scholarly journals Molecular mechanism of the anti-lung cancer effect of Jin Ning Fang based on network pharmacology and experimental verification

2021 ◽  
Author(s):  
Chunxiao Wu ◽  
Qiquan Yu ◽  
Weizhen Shou ◽  
Kun Zhang ◽  
Yang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Mechanism ◽  
Mrna Level ◽  
A549 Cells ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Apoptosis Pathway ◽  
Protein Protein Interaction ◽  
Anti Cancer

Background: Jin Ning Fang (JNF) is widely used as an adjuvant therapy for lung cancer. However, its molecular mechanism against lung cancer is still unclear. Methods: The chemical compounds JNF were screened from the TCMSP database and its target proteins were then predicted. The genes related to lung cancer were collected from the CTD and DisGeNET databases. Next, targets were integrated with disease-related genes to obtain candidate genes. Functional enrichment and protein-protein interaction (PPI) analysis were also performed, followed by construction of pharmacological network. Meanwhile, Autodock was used to assess the affinity between targets and compound. Finally, the anti-cancer effect of JNF on lung cancer cells was detected and some predicted key genes was validated by using real-time PCR. Results: Twenty-five overlapping targets were obtained, and pathway analysis showed that JNF might exert its anti-cancer function by regulating some biological pathways, such as apoptosis pathway. PPI and pharmacological network revealed several core targets (such as AKT1, AR, and ESR1) and three compounds (quercetin, calcium carbonate, and beta-sitosterol). Then, beta-sitosterol had a high affinity with AKT1, AR, and ESR1. Further in vitro experiments confirmed that JNF could inhibit proliferation and promote apoptosis of A549 cells. The expression of FDPS, PIM1, VCAM1, SLC29A1, NQO1, and ESR1 were significantly decreased, while mRNA level of AR and ANPEP were markedly increased after JNF treatment. Conclusion: JNF may exert anti-lung cancer effect through multiple targets and pathways, and identified genes may be used as potential biomarkers for diagnosis and treatment of lung cancer.

scholarly journals Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 49 ◽  
Author(s):  
Young Yun Jung ◽  
Muthu K. Shanmugam ◽  
Acharan S. Narula ◽  
Chulwon Kim ◽  
Jong Hyun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Mouse Model ◽  
A549 Cells ◽  
Xenograft Model ◽  
Signaling Cascade ◽  
Anticancer Effects ◽  
Anti Cancer

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

scholarly journals Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3930
Author(s):  
Sangun Park ◽  
Tae Kim ◽  
Soo Kim ◽  
Seungkwon You ◽  
Youngmee Jung
Keyword(s):  
Lung Cancer ◽  
Extracellular Matrix ◽  
Three Dimensional ◽  
A549 Cells ◽  
Circulatory System ◽  
Lung Fibroblasts ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.

scholarly journals MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110411
Author(s):  
Cheng-You Jia ◽  
Wei Xiang ◽  
Ji-Bin Liu ◽  
Geng-Xi Jiang ◽  
Feng Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mrna Level ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
G1 Arrest ◽  
Lung Cancer Cell

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.

scholarly journals Bellidifolin Inhibits Proliferation of A549 Cells by Regulating STAT3/COX-2 Expression and Protein Activity

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Li Yan ◽  
Luo Yali ◽  
Li Chenghao ◽  
Feng Caiqin ◽  
Zhu Zhongbo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Network Pharmacology ◽  
Cox 2 ◽  
A549 Lung

Objectives. Bellidifolin (BEL) is one type of tetraoxygenated xanthone that is particularly found in Swertia and Gentiana (Gentianaceae). Despite its broad range of pharmacological activities, it is still unclear whether BEL could be used for lung cancer treatment. Hence, we presently demonstrate the roles of BEL towards the proliferative inhibition of the prototypical A549 lung cancer cells. Materials and Methods. The antiproliferative activity of BEL was initially verified by cellular experiments. A network pharmacology method was then pursued to assess BEL potential molecular targets from the platform for pharmacological analysis of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease enrichment of potential targets and construction of compound-target-disease network maps were performed based on a total of 20 diseases. Two core targets related to the BEL-mediated effect in A549 cells were obtained by importing potential targets into a protein-protein interaction database (STRING) and also analyzing respective data of related targets into this database. Last, these core targets were examined by in vitro analysis and molecular docking. Results. CCK8 assays indicated that treatment with 50–100 μm BEL had an inhibitory effect on the proliferation of human A549 lung cancer cells, whereas this effect was time- and concentration-dependent. As control, treatment with 50–100 μm BEL did not inhibit the proliferation of normal lung epithelial cells (BEAS-2b cell line). H&E staining of BEL-treated A549 cells showed that, upon an increase of drug concentration, nuclear condensation and fragmentation were largely observed. Cell cycle analysis showed that in vitro treatment with 75–100 μm BEL could block A549 cells in S and G2 phases. Western blot analyses showed that after 72 hours of BEL treatment, the level of caspase-8/3 in A549 cells increased, and the level of PARP1 decreased in a dose-dependent manner. Network pharmacology analysis also indicated that lung cancer was the major disease susceptible to BEL treatment. At the same time, STAT3 and COX-2 were identified as two core targets of BEL in lung cancer treatment. Functional analyses further revealed that the cytotoxicity effect of BEL in A549 cells potentially involved the STAT3/COX-2 pathway. Moreover, molecular docking analysis indicated that BEL structure properly matches with COX-2 and STAT3 in space shape, thus illustrating the putative molecular mechanism of BEL’s anticancer effect. Conclusions. Based on a series of in vitro analyses, network pharmacology, and molecular docking, the potential mechanism involving the antiproliferative and cytotoxic effects of BEL in lung cancer cells was investigated. Our study may help providing some theoretical basis for the discovery of novel phytotherapy drugs applicable for the treatment of lung cancer.

