scholarly journals Poly (1-Vinyl Imidazole) Polyplexes as Novel Therapeutic Gene Carriers for Lung Cancer Therapy

2019 ◽  
Author(s):  
Gayathri kandasamy ◽  
Elena N Danilovtseva ◽  
Vadim annenkov ◽  
Uma maheswari Krishnan
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Vascular Endothelial ◽  
Cytotoxic Effects ◽  
Lung Cancer Therapy ◽  
Si Rna ◽  
Endothelial Growth Factor ◽  
A549 Lung

The present work explores the ability of poly (1-vinyl imidazole) to complex si-RNA against vascular endothelial growth factor (VEGF) and its in vitro efficiency in A549 lung cancer cells. The polyplex formed was found to exhibit 66% complexation efficiency. The complexation was confirmed by gel retardation assay, FTIR and thermal analysis. The blank PVI polymer was not toxic to cells. The polyplex was found to exhibit excellent internalization and escaped the endosome effectively. The polyplex was more effective than the free si-RNA in silencing VEGF in lung cancer cells. The silencing of VEGF was quantified using Western blot which was also reflected in depletion of HIF-1a levels in the cells treated with the polyplex. VEGF silencing by the polyplex was found to augment the cytotoxic effects of the chemotherapeutic agent 5-fluorouracil. Microarray analysis of the mRNA isolated from cells treated with free siRNA and polyplex reveal that the superior VEGF silencing by the polyplex altered the expression levels of several other genes that have been implicated in the proliferation and invasion of lung cancer cells. These results indicate that PVI complexed anti-VEGF can be an effective strategy to counter lung cancer.

scholarly journals Poly(1-vinylimidazole) polyplexes as novel therapeutic gene carriers for lung cancer therapy

2020 ◽  
Vol 11 ◽  
pp. 354-369
Author(s):  
Gayathri Kandasamy ◽  
Elena N Danilovtseva ◽  
Vadim V Annenkov ◽  
Uma Maheswari Krishnan
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Vascular Endothelial ◽  
Cytotoxic Effects ◽  
Lung Cancer Therapy ◽  
Interfering Rna ◽  
Endothelial Growth Factor ◽  
A549 Lung

The present work explores the ability of poly(1-vinylimidazole) (PVI) to complex small interfering RNA (siRNA) silencing vascular endothelial growth factor (VEGF) and the in vitro efficiency of the formed complexes in A549 lung cancer cells. The polyplex formed was found to exhibit 66% complexation efficiency. The complexation was confirmed by gel retardation assays, FTIR and thermal analysis. The blank PVI polymer was not toxic to cells. The polyplex was found to exhibit excellent internalization and escaped the endosome effectively. The polyplex was more effective than free siRNA in silencing VEGF in lung cancer cells. The silencing of VEGF was quantified using Western blot and was also reflected in the depletion of HIF-1α levels in the cells treated with the polyplex. VEGF silencing by the polyplex was found to augment the cytotoxic effects of the chemotherapeutic agent 5-fluorouracil. Microarray analysis of the mRNA isolated from cells treated with free siRNA and the polyplex reveal that the VEGF silencing by the polyplex also altered the expression levels of several other genes that have been connected to the proliferation and invasion of lung cancer cells. These results indicate that the PVI complexes can be an effective agent to counter lung cancer.

scholarly journals Synthesis and preliminary evaluation of the anti-cancer activity on A549 lung cancer cells of a series of unsaturated disulfides

MedChemComm ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 116-119 ◽  
Author(s):  
Fabrizio Olivito ◽  
Nicola Amodio ◽  
Maria Luisa Di Gioia ◽  
Monica Nardi ◽  
Manuela Oliverio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Preliminary Evaluation ◽  
Natural Analogue ◽  
Anti Cancer ◽  
A549 Lung ◽  
Cancer Activity

In this work we synthesized and tested a series of unsaturated disulfides. Two compounds showed a promising anticancer activity in vitro on A549 lung cancer cells compared to the natural analogue.

