scholarly journals Annexin a2 as a target protein for chlorogenic acid in human lung cancer A549 cells

2020 ◽  
Author(s):  
Lei Wang ◽  
Hongwu Du ◽  
Peng Chen
Keyword(s):  
Chlorogenic Acid ◽  
Covalent Binding ◽  
Animal Experiments ◽  
A549 Cells ◽  
Annexin A2 ◽  
Human Lung Cancer ◽  
Target Proteins ◽  
Apoptotic Genes

AbstractChlorogenic acid, an important active component of coffee with anti-tumor activities, has been found for many years. However, the lack of understanding about its target proteins greatly limits the exploration of its anti-tumor molecular mechanism and clinical application. Here, in vitro and animal experiments showed that chlorogenic acid had a significant inhibitory effect on the proliferation of A549 cells. Using the spontaneous fluorescence characteristic of chlorogenic acid to screen the target proteins cleverly to avoid the problem of chemical modification increasing false positive, we identify and verify annexin A2 (ANXA2) as a covalent binding target of chlorogenic acid in A549 cells. Then, we discover that chlorogenic acid as an inhibitor of the binding of ANXA2 to p50 subunit inhibited the expression of downstream anti-apoptotic genes cIAP1 and cIAP2 of NF-κB signaling pathway in A549 cells in vitro and vivo. Moreover, we find chlorogenic acid hindered the binding of ANXA2 and actin maybe involved in the impediment of tumor cell cycle and migration. Thus, this work demonstrates that chlorogenic acid, as a binding ligand of ANXA2, decrease the expression of NF-κB downstream anti-apoptotic genes, inhibiting the proliferation of A549 cells in vivo and vitro.

scholarly journals Molecular Role of EGFR-MAPK Pathway in Patchouli Alcohol-Induced Apoptosis and Cell Cycle Arrest on A549 CellsIn VitroandIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
XinGang Lu ◽  
Liu Yang ◽  
ChengHua Lu ◽  
ZhenYu Xu ◽  
HongFu Qiu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mapk Pathway ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Activity Measurement ◽  
Cover Glass ◽  
Patchouli Alcohol ◽  
Pogostemon Cablin

Nowadays, chemotherapy is still the main effective treatment for cancer. Herb prescriptions containingPogostemon cablin Benth(also known as “Guang-Huo-Xiang”) have been widely used in Chinese medicine today. In our research, we found that patchouli alcohol, a compound isolated from the oil ofPogostemon cablin Benth, exerted antitumor ability against human lung cancer A549 cells ability bothin vitroandin vivo. MTT assay was used to assess cell viability. Hoechst 33342 staining and TUNEL cover glass staining provided the visual evidence of apoptosis. Caspase activity measurement showed that patchouli alcohol activated caspase 9 and caspase 3 of mitochondria-mediated apoptosis. Consistently, patchouli alcohol inhibited the xenograft tumorin vivo. Further investigation of the underlying molecular mechanism showed that MAPK and EGFR pathway might contribute to the antitumor effect of patchouli alcohol. Our study proved that patchouli alcohol might be able to serve as a novel antitumor compound in the clinical treatment of lung cancer.

scholarly journals Lipopolysaccharide administration alters extracellular vesicles in human lung-cancer cells and mice

2020 ◽  
Author(s):  
Leandra B. Jones ◽  
Sanjay Kumar ◽  
Courtnee’ R. Bell ◽  
Brennetta J. Crenshaw ◽  
Mamie T. Coats ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Bacterial Infection ◽  
Cell Line ◽  
Extracellular Vesicles ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Diagnostic Tools ◽  
The Impact

AbstractExtracellular vesicles (EVs) play a fundamental role in cell and infection biology and have the potential to act as biomarkers for novel diagnostic tools. In this study, we explored the in vitro impact of bacterial lipopolysaccharide administration on a cell line that represents a target for bacterial infection in the host. Administration of lipopolysaccharide at varying concentrations to this A549 cell line caused only modest changes in cell death, but EV numbers were significantly changed. After treatment with the highest concentration of lipopolysaccharide, EVs derived from A549 cells packaged significantly less interleukin-6 and lysosomal-associated membrane protein 1. We also examined the impact of lipopolysaccharide administration on exosome biogenesis and cargo composition in BALB/c mice. Serum-isolated EVs from lipopolysaccharide-treated mice showed significantly increased lysosomal-associated membrane protein 1 and toll-like receptor 4 levels compared with EVs from control mice. In summary, this study demonstrated that EV numbers and cargo were altered using these in vitro and in vivo models of bacterial infection.

scholarly journals Essential role of p21/waf1 in the mediation of the anti-proliferative effects of GHRH antagonist JMR-132

2008 ◽  
Vol 41 (5) ◽  
pp. 389-392 ◽  
Author(s):  
Aspasia-Athina Volakaki ◽  
Daniel Lafkas ◽  
Eva Kassi ◽  
Andrew V Schally ◽  
Athanasios G Papavassiliou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanism ◽  
A549 Cells ◽  
Significant Inhibition ◽  
Human Lung Cancer ◽  
Dependent Manner ◽  
Ghrh Antagonists ◽  
P21 Waf1

