scholarly journals Mastoparan, a Peptide Toxin from Wasp Venom Conjugated Fluvastatin Nanocomplex for Suppression of Lung Cancer Cell Growth

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4225
Author(s):  
Nabil A. Alhakamy ◽  
Osama A. A. Ahmed ◽  
Shadab Md ◽  
Usama A. Fahmy
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Particle Size ◽  
Incubation Time ◽  
Late Phase ◽  
A549 Cells ◽  
Sonication Time ◽  
Lung Cancers ◽  
Apoptotic Activity

Lung cancer has a very low survival rate, and non-small cell lung cancer comprises around 85% of all types of lung cancers. Fluvastatin (FLV) has demonstrated the apoptosis and suppression of tumor-cell proliferation against lung cancer cells in vitro. Drug–peptide nanoconjugates were found to enhance the cytotoxicity of anti-cancer drugs. Thus, the present study aimed to develop a nanocomplex of FLV with mastoparan (MAS), which is a peptide that has membranolytic anti-tumor activity. The nanocomplex of FLV and MAS (MAS-FLV-NC) was prepared and optimized for particle size using Box–Behnken design. The amount of FLV had the highest influence on particle size. While higher levels of FLV and incubation time favored higher particle size, a higher level of sonication time reduced the particle size of MAS-FLV-NC. The optimum formula of MAS-FLV-NC used 1.00 mg of FLV and was prepared with an incubation time of 12.1339 min and a sonication time of 6 min. The resultant particle size was 77.648 nm. The in vitro cell line studies of MAS-FLV-NC, FLV, and MAS were carried out in A549 cells. The IC50 values of MAS-FLV-NC, FLV, and MAS were 18.6 ± 0.9, 58.4 ± 2.8, and 34.3 ± 1.6 µg/mL respectively, showing the enhanced cytotoxicity of MAS-FLV-NC. The apoptotic activity showed that MAS-FLV-NC produced a higher percentage of cells in the late phase, showing a higher apoptotic activity than FLV and MAS. Furthermore, cell cycle arrest in S and Pre G1 phases by MAS-FLV-NC was observed in the cell cycle analysis by flow cytometry. The loss of mitochondrial membrane potential after MAS-FLV-NC treatment was significantly higher than those observed for FLV and MAS. The IL-1β, IL-6, and NF-kB expressions were inhibited, whereas TNF-α, caspase-3, and ROS expressions were enhanced by MAS-FLV-NC treatment. Furthermore, the expression levels of Bax, Bcl-2, and p53 strongly established the enhanced cytotoxic effect of MAS-FLV-NC. The results indicated that MAS-FLV-NC has better cytotoxicity than individual effects of MAS and FLV in A549 cells. Further pre-clinical and clinical studies are needed for developing MAS-FLV-NC to a clinically successful therapeutic approach against lung cancer.

scholarly journals Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non-Small-Cell Lung Cancer Cell A549 In Vitro

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Menghuan Guo ◽  
Zhiyuan Liu ◽  
Jing Si ◽  
Jinhua Zhang ◽  
Jin Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
A549 Cells ◽  
Small Cell ◽  
Phase Cell ◽  
G1 Phase ◽  
Small Cell Lung ◽  
Cycle Arrest

Lung cancer remains the leading cause of cancer death worldwide. Late diagnosis, chemoresistance, and metastasis are the main reasons for the high mortality rate of lung cancer. Therefore, the development of other treatments is urgent. Cediranib (CED), a vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, shows promising antitumour activities in various cancers including lung cancer. Here, we explored the effects and the underlying molecular mechanism of CED on non-small-cell lung cancer (NSCLC) cell line A549 cells in vitro. Our results show that CED could inhibit A549 cell proliferation and cloning formation. Meanwhile, G1 phase cell cycle arrest was also found, as featured by the increased proportion of G1 phase cells as well as the reduction of G1 phase relative proteins CDK4/cyclin D1 and CDK2/cyclin E. Moreover, the ratio of LC3-II/LC3-I was elevated significantly in CED-treated groups compared with the controls. Furthermore, the expression of p-Akt, p-P38, p-Erk1/2, and p-mTOR proteins was decreased obviously in the treatment groups. These results suggest that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. Meanwhile, CED may induce autophagy through MAPK/Erk1/2 and Akt/mTOR signal pathway in A549 cells.

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 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.

Formulation, characterisation and In vitro cytotoxic effect of Lens culinarisMedikus seeds extract loaded chitosan microspheres

2021 ◽  
Vol 14 ◽  
Author(s):  
Kripi Vohra ◽  
Meenu Mehta ◽  
Vandana Garg ◽  
Kamal Dua ◽  
Harish Dureja
Keyword(s):  
Lung Cancer ◽  
Particle Size ◽  
Drug Release ◽  
Cytotoxic Effect ◽  
A549 Cells ◽  
Ethanolic Extract ◽  
Entrapment Efficiency ◽  
Reference Drug ◽  
Chitosan Microspheres

