Edelfosine: An Antitumor Drug Prototype

Background: Lung cancer is the most prevalent cancer and a high fatality disease. Despite of all available therapeutic approaches, drug resistance of chemotherapy agents for patients remain as an obstacle. New drugs integrating immunotherapeutic and conventional cytotoxic effects is a powerful strategy for the treatment of cancer to overcome this limitation. Antineoplastic phospholipids combine both of these activities by affecting lipid metabolism and signaling through lipid rafts. Therefore, they emerge as interesting scaffolds for designing new drugs. Objective: We aimed to evaluate antineoplastic phospholipids as scaffolds for designing new drugs for lung cancer treatment. Methods: The initial screening in A549 cells was performed by MTT assay. Others cytotoxic effects were evaluated in A549 cells by clonogenic assay, Matrigel 3D culture and flow cytometry analyses of cell cycle, apoptosis, mitochondrial membrane electronic potential and superoxide production. Immunological effects of ED were accessed on dendritic cells (DCs) and the expression of some markers were evaluated by flow cytometry. In vivo lung colonization analysis was performed after intravenously injection of A549 cells and daily treatment with ED. Results: Herein, ED showed to be the most efficient compound concerning cytotoxic, thereby, ED was selected for following tests. ED showed a cytotoxic profile in both monolayer and 3D culture and also in vivo models using A549 cells. This profile is due to G0/G1 phase cellular arrest and apoptosis drove by mitochondrial membrane depolarization and superoxide overproduction. Moreover, ED modulated DCs toward an activated pattern by the increased expression of CD83 and a remarkable decreased expression of PD-L1/CD274 on DCs membrane. Conclusions: Thus, ED is an interesting antitumor drug prototype due to not only its direct cellular cytotoxicity but also given its immunological features.

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Mechanism of Hydrogen Gas Promoted Apoptosis of Lung Adenocarcinoma A549 cells through XIAP and BIRC3

10.21203/rs.3.rs-111317/v1 ◽

2020 ◽

Author(s):

Yu Zhang ◽

Gang Chen ◽

Feng Zhen Yan ◽

Fei Li Wang ◽

Chang Dong Wang

Keyword(s):

Lung Cancer ◽

Flow Cytometry ◽

A549 Cells ◽

Hydrogen Gas ◽

Control Group ◽

Logarithmic Phase ◽

Differential Expressed Genes ◽

Lung Adenocarcinoma A549

Abstract Background/AIMLung cancer is the most common reason of cancer-related death in worldwide. Hydrogen gas has been found to have effects on a variety of diseases. At present, it is not reported that the effect of hydrogen gas on lung cancer domestic and overseas. Therefore, we designed this experiment to test the differences in the expression of XIAP, BIRC3 and BAX In vivo and in vitro. Materials and methodsA549 cells in logarithmic phase were treated by 20%, 40%, 60% hydrogen gas respectively. Then the apoptosis of different groups were detected by Flow cytometry. We identify the differential expressed genes(DEGs) by transcriptional. The protein expression of XIAP, BIRC3 and BAX were detected by western blot and immunohistochemistry. ResultThe results demonstrated that hydrogen gas can significantly induce apoptosis compared with the control group. The expression of XIAP and BIRC3 were downregulated in hydrogen group. ConclusionHydrogen gas may promote the apoptosis of lung cancer A549 cells by reducing the expression of XIAP and BIRC3 protein.

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α-Hederin inhibits the growth of lung cancer A549 cells in vitro and in vivo by decreasing SIRT6 dependent glycolysis

Pharmaceutical Biology ◽

10.1080/13880209.2020.1862250 ◽

2020 ◽

Vol 59 (1) ◽

pp. 11-20

Author(s):

Cong Fang ◽

Yahui Liu ◽

Lanying Chen ◽

Yingying Luo ◽

Yaru Cui ◽

...

