scholarly journals Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells

Gels ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 243
Author(s):  
Shadab Md ◽  
Samaa T. Abdullah ◽  
Nabil A. Alhakamy ◽  
Ahmad Bani-Jaber ◽  
Ammu Kutty Radhakrishnan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Particle Size ◽  
Sustained Release ◽  
Caspase 3 ◽  
A549 Cells ◽  
Size Analysis ◽  
Scanning Calorimetry ◽  
Pulmonary Tissue ◽  
Sustained Release Formulation ◽  
Gastro Retentive

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.

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

Effects of 5,6-Dihydroxy-2,4-Dimethoxy-9,10-Dihydrophenanthrene on G2/M Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells

2016 ◽  
Vol 44 (07) ◽  
pp. 1473-1490 ◽  
Author(s):  
Wipada Duangprompo ◽  
Kalaya Aree ◽  
Arunporn Itharat ◽  
Pintusorn Hansakul
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Caspase 3 ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Apoptotic Cells ◽  
Mrna Levels ◽  
Cycle Arrest

5,6-dihydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene (HMP) is an active compound isolated from the rhizome extracts of Dioscorea membranacea Pierre, a Thai medicinal plant. This study aimed to investigate the growth-inhibitory and apoptosis-inducing effects of HMP in human lung cancer A549 cells. The antiproliferative and cytotoxic effects of HMP were analyzed by a Sulforhodamine B assay. Cell division, cell cycle distribution and membrane asymmetry changes were each performed with different fluorescent dyes and then analyzed by flow cytometry. Real-time PCR and immunoblotting were used to detect cell cycle- and apoptosis-related mRNA levels and proteins, respectively. The nuclear morphology of the cells stained with DAPI and DNA fragmentation were detected by fluorescence microscopy and gel electrophoresis, respectively. The results showed that HMP exerted strong antiproliferative and cytotoxic activities in A549 cells with the highest selectivity index. It halted the cell cycle in [Formula: see text]/M phase via down-regulation of the expression levels of regulatory proteins Cdc25C, Cdk1 and cyclinB1. In addition, HMP induced early apoptotic cells with externalized phosphatidylserine and subsequent apoptotic cells in sub-[Formula: see text] phase. HMP increased caspase-3 activity and levels of the cleaved (active) form of caspase-3 whose actions were supported by the cleavage of its target PARP, nuclear condensation and DNA apoptotic ladder. Moreover, HMP significantly increased the mRNA and protein levels of proapoptotic Bax as well as promoted subsequent caspase-9 activation and BID cleavage, indicating HMP-induced apoptosis via both intrinsic and extrinsic pathways. These data support, for the first time, the potential role of HMP as a cell-cycle arrest and apoptosis-inducing agent for lung cancer treatment.

Overexpression of Smac Promotes Cisplatin-Induced Apoptosis by Activating Caspase-3 and Caspase-9 in Lung Cancer A549 Cells

2013 ◽  
Vol 28 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Sida Qin ◽  
Chengcheng Yang ◽  
Xifang Wang ◽  
Chongwen Xu ◽  
Shuo Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
A549 Cells ◽  
Caspase 9 ◽  
Induced Apoptosis

scholarly journals Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway

2021 ◽  
Author(s):  
Zhenling Ma ◽  
Wenwen Zhang ◽  
Yaru Wu ◽  
Menghao Zhang ◽  
Lei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Caspase 3 ◽  
A549 Cells ◽  
Cyclophilin A ◽  
Mtor Pathway ◽  
Stress Injury ◽  
Peptidyl Prolyl Isomerase ◽  
Isomerase Activity ◽  
Human Lung Carcinoma