scholarly journals In vitro studies of Psorinum 6x on several human cancer cell lines reveal its anti-cancer potential

2021 ◽  
Vol 14 (2) ◽  
pp. 13-14
Author(s):  
Anisur Rahman Khuda-Bukhsh
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Morphological Changes ◽  
A549 Cells ◽  
Cd Spectroscopy ◽  
Anti Cancer

Objective: Psorinum therapy is claimed to combat/ameliorate a variety of human cancers, but for obvious reasons these studies are devoid of any untreated/placebo-treated controls. Therefore, if Psorinum 6x administration to cancer cells of different origin can show visible anti-cancer effects in a controlled in vitro study has been examined. Materials & Methods: Psorinum 6x was provided by Hahnemann Publishing Company (HAPCO), 165 BB Ganguly Street, Kolkata for our research. It was prepared by HAPCO by following standard homoeopathic guidelines from authentic pus cells obtained from an eczema patient being treated at National Institute of Homeopathy, Salt Lake, Kolkata. MTT assay was initially done on several cancer cell lines like A549 (lung cancer), HeLa (cervix cancer), HepG2 (liver cancer) and MCF7 (breast cancer). Psorinum 6x showed strongest anticancer effect against A549 though it also had lesser effect against other cell lines tested. Therefore, A549 was chosen as the model cell line for further study using several relevant protocols. Effects of Psorinum 6x were compared with that of "Placebo 6x" control made of the same stock of "vehicle" used for preparation of Psorinum 6x. Protocols like analysis of cell cycle progression, generation of reactive oxygen species (ROS), change in mitochondrial membrane potential (MMP) and actual cell death (apoptosis), if any, were analysed flow-cytometrically. Whether Psorinum 6x could damage DNA and induce morphological changes were also determined microscopically. Expression of different signal proteins related to cell death (apoptosis) and survival were critically studied by western blot analysis and confocal microscopy. Further, to determine if Psorinum 6x could interact directly with DNA to induce any conformational changes was also determined by circular dichroism (CD) spectroscopy. Results: Psorinum 6x treatment reduced cell viability and inhibited cell proliferation at 24h after treatment, arresting cell cycle at sub-G stage. Upon Psorinum treatment, there were increase of ROS and MMP depolarization, morphological changes and DNA damage typical of apoptosis in A549 cells, along with externalization of phosphatidyl serine. Further, an increase in p53 level, Bax translocation into mitochondria, cytochrome c release into cytosol along with reduction of Bcl2 level and caspase 3 activation were noted which eventually drove A549 cells towards apoptosis; the apoptotic signalling was found to be through mitochondria-mediated caspase 3 dependent pathway. Evidence of direct interaction of Psorinum with cellular DNA was revealed from CD-spectroscopy. Conclusion: Thus, Psorinum 6 x had positive anti-cancer effects against a number of cancer cells, of which it appeared to have strongest effect against the lung cancer cell, A549.

scholarly journals Research on the mechanisms of taraxerol for the treatment of gastric cancer effect based on network pharmacology

2022 ◽  
Vol 36 ◽  
pp. 205873842110639
Author(s):  
Bingjie Huo ◽  
Yanru Song ◽  
Bibo Tan ◽  
Jianbo Li ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanism ◽  
Migration And Invasion ◽  
Network Pharmacology ◽  
Pentacyclic Triterpene ◽  
Pharmacological Analysis ◽  
Anti Cancer ◽  
Cancer Activity