Keyword(s):

Lung Cancer ◽

A549 Cells

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BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR module

Carcinogenesis ◽

10.1093/carcin/bgaa036 ◽

2020 ◽

Author(s):

Lei Liu ◽

Li Chai ◽

Jingjing Ran ◽

Ying Yang ◽

Li Zhang

Keyword(s):

Lung Cancer ◽

Tumor Suppressor ◽

Colony Formation ◽

Warburg Effect ◽

Poor Prognosis ◽

A549 Cells ◽

Angiogenesis Inhibitor ◽

Metabolic Reprogramming ◽

The Warburg Effect

Abstract Brain-specific angiogenesis inhibitor 1 (BAI1) is an important tumor suppressor in multiple cancers. However, the mechanisms behind its anti-tumor activity, particularly the relationship between BAI1 and metabolic aberrant of a tumor, remained unveiled. This study aimed to investigate whether BAI1 could inhibit biological functions in lung cancer A549 cells and the critical regulating molecules that induce metabolic reprogramming. Immunohistochemistry staining was performed to analyze whether variations in the expression of BAI1 in tumor tissues contributes to poor prognosis of lung cancer. Overexpressed BAI1 (BAI1-OE-A549) and control (Vector-NC-A549) were generated by lentiviral transfection. Biological function assays (proliferation, apoptosis, colony formation, invasion and in vivo metastasis), as well as metabolic reprogramming (by the Warburg effect and the glycolytic rate), were performed in both groups. Our results indicated that lower levels of BAI1 contributed to poor prognosis of lung cancer patients. Furthermore, overexpressed of BAI1 dramatically inhibited proliferation, migration, invasion, colony formation and in vivo metastasis of A549 cells. The Warburg effect and the Seahorse assay revealed that BAI1-OE induced metabolism reprogramming by inhibiting the Warburg effect and glycolysis. Further exploration indicated that BAI1 induced metabolic reprogramming by upregulating stearoyl-CoA desaturase 1 (SCD1) and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Our study revealed a novel mechanism through which BAI1 acted as tumor suppressor by inducing metabolic reprogramming via the SCD1 and HMGCR module.

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Analysis of Erythrocyte Glycophorin-A Variants by Flow Cytometry in Lung Disease Patients Detects the Effect of Tobacco Smoke

Analytical Cellular Pathology ◽

10.1155/2000/512786 ◽

2000 ◽

Vol 21 (1) ◽

pp. 35-40 ◽

Cited By ~ 2

Author(s):

Monica Neri ◽

Elio Geido ◽

Rosangela Filiberti ◽

Roberto Orecchia ◽

Angela Di Vinci ◽

...

Keyword(s):

Lung Cancer ◽

Flow Cytometry ◽

Cancer Risk ◽

Tobacco Smoke ◽

Lung Cancer Risk ◽

Small Population ◽

Cancer Risk Assessment ◽

Lung Cancer Patients ◽

Increased Risk

The glycophoryn A (GPA) assay evaluates somaticin vivomutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment.GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies.We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer.There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p< 0:01). No association was shown with occupational exposure.The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.

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Phytochemical content and potential health applications of pecan [Carya illinoinensis (Wangenh) K. Koch] nutshell

Current Topics in Medicinal Chemistry ◽

10.2174/1568026622666220105104355 ◽

2022 ◽

Vol 22 ◽

Author(s):

Nohemí del C. Reyes-Vázquez ◽

Laura A. de la Rosa ◽

Juan Luis Morales-Landa ◽

Jorge Alberto García-Fajardo ◽

Miguel Ángel García-Cruz

Keyword(s):

Therapeutic Potential ◽

Biological Activities ◽

Heart Diseases ◽

Extraction Methods ◽

New Drugs ◽

Potential Health ◽

In Vivo Models ◽

Phytochemical Content ◽

Pecan Nutshell

Background: The pecan nutshell contains phytochemicals with various biological activities that are potentially useful in the prevention or treatment of diseases such as cancer, diabetes, and metabolic imbalances associated with heart diseases. Objective: To update this topic by means of a literature review and include those that contribute to the knowledge of the chemical composition and biological activities of pecan nutshell, particularly of those related to the therapeutic potential against some chronic degenerative diseases associated with oxidative stress. Method: Exhaustive and detailed review of the existing literature using electronic databases. Conclusion: The pecan nutshell is a promising natural product with pharmaceutical uses in various diseases. However, additional research related to the assessment of efficient extraction methods and characterization, particularly the evaluation of the mechanisms of action in new in vivo models, is necessary to confirm these findings and development of new drugs with therapeutic use.