GHRH, besides its neuroendocrine action in controlling the release of GH from the pituitary, stimulates the growth of various cancers in vivo and in vitro by direct mechanism(s). However, the molecular mechanism that mediates these proliferative effects of GHRH in extrapituitary tissues remains poorly characterized. In the present study, we investigated whether the tumor suppressor p21/waf1 is involved in the mediation of the proliferative effects of GHRH in A549 human lung cancer epithelial cells. Exposure of A549 cells to the GHRH antagonist JMR-132 caused a significant inhibition in the rate of cell proliferation. In A549 cells, GHRH suppressed while JMR-132 increased the levels of p21 expression in a dose-dependent manner. This suggests that GHRH could regulate p21 levels. We then evaluated whether p21 is required in A549 cells for the regulation of cell proliferation by GHRH. To this end, we knocked-down p21 expression in A549 cells by siRNA and assessed the effects of antagonist JMR-132 on cell proliferation. We found that the loss of p21 expression abolished the anti-proliferative effects of JMR-132. Suppression of p21 expression by siRNA in human HT29 colon cancer cells and non-transformed mouse osteoblasts KS483 also blocked the anti-proliferative effects of JMR-132 suggesting that the regulation of cell proliferation by GHRH is p21 dependent. These results shed light on the molecular mechanism of action of GHRH antagonists in tumor tissues and suggest that the antineoplastic activity of GHRH antagonists could be considered for the treatment of cancers expressing p21.

In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells

2006 ◽  
Vol 72 (3) ◽  
pp. 308-319 ◽  
Author(s):  
Yi-Lin Chen ◽  
Shinn-Zong Lin ◽  
Jang-Yang Chang ◽  
Yeung-Leung Cheng ◽  
Nu-Man Tsai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Anticancer Agent ◽  
Human Lung ◽  
A549 Cells ◽  
In Vivo Studies ◽  
Human Lung Cancer

scholarly journals Antiangiogenesis-Combined Photothermal Therapy in the Second Near-Infrared Window at Laser Powers Below the Skin Tolerance Threshold

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Jian-Li Chen ◽  
Han Zhang ◽  
Xue-Qin Huang ◽  
Hong-Ye Wan ◽  
Jie Li ◽  
...  
Keyword(s):  
Laser Irradiation ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
A549 Cells ◽  
In Vivo Studies ◽  
Human Lung Cancer ◽  
Strong Light ◽  
Therapy Strategy

Abstract Photothermal agents with strong light absorption in the second near-infrared (NIR-II) region (1000–1350 nm) are strongly desired for successful photothermal therapy (PTT). In this work, titania-coated Au nanobipyramids (NBP@TiO2) with a strong plasmon resonance in the NIR-II window were synthesized. The NBP@TiO2 nanostructures have a high photothermal conversion efficiency of (93.3 ± 5.2)% under 1064-nm laser irradiation. They are also capable for loading an anticancer drug combretastatin A-4 phosphate (CA4P). In vitro PTT studies reveal that 1064-nm laser irradiation can efficiently ablate human lung cancer A549 cells and enhance the anticancer effect of CA4P. Moreover, the CA4P-loaded NBP@TiO2 nanostructures combined with PTT induce a synergistic antiangiogenesis effect. In vivo studies show that such CA4P-loaded NBP@TiO2 nanostructures under mild 1064-nm laser irradiation at an optical power density of 0.4 W cm−2, which is lower than the skin tolerance threshold value, exhibit a superior antitumor effect. This work presents not only the development of the NBP@TiO2 nanostructures as a novel photothermal agent responsive in the NIR-II window but also a unique combined chemo-photothermal therapy strategy for cancer therapy.

Targeted Photodynamic Therapy (PDT) of Lung Cancer with Biotinylated Silicon (IV) Phthalocyanine.

2020 ◽  
Vol 21 ◽  
Author(s):  
Wenyi Dong ◽  
Ke Li ◽  
Shijie Wang ◽  
Ling Qiu ◽  
Qingzhu Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Imaging System ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
In Vitro Assays ◽  
Cancer Therapies ◽  
Lung Cancers