Objective: The aim of present study was to formulate chitosan microspheres loaded with ethanolic extract of Lens culinaris Medikus (L.culinaris) seeds (ME) and to explore its anticancer potential against lung cancer (A549) cell line. Methods: Central composite design was applied to prepare and optimise the chitosan microspheres. The prepared microspheres were evaluated for its physicochemical characterisation, in-vitro drug release and anti-cancer potential in-vitro. Results: L.culinaris loaded chitosan microspheres were prepared successfully with suitable particle size, entrapment efficiency and drug release. The developed ME were spherical shaped with the particle size of 2.08 µm. The drug entrapment efficiency and cumulative drug release was found 1.58±0.02% and 81.95±0.35% respectively. Differential Scanning Colorimetry studies revealed no interaction between drugs and polymers used. The cytotoxic effect of the optimised formulation revealed a significant response as compared to the ethanolic extract of L.culinaris seeds (IC50: 22.56 μg/ml vs. 63.58 μg/ml), which was comparable to that of reference drug, doxorubicin (22 µg/ml). These observations demonstrate that the optimised microspheres are effective against lung cancer(A549) cells. Conclusion: The significant cytotoxic response of the developed microspheres may be attributed due to its low particle size, high entrapment efficiency and prolonged drug release profile.

scholarly journals Effect of shRNA-Mediated Knockdown EBF1 Gene Expression on the Proliferation of Lung Cancer Cell Line A549 In Vitro and In Vivo

2021 ◽  
Author(s):  
Lin WANG ◽  
Ding Li ◽  
Li REN ◽  
Honglei FENG
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
A549 Cells ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Cancer Tissues ◽  
Experimental Group

Abstract BackgroundThe incidence of lung cancer is increasing year by year. The study on the proliferation and metastasis of lung adenocarcinoma cells is of positive significance to improve the prognosis of patients with lung adenocarcinoma, but there is still a lack of more effective treatment for the proliferation and metastasis of lung adenocarcinoma cells .Here we find that a lymphocyte lineage specific transcription factor,EBF1, is frequently expressed in human lung cancer tissues and affects the proliferation of tumor cells , Objective to explore the possible mechanism of affecting the proliferation of lung adenocarcinoma cells.MethodsImmunohistochemistry and PCR were used to detect the expression of EBF1 in lung cancer tissues and lung cancer cell lines. According to the interference RNA (shRNA) sequence designed by our laboratory for EBF1 as the target sequence and a random sequence as the negative control, the recombinant retrovirus was constructed and transfected into A549 cells, which were used as A549-shRNA-EBF1 and A549-shRNA-control of experimental group and control group respectively; Knockdown of EBF1 gene was detected by PCR and Western blot. MTT and BrdU staining were used to detect the effect of EBF1-shRNA on the proliferation of A549 cells in vitro;flow cytometry was used to analyze the cell cycle of each group; subcutaneous inoculation of cells in axilla of nude mice was used to observe the effect of EBF1-shRNA on the tumorigenicity of A549 cells in nude mice; Western blot was used to detect the expression of CDK6, P21 and P27 proteins.ResultsEBF1 was not expressed in stromal cells of adjacent tissues and lung cancer tissues, but in nuclei of NSCLC and SCLC cancer cells. EBF1-shRNA knockdown EBF1 gene expression effectively; knockdown EBF1 gene expression can inhibit the proliferation of A549 cells in vitro and in vivo, and block the cell cycle of experimental group at G1 phase; after knockdown EBF1 gene expression, CDK6 protein expression in experimental group cells decreases, while P21 and P27 protein increase.ConclusionsEBF1-shRNA can inhibit the proliferation of lung adenocarcinoma A549 in vitro and in vivo by blocking cell cycle in G1 phase, which involves the decrease of CDK6 expression and the up-regulation of P21 and P27 expression. This study will supplement the theory that heterotopic expression of hematogenous transcription factors in lung cancer affects tumor proliferation and discover new molecular targets for cancer therapy.

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 Antiproliferative Activity and Potential Mechanism of Marine-Sourced Streptoglutarimide H against Lung Cancer Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 79
Author(s):  
Hengju Ge ◽  
Di Zhang ◽  
Muran Shi ◽  
Xiaoyuan Lian ◽  
Zhizhen Zhang
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Lung Cancer Cells ◽  
Potential Mechanism ◽  
Nucleotide Synthesis ◽  
Factor C ◽  
Antiglioma Activity

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.

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

scholarly journals Nuclear-Targeted TAT-PZLL-D3 Co-Delivery DOX and p53 for Chemotherapy Resistance of SCLC

2021 ◽  
Author(s):  
Dan Wang ◽  
Tianshou Cao ◽  
Wanyu Li ◽  
Li Li ◽  
Qunfa Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Tumor Recurrence ◽  
High Efficiency ◽  
Chemotherapy Resistance ◽  
A549 Cells ◽  
Delivery Vector ◽  
Transactivator Of Transcription ◽  
Almost All

Abstract Small cell lung cancer (SCLC) accounts for 13% ~ 15% of lung cancer. It is a subtype with high malignancy and poor prognosis. Almost all patients with SCLC will inevitably have drug resistance and tumor recurrence, which has become an urgent problem in the treatment of SCLC. Nuclear-targeted drug delivery system, which enables intra-nuclear release of anticancer drugs, is expected to address this challenge. In this study, based on transactivator of transcription (TAT)’s active transport property to the nucleus, we developed a high-efficiency nucleus-targeted co-delivery vector that delivers genes and drugs directly into the nucleus of A549 cells. The system is based on a poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) and dendritic polyamidoamine (PAMAM) block copolymer (PZLL-D3) with TAT modified on the surface of carrier. In vitro studies showed that DOX and p53 could can be effectively transported to the nucleus and kill the cancer cells. Thus, such deliver system would bypass the drug resistance and tumor recurrence problem.

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