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Combination of baicalein and docetaxel additively inhibits the growth of non-small cell lung cancer in vivo

Traditional Medicine and Modern Medicine ◽

10.1142/s2575900018500131 ◽

2018 ◽

Vol 01 (03) ◽

pp. 213-218 ◽

Cited By ~ 1

Author(s):

Linwei Lu ◽

Zhengxiao Zhao ◽

Lumei Liu ◽

Weiyi Gong ◽

Jingcheng Dong

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Small Cell Lung ◽

Tumor Bearing ◽

Liver And Kidney ◽

To Receive

Objective: The objective of this study is to preliminarily evaluate the efficacy of the combination of baicalein and docetaxel on non-small cell lung cancer (NSCLC) in vivo. Methods: The subcutaneous model was established by inoculation of A549 cells, and then these tumor-bearing mice were randomly assigned to eight groups to receive normal saline (NS) as control, baicalein alone, Taxotere[Formula: see text] (docetaxel injection) alone or the combination of baicalein and Taxotere[Formula: see text]. The effect of the combination treatment was evaluated by [Formula: see text] value. Tumors were harvested for TUNEL and CD31 immunohistochemical staining and important organs for H&E staining. Results: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg significantly reduced tumor weight and inhibited the growth rate of tumor, displaying the additive effect indicated by the [Formula: see text] value. Increased apoptosis and decreased tumor angiogenesis also provided pathological evidence. Additionally, baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg did not increase toxicity in lung, liver and kidney. Conclusion: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg additively inhibits the growth of NSCLC in vivo, and the mechanism underlying remains to be discovered.

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α-Hederin Inhibits the Growth of Lung Cancer A549 Cells in vitro and in vivo by Increasing SIRT6 Dependent Glycolysis

10.21203/rs.3.rs-36418/v1 ◽

2020 ◽

Author(s):

cong fang ◽

Yahui Liu ◽

Lanying Chen ◽

Yingying Luo ◽

Yaru Cui ◽

...

Keyword(s):

Lung Cancer ◽

Mouse Model ◽

Protein Expression ◽

Glucose Uptake ◽

A549 Cells ◽

Lactate Production ◽

Tumor Xenograft ◽

Xenograft Mouse Model ◽

Atp Generation

Abstract Background: α-hederin an effective component of Pulsatilla chinensis (Bunge) Regel, Studies showed that α-hederin exert many pharmacological activities, However, the effect of α-hederin on metabolism is still unclear. This study aimed to illuminate the role of α-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism of α-hederin. Methods: CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced by α-hederin. Glucose uptake, ATP generation, and reduced lactate production were measured using kits, and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect of α-hederin (5, 10 mg/kg). Glycolytic-related key enzymes hexokinase 2 (HK2), glucose transporters 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter (MCT4), c-Myc, Hypoxia inducible factor-1α (HIF-1α) and Sirtuin 6 (SIRT6) protein expression were detected by western blotting and immunohistochemical staining and SIRT6 inhibitors was verified in A549 cells. Results: Our results showed that cell proliferation was significantly inhibited by α-hederin in a dose-dependent manner and that α-hederin inhibited glucose uptake and ATP generation and reduced lactate production. Furthermore, α-hederin remarkably inhibited HK2, GLUT1, PKM2, LDHA, MCT4, c-Myc, HIF-1α and activated SIRT6 protein expression. Using inhibitors, we proved that α-hederin inhibits glycolysis by activating SIRT6. Moreover, a tumor xenograft mouse model of lung cancer further confirmed that α-hederin inhibits lung cancer growth via inhibiting glycolysis in vivo. Conclusions: α-hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis. The mechanism of glycolysis inhibition includes α-hederin activating the expression of the glycolytic related protein SIRT6.

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In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer

Nature ◽

10.1038/s41586-019-1715-0 ◽

2019 ◽

Vol 575 (7782) ◽

pp. 380-384 ◽

Cited By ~ 38

Author(s):

Milica Momcilovic ◽

Anthony Jones ◽

Sean T. Bailey ◽

Christopher M. Waldmann ◽

Rui Li ◽

...

