any cell line or enhance the effects of gemcitabine, cisplatin or radiation in combination treatments. Contrastingly, TH287 and TH588 MTH1 inhibitors induced apoptosis in H23 and H522 cells, but only increased oxidative DNA damage levels in H23, indicating that they kill cells independently of DNA oxidation and seemingly via MTH1-distinct mechanisms.ConclusionsMTH1 has a NSCLC-specific p53-independent role for suppressing DNA oxidation and genomic instability, though surprisingly the basis of this may not be reactive-oxygen-species-associated oxidative stress. Despite this, overall our cell viability data indicates that targeting MTH1 will likely not be an across-the-board effective NSCLC therapeutic strategy; rather it induces non-cytotoxic DNA damage that could promote cancer heterogeneity and evolution.

Exosomal lncRNA FOXD3-AS1 upregulates ELAVL1 expression and activates PI3K/Akt pathway to enhance lung cancer cell proliferation, invasion, and 5-fluorouracil resistance

2021 ◽  
Author(s):  
Guangxian Mao ◽  
Zhimin Mu ◽  
Da Wu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
A549 Cells ◽  
Akt Pathway ◽  
Lung Cancer Cell

Abstract Long non-coding RNA (lncRNA) FOXD3-AS1 expression is upregulated in lung cancer; however, its effect and mechanism on 5-fluorouracil (5-FU) resistance remain unclear. In this study, we determined the effects of FOXD3-AS1-enriched exosomes derived from lung cancer cells on the proliferation, invasion, and 5-FU resistance of lung cancer cells. Online bioinformatics database analysis showed that FOXD3-AS1 was upregulated in lung cancer progression. Real-time quantitative PCR results confirmed that FOXD3-AS1 expression was upregulated in lung cancer tissues and cell lines, and FOXD3-AS1 was greatly enriched in lung cancer cell-derived exosomes. ELAV-like RNA-binding protein 1 (ELAVL1) was identified as an RNA-binding protein of FOXD3-AS1. The lung cancer cell-derived exosomes promoted A549 cell proliferation and invasion and inhibited apoptosis caused by 5-FU, and transfection of si-FOXD3-AS1 or si-ELAVL1 in exosome-incubated A549 cells reversed these effects. Moreover, exosome-incubated A549 cells were co-transfected with si-FOXD3-AS1 and pcDNA-ELAVL1, showing the same cell proliferation, invasion, and 5-FU resistance as those of A549 cells treated with lung cancer cell-derived exosomes alone. Mechanistic studies identified that lung cancer cell-derived exosomes activated the PI3K/Akt pathway, and transfection of si-FOXD3-AS1 or treatment with the PI3K inhibitor LY294002 reversed the activation of the PI3K/Akt axis induced by exosomes. In conclusion, our study revealed that lung cancer cell-derived exosomal FOXD3-AS1 upregulated ELAVL1 expression and activated the PI3K/Akt pathway to promote lung cancer progression. Our findings provide a new strategy for lung cancer treatment.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

scholarly journals 2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

Biosensors ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 40
Author(s):  
Mahek Sadiq ◽  
Lizhi Pang ◽  
Michael Johnson ◽  
Venkatachalem Sathish ◽  
Qifeng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Small Cell ◽  
Gas Chromatography Mass Spectrometry ◽  
High Signal ◽  
Research Attention ◽  
Lung Cancer Treatment ◽  
Anti Cancer ◽  
Cox 2

Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related deaths among both men and women around the world. A lot of research attention has been directed toward diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (cyclooxygenase-2) inhibitors. This is because COX-2 is commonly overexpressed in lung cancer and also the abundance of its enzymatic product prostaglandin E2 (PGE2). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we introduce a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6) fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX-2 expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di does not only limit the metabolic product, PGE2, but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE2 and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. In this paper, we mainly report on a novel sensor, which is based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, or Ti3C2 MXene. The preliminary results have proven to sensitively, selectively, precisely, and effectively detect PGE2 and 8-HOA in A549 lung cancer cells. The capability of the sensor to detect trace level 8-HOA in A549 has been verified in comparison with the traditional gas chromatography–mass spectrometry (GC–MS) method. The sensing principle could be due to the unique structure and material property of Ti3C2 MXene: a multilayered structure and extremely large surface area, metallic conductivity, and ease and versatility in surface modification. All these make the Ti3C2 MXene-based sensor selectively adsorb 8-HOA molecules through effective charge transfer and lead to a measurable change in the conductivity of the material with a high signal-to-noise ratio and excellent sensitivity.

scholarly journals Magnetic tri-bead microrobot assisted near-infrared triggered combined photothermal and chemotherapy of cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoxia Song ◽  
Zhi Chen ◽  
Xue Zhang ◽  
Junfeng Xiong ◽  
Teng Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Stimuli Responsive ◽  
Lung Cancer Cell ◽  
Precise Movement ◽  
Photothermal Property

AbstractMagnetic micro/nanorobots attracted much attention in biomedical fields because of their precise movement, manipulation, and targeting abilities. However, there is a lack of research on intelligent micro/nanorobots with stimuli-responsive drug delivery mechanisms for cancer therapy. To address this issue, we developed a type of strong covalently bound tri-bead drug delivery microrobots with NIR photothermal response azobenzene molecules attached to their carboxylic surface groups. The tri-bead microrobots are magnetic and showed good cytocompatibility even when their concentration is up to 200 µg/mL. In vitro photothermal experiments demonstrated fast NIR-responsive photothermal property; the microrobots were heated to 50 °C in 4 min, which triggered a significant increase in drug release. Motion control of the microrobots inside a microchannel demonstrated the feasibility of targeted therapy on tumor cells. Finally, experiments with lung cancer cells demonstrated the effectiveness of targeted chemo-photothermal therapy and were validated by cell viability assays. These results indicated that tri-bead microrobots have excellent potential for targeted chemo-photothermal therapy for lung cancer cell treatment.

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