BMP4 signaling induces senescence and modulates the oncogenic phenotype of A549 lung adenocarcinoma cells

2004 ◽  
Vol 286 (1) ◽  
pp. L81-L86 ◽  
Author(s):  
S. Buckley ◽  
W. Shi ◽  
B. Driscoll ◽  
A. Ferrario ◽  
K. Anderson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Telomerase Activity ◽  
Lung Cancer Cells ◽  
Senescent Phenotype ◽  
A549 Lung

Lung cancer is the most common visceral malignancy in males, with rapidly increasing incidence in females, and a devastatingly poor prognosis. Transforming growth factor (TGF)-β has been shown to induce senescence in A549 lung cancer cells, and both TGF-β and bone morphogenetic protein (BMP) 2 can suppress the transformed phenotype of A549 cells in vitro. We examined the effects of BMP4, another member of the TGF-β superfamily, on specific oncogenic properties of A549 cancer cells. When A549 cancer cells were treated continuously with 100 ng/ml of BMP4, a senescent phenotype was observed after 2 wk of treatment. The BMP-treated cells appeared larger than untreated cells, grew more slowly, had more senescence-associated β-galactosidase activity, and had less telomerase activity, as measured by the telomeric repeat amplification protocol assay. Invasion through Engelbreth Holm-Swarm matrix was inhibited in the senescent cell population. Senescent BMP4-treated cells had lower ERK activation, VEGF expression, and Bcl2 expression than wild-type cells, consistent with a less proliferative, less angiogenic phenotype with increased susceptibility to death by apoptosis. BMP4 treatment also resulted in sustained elevation of Smad1. In vivo xenograft studies in the flanks of nude mice confirmed that the BMP-treated cells were significantly less tumorigenic than untreated cells. Direct overexpression of Smad1 using adenoviral constructs resulted in cell death within 5 days. These studies suggest that BMP4 pathway signaling can induce senescence and thus negatively regulate the growth of A549 lung cancer cells.

scholarly journals Formulation Design, Statistical Optimization, and In Vitro Evaluation of a Naringenin Nanoemulsion to Enhance Apoptotic Activity in A549 Lung Cancer Cells

2020 ◽  
Vol 13 (7) ◽  
pp. 152 ◽  
Author(s):  
Shadab Md ◽  
Nabil A. Alhakamy ◽  
Hibah M. Aldawsari ◽  
Mohammad Husain ◽  
Sabna Kotta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Water Solubility ◽  
Spherical Surface ◽  
Physical Stability ◽  
Lung Cancer Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Burst Release ◽  
A549 Lung

Naringenin (NAR), a flavonoid mainly found in citrus and grapefruits, has proven anti-cancer activities. However, the poor water solubility and low bioavailability of NAR limits its use as a therapeutic agent. The aim of this study was to develop and optimize stable naringenin nanoemulsions (NAR-NE) using a Box–Behnken experimental design to obtain a formulation with a higher efficiency. Anticancer activity of optimized NAR-NE was evaluated in A549 lung cancer cells using cell viability, flow-cytometric assays, and enzyme-linked immunosorbent assay. The stabilized nanoemulsion, which showed a spherical surface morphology, had a globule size of 85.6 ± 2.1 nm, a polydispersity index of 0.263 ± 0.02, a zeta potential of −9.6 ± 1.2 mV, and a drug content of 97.34 ± 1.3%. The NAR release from the nanoemulsion showed an initial burst release followed by a stable and controlled release for a longer period of 24 h. The nanoemulsion exhibited excellent thermodynamic and physical stability against phase separation and storage. The NAR-NE showed concentration-dependent cytotoxicity in A549 lung cancer cells, which was greater than that of free NAR. The percentage of apoptotic cells and cell cycle arrest at the G2/M and pre-G1 phases induced by NAR-NE were significantly higher than those produced by free NAR (p < 0.05). NAR-NEs were more effective than the NAR solution in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. Therefore, stabilized NAR-NE could be a suitable drug delivery system to enhance the effects of NAR in the treatment of lung cancer.