Keyword(s):

Lung Cancer ◽

Membrane Potential ◽

Small Cell Lung Cancer ◽

Mitochondrial Membrane Potential ◽

Cell Lung Cancer ◽

In Vivo Imaging ◽

Mitochondrial Membrane ◽

Small Cell ◽

Small Cell Lung

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3,5-Dimethyaminophenol is not Mutagenic in Ames Test and HPRT Test and may have Anti-Carcinogenic Potential Against Lung Cancer Cells

Proceedings ◽

10.3390/proceedings2251553 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1553

Author(s):

Ming-Wei Chao ◽

Chia-Yi Tseng ◽

Pei-Ying Lin ◽

Yu-Jung Chang ◽

Özge Köse ◽

...

Keyword(s):

Lung Cancer ◽

Salmonella Typhimurium ◽

Cancer Cells ◽

Cho Cells ◽

Ames Test ◽

A549 Cells ◽

Lung Cancer Cells ◽

Lung Fibroblasts ◽

Carcinogenic Potential

Exposure to 3,5-dimethylaminophenol (3,5-DMAP), the metabolite of the 3-5-dimethylaniline, was shown to cause high levels of oxidative stress in different cells. However, we have shown that this alkylaniline metabolite was non-mutagenic to different strains of Salmonella typhimurium in Ames test and also was found to be not mutagenic to CHO cells in HPRT test. Concerning all the available data, we aimed to observe whether this metabolite may have anti-carcinogenic potential in human non-small cell lung cancer line (A549 cells). 3,5-DMAP caused a dose-dependent increase in cytotoxicity and generation of superoxide (O2-.) and reactive oxygen species (ROS). 3,5-DMAP did not produce significant cytotoxicity to human lung fibroblasts even at very high concentrations; however showed higher cytotoxic effect on A549 lung cancer cells at the same concentrations. 3,5-DMAP also led to molecular events, like increases in apoptotic markers (i.e., p53, Bad, Bax and cytochrome and decreases anti-apoptotic proteins (Bcl-2). Furthermore, 3,5-DMAP provided significant decreases in cell viability of A549 cells and eventually inhibited growth of A549 cells in an in vivo mouse model. Tumor sections showed that 3,5-DMAP down-regulated c-Myc expression but up-regulated p53 and cytochrome c, all of which might result in tumor growth arrest. In conclusion, our findings demonstrate 3,5-DMAP is not mutagenic to Salmonella typhimurium and CHO cells; toxic to A549 cells and therefore may have anti-cancer properties, the importance of which should be elucidated with further mechanistic studies.

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Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Filled with Carboplatin as a Novel Drug Nanocarrier against Murine Lung Cancer Cells

Nanomaterials ◽

10.3390/nano9111572 ◽

2019 ◽

Vol 9 (11) ◽

pp. 1572 ◽

Cited By ~ 3

Author(s):

Daniel Salas-Treviño ◽

Odila Saucedo-Cárdenas ◽

María de Jesús Loera-Arias ◽

Humberto Rodríguez-Rocha ◽

Aracely García-García ◽

...

Keyword(s):

Lung Cancer ◽

Carbon Nanotubes ◽

Tumor Cells ◽

Therapeutic Potential ◽

Cell Uptake ◽

In Vivo Models ◽

Multi Wall Carbon Nanotubes ◽

Lung Cancer Model

Carbon nanotubes (CNTs) have emerged in recent years as a potential option for drug delivery, due to their high functionalization capacity. Biocompatibility and selectivity using tissue-specific biomolecules can optimize the specificity, pharmacokinetics and stability of the drug. In this study, we design, develop and characterize a drug nanovector (oxCNTs-HA-CPT) conjugating oxidated multi-wall carbon nanotubes (oxCNTs) with hyaluronate (HA) and carboplatin (CPT) as a treatment in a lung cancer model in vitro. Subsequently, we exposed TC–1 and NIH/3T3 cell lines to the nanovectors and measured cell uptake, cell viability, and oxidative stress induction. The characterization of oxCNTs-HA-CPT reveals that on their surface, they have HA. On the other hand, oxCNTs-HA-CPT were endocytosed in greater proportion by tumor cells than by fibroblasts, and likewise, the cytotoxic effect was significantly higher in tumor cells. These results show the therapeutic potential that nanovectors possess; however, future studies should be carried out to determine the death pathways involved, as well as their effect on in vivo models.

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