Background: Lung cancer is the leading cause of cancer-associated mortality in the world. Traditional cancer therapies prolong life expectancy of patients but often suffer from adverse reactions. Photodynamic therapy (PDT) has been recommended as a treatment option for lung cancer in several countries, due to its non-invasive procedures, high selectivity and weak side effects. Objective: We have designed and synthesized a biotin receptor-targeted silicon phthalocyanine (IV) (compound 1) which showed good therapeutic effect on biotin receptor-positive tumors. Since the overexpression of biotin receptor (BR) is also present in human lung cancer cells (A549), we explored the therapeutic properties of compound 1 on A549 xenograft tumor models. Method: The selectivity of compound 1 toward A549 cells was studied with fluorescence microscope and IVIS Spectrum Imaging System. The cytotoxicity was measured using MTT assay. In vivo anti-tumor activity was investigated on the nude mice bearing A549 xenografts. Results: In vitro assays proved that compound 1 could selectively accumulate in A549 cells via the BR-mediated internalization. In vivo imaging and distribution experiments showed that compound 1 could selectively accumulate in tumor tissues of tumor-bearing mice. After 16 days of the treatment, the volumes of tumor in PDT group were obviously smaller than that in other groups. Conclusion: This study demonstrates that compound 1 is a promising photosensitizer and has broad application prospects in clinical PDT of lung cancers.

scholarly journals Discovery of new fluorescent thiazole–pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
ZhaoMin Lin ◽  
ZhaoYang Wang ◽  
XueWen Zhou ◽  
Ming Zhang ◽  
DongFang Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Vascular Endothelial Cell ◽  
Chorioallantoic Membrane ◽  
A549 Cells ◽  
Biological Evaluation ◽  
Human Lung Cancer ◽  
Dependent Manner

AbstractA series of fluorescent thiazole–pyrazoline derivatives was synthesized and their structures were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growth of human non-small cell lung cancer (NSCLC) A549 cells in a dose- and time-dependent manner in vitro and inhibit tumor growth in vivo. The structure–activity relationship (SAR) of the compounds was analyzed. Further mechanism research revealed they could induce autophagy and cell cycle arrest while had no influence on cell necrosis. Compound 5e inhibited the activity of mTOR via FKBP12, which could be reversed by 3BDO, an mTOR activator and autophagy inhibitor. Compound 5e inhibited growth, promoted autophagy of A549 cells in vivo. Moreover, compound 5e showed good selectivity with no influence on normal vascular endothelial cell growth and the normal chick embryo chorioallantoic membrane (CAM) capillary formation. Therefore, our research provides potential lead compounds for the development of new anticancer drugs against human lung cancer.

scholarly journals Nanoparticle induced barrier function assessment at liquid–liquid and air–liquid interface in novel human lung epithelia cell lines

2019 ◽  
Vol 8 (6) ◽  
pp. 1016-1027 ◽  
Author(s):  
Lars Leibrock ◽  
Sandra Wagener ◽  
Ajay Vikram Singh ◽  
Peter Laux ◽  
Andreas Luch
Keyword(s):  
Cell Lines ◽  
Barrier Function ◽  
Human Lung ◽  
Animal Experiments ◽  
A549 Cells ◽  
In Vitro Models ◽  
Cell Models ◽  
Zno Nps

Abstract Inhalation is the most relevant entry point for nanoparticles (NPs) into the human body. To date, toxicity testing of nanomaterials in respect to oral, dermal and inhalative application is mainly based on animal experiments. The development of alternative test methods is the subject of current research. In vitro models can help to investigate mechanistic aspects, as e.g. cellular uptake or genotoxicity and might help to reduce in vivo testing. Lung cell lines are proper in vitro tools to assess NP toxicity. In respect to this, various cell models have been developed during the recent years, but often lack in a proper intact barrier function. However, besides other important in vivo criteria which are still missing like e.g. circulation, this is one basic prerequisite to come closer to the in vivo situation in certain mechanistic aspects such as particle translocation which is an important task for risk assessment of nanomaterials. Novel developed in vitro models may help to investigate the translocation of nanomaterials from the lung. We investigated the barrier function of the recently developed human lung cell lines CI-hAELVi and CI-huAEC. The cells were further exposed to CeO2 NPs and ZnO NPs, and their suitability as in vitro models for toxicological investigations was proven. The obtained data were compared with data generated with the A549 cell line. Measurement of transepithelial resistance and immunohistochemical examination of tight junctions confirmed the formation of a functional barrier for both cell lines for submerged and air–liquid cultivation. For particle exposure, hAELVi and huAEC cells showed comparable results to A549 cells without losing the barrier function. CeO2 NP exposure revealed no toxicity for all cell lines. In contrast, ZnO NPs was toxic for all cell lines at a concentration between 10–50 μg ml−1. Due to the comparable results to A549 cells CI-hAELVi and CI-huAEC offer new opportunities to investigate nanoparticle cell interactions more realistic than recent 2D cell models.

Effects of Probiotics in the Management of Infected Chronic Wounds: From Cell Culture to Human Studies

2020 ◽  
Vol 15 (3) ◽  
pp. 193-206
Author(s):  
Brognara Lorenzo ◽  
Salmaso Luca ◽  
Mazzotti Antonio ◽  
Di M. Alberto ◽  
Faldini Cesare ◽  
...  
Keyword(s):  
Chronic Wounds ◽  
Animal Experiments ◽  
Multidrug Resistant ◽  
Preliminary Evidence ◽  
Human Studies ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Keywords Probiotics

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

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