Background: Modern pharmacological studies have shown that traditional Chinese medicine (TCM) Taraxacum mongolicum possesses anti-cancer activity. Taraxerol (TRX) is a pentacyclic triterpene isolated from T. mongolicum, which is widely used in clinical treatment, and its anti-cancer effects have been extensively studied. However, the effects and molecular mechanism of TRX in gastric cancer (GC) have not been fully explicated. Methods: We used public databases to derive information on potential targets of TRX and proteins related to GC. Also, STRING and R3.6.2 software were used to analyze the protein–protein interaction (PPI). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were done to explain the potential mechanism underlying the regulatory role of TRX in GC. The role of TRX in GC was verified by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, apoptosis analysis, Transwell assay, and wound healing assay, and the key signaling pathways were verified. Results: We identified 135 potential targets for the treatment of GC via network pharmacological analysis. GO and KEGG enrichment analysis showed that steroid hormone receptor activity and the PI3K/AKT signaling pathway were the biological processes and pathways with the highest degree of enrichment. Additionally, cellular experiments revealed that TRX inhibited the proliferation, migration, and invasion of GC cells as well as induced G1 phase arrest and apoptosis in GC cells. Conclusion: Here, we used multi-target and multi-pathway network pharmacological analysis to verify the anti-cancer activity of TRX in GC. Also, in vitro experimental data were used to derive the potential molecular mechanism.

scholarly journals The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Hosami ◽  
Azadeh Manayi ◽  
Vahid Salimi ◽  
Farshad Khodakhah ◽  
Mitra Nourbakhsh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Caspase 3 ◽  
Cannabis Sativa ◽  
A549 Cells ◽  
Echinacea Purpurea ◽  
G1 Phase ◽  
Cell Cycle Distribution ◽  
Cb2 Receptor ◽  
Anti Cancer

Abstract Background Considering the advantages of using medicinal herbs as supplementary treatments to sensitize conventional anti-cancer drugs, studying functional mechanisms and regulatory effects of Echinacea purpurea (as a non-cannabinoid plant) and Cannabis sativa (as a cannabinoid plant) are timely and required. The potential effects of such herbs on lung cancer cell growth, apoptosis, cell cycle distribution, cellular reactive oxygen species (ROS) level, caspase activity and their cannabinomimetic properties on the CB2 receptor are addressed in the current study. Methods The cytotoxic effect of both herb extracts on the growth of lung cancer cells (A549) was assessed using the MTT assay. The annexin-V-FITC staining and propidium iodide (PI) staining methods were applied for the detection of apoptosis and cell cycle distribution using flow cytometry. The cellular level of ROS was measured using 7′-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe in flow cytometry. The caspase 3 activity was assessed using a colorimetric assay Kit. Results Echinacea purpurea (EP) root extract induced a considerable decrease in A549 viable cells, showing a time and dose-dependent response. The cell toxicity of EP was accompanied by induction of early apoptosis and cell accumulation at the sub G1 phase of the cell cycle. The elevation of cellular ROS level and caspase 3 activity indicate ROS-induced caspase-dependent apoptosis following the treatment of A549 cells by EP extract. The observed effects of EP extract on A549 growth and death were abrogated following blockage of CB2 using AM630, a specific antagonist of the CB2 receptor. Increasing concentrations of Cannabis sativa (CS) induced A549 cell death in a time-dependent manner, followed by induction of early apoptosis, cell cycle arrest at sub G1 phase, elevation of ROS level, and activation of caspase 3. The CB2 blockage caused attenuation of CS effects on A549 cell death which revealed consistency with the effects of EP extract on A549 cells. Conclusions The pro-apoptotic effects of EP and CS extracts on A549 cells and their possible regulatory role of CB2 activity might be attributed to metabolites of both herbs. These effects deserve receiving more attention as alternative anti-cancer agents. Graphical abstract

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

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

Insight into the molecular mechanism of a herbal injection by integrating network pharmacology and in vitro

2015 ◽  
Vol 173 ◽  
pp. 91-99 ◽  
Author(s):  
Yi-min Ma ◽  
Xin-zhuang Zhang ◽  
Zhen-zhen Su ◽  
Na Li ◽  
Liang Cao ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Network Pharmacology ◽  
Insight Into

Stratification of lung adenocarcinoma patients for d-lemonime intervention based on the expression signature genes

2021 ◽  
Author(s):  
Tengteng Zhu ◽  
Qiang Li ◽  
Limin Xu ◽  
Qi Zhang ◽  
Wenwen Lv ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Essential Oils ◽  
Plant Extract ◽  
Malignant Neoplasm ◽  
Expression Signature ◽  
Signature Genes ◽  
Anti Cancer

Globally, lung cancer ranks as the most lethal malignant neoplasm. D-limonene, a plant extract enriched with essential oils, has been reported to exert anti-cancer effects both in vitro and in...

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