The Inhibitory Mechanism of Compound K on A549 Lung Cancer Cells through EGF Pathway:An in Silico and in Vitro Approach

2016 ◽  
Vol 111 (6) ◽  
pp. 1071 ◽  
Author(s):  
Castro-Aceituno Veronica ◽  
Muhammad Hanif Siddiqi ◽  
Sungeun Ahn ◽  
Natarajan Sathishkumar ◽  
Hae Yong Noh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
In Silico ◽  
Lung Cancer Cells ◽  
Inhibitory Mechanism ◽  
Compound K ◽  
A549 Lung

Vascular endothelial growth factor (VEGF) is a survival factor for neuropilin-1-expressing lung tumour cells

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17084-17084
Author(s):  
M. P. Barr ◽  
G. P. Pidgeon Dr ◽  
K. J. O’Byrne Dr
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Tumour Cell ◽  
Lung Cancer Cells ◽  
Lung Tumour ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Lung Cancer Cell ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

17084 Background: Lung cancer is the leading cause of cancer mortality in Ireland. The formation of new blood vessels, angiogenesis, is essential for tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). Several studies have suggested a role of VEGF as a survival factor for endothelial and some tumour cells. We investigated the effect of VEGF on lung tumour cell survival and examined the VEGF receptor profile of these cells. Methods: A panel of lung cancer cell lines, H460, H647, A549 and SKMES1 were treated with recombinant VEGF (100 ng/ml). Tumour cell survival was assessed using the BrdU proliferation assay. Apoptosis was examined by flow cytometry using Annexin-V and PI staining. VEGF receptor profiles for Flt-1 (VEGFR-1), KDR (VEGFR-2), Neuropilin-1 (NP1) and Neuropilin-2 (NP2) were examined at the mRNA and protein level by RT-PCR and Western blotting, respectively. Tumour cell expression of the Plexin family of signalling receptors was investigated, in addition to the class III Semaphorins which have been shown to bind the Neuropilin receptors. Results: All lung cancer cells expressed NP1 with the exception of the H460 cell line. Using endothelial cells as a positive control, neither VEGFR-1 or VEGFR-2 were identified on the panel of lung cancer cell lines examined at the mRNA and protein level. A dose-response in tumour cell proliferation was observed with the addition of VEGF at 10ng and 100ng/ml. This increase in tumour cell proliferation was significant in all NP1-positive cells, with no effect on NP1-negative H460 cells. VEGF decreased apoptosis in cells expressing NP1, with no effect observed in H460 cells. Our preliminary data show that in addition to NP1, lung cancer cells also express NP2, Plexin-A1, Sema-3A and Sema-3C mRNA which are potential mediators of the NP1 signalling cascade. Conclusions: These results demonstrate that VEGF promotes survival of lung cancer cells, potentially through NP1 signalling. We are currently examining VEGF/VEGFR signalling and the downstream anti- and pro-apoptotic pathways activated in response to VEGF on lung cancer cells. Blockade/inhibition of VEGF and its receptors may offer potential as a therapeutic biological strategy in lung cancer. No significant financial relationships to disclose.

Erlotinib-Loaded Poly(ε-Caprolactone) Nanocapsules Improve In Vitro Cytotoxicity and Anticlonogenic Effects on Human A549 Lung Cancer Cells

2020 ◽  
Vol 21 (6) ◽  
Author(s):  
Franciele Aline Bruinsmann ◽  
Julieti Huch Buss ◽  
Gabriele Dadalt Souto ◽  
Eduarda Schultze ◽  
Aline de Cristo Soares Alves ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
In Vitro Cytotoxicity ◽  
Lung Cancer Cells ◽  
Human A549 ◽  
A549 Lung
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