The excessive and inappropriate production of reactive oxygen species (ROS) can cause oxidative stress and is implicated in the pathogenesis of lung cancer. Cyclophilin A (CypA), a member of the immunophilin family, is secreted in response to ROS. To determine the role of CypA in oxidative stress injury, we investigated the role that CypA plays in human lung carcinoma (A549) cells. Here, we showed the protective effect of human recombinant CypA (hCypA) on hydrogen peroxide (H2O2)-induced oxidative damage in A549 cells, which play crucial roles in lung cancer. Our results demonstrated that hCypA substantially promoted cell viability, superoxide dismutase (SOD), glutathione (GSH), and GSH peroxidase (GSH-Px) activities, and attenuated ROS and malondialdehyde (MDA) production in H2O2-induced A549 cells. Compared to H2O2-induced A549 cells, Caspase-3 activity in hCypA-treated cells was significantly reduced. Using Western blotting, we showed that hCypA facilitated Bcl-2 expression and inhibited Bax, Caspase-3, Caspase-7, and PARP-1 expression. Furthermore, hCypA activates the PI3K/Akt/mTOR pathway in A549 cells in response to H2O2 stimulation. Additionally, peptidyl-prolyl isomerase activity was required for PI3K/Akt activation by CypA. This study showed that CypA protected A549 cells from H2O2-induced oxidative injury and apoptosis by activating the PI3K/Akt/mTOR pathway. Thus, CypA might be a potential target for lung cancer therapy.

Synthesis of 5-Alkynyltetrandrine Derivatives and Evaluation of their Anticancer Activity on A549 Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1454-1462 ◽  
Author(s):  
Nana Niu ◽  
Tingli Qu ◽  
Jinfang Xu ◽  
Xiaolin Lu ◽  
Graham J. Bodwell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Coupling Reactions ◽  
Apoptotic Pathway ◽  
Future Design ◽  
Cyt C ◽  
Induced Apoptosis

Background: Lung cancer is one of the most prevalent malignancies and thus the development of novel therapeutic agents for managing lung cancer is imperative. Tetrandrine, a bis-benzyltetrahydroisoquinoline alkaloid isolated from Stephania tetrandra S. Moore, has been found to exert cytotoxic effects on cancerous cells. Methods: A series of 5-alkynyltetrandrine derivatives was synthesized via the Sonogashira cross-coupling reactions and evaluated as potential anti-tumor agents. The anti-tumor activities of 12 compounds on lung cancer cells (A549) were evaluated using the MTT method. The population of apoptotic cells was measured using a TUNEL assay. Real-time PCR quantified the gene expression levels of Bcl-2, Bax, survivin and caspase-3. The content of Cyt-C was detected using a Human Cyt-C ELISA kit. Results: Most of these compounds exhibited better activities than tetrandrine itself on A549 cells. Among them, compound 7 showed the highest cytotoxicity among the tested compounds against human lung adenocarcinoma A549 cells with an IC50 of 2.94 µM. Preliminary mechanistic studies indicated that compound 7 induced apoptosis of human lung cancer A549 cells and increased the level of the proapoptotic gene Bax, release of Cyt-C from mitochondria and activation of caspase-3 genes. Conclusion: The results suggest that compound 7 exerts its antitumor activity against A549 cells through the induction of the intrinsic (mitochondrial) apoptotic pathway. These findings will contribute to the future design of more effective anti-tumor agents in lung cancer therapy.

Synthesis and Characterization of Polyimide/Silica Nanocomposites

2011 ◽  
Vol 311-313 ◽  
pp. 96-100
Author(s):  
Jian Li Cheng ◽  
Cun Zhou ◽  
Hao Peng ◽  
Huan Wang ◽  
Yu Sun
Keyword(s):  
Particle Size ◽  
Average Particle Size ◽  
Amic Acid ◽  
Particle Size Analysis ◽  
Size Analysis ◽  
Average Particle ◽  
Scanning Calorimetry ◽  
Silica Nanocomposites ◽  
Transmission Electron ◽  
Size Of Particles

Two kind of polyimide/silica nanocomposites which were recorded poly(amic acid)/ silica(PAA/SiO2) and SiO2in poly(amic acid) ammonium salt(PAS/SiO2) respectively, have been prepared for different methods. The size of SiO2in PAA/SiO2and PAS/SiO2are measured by Particle size analysis and the average particle size are 377nm and 53.7nm. Transmission electron microscopy(TEM) images of PAS/ SiO2confirm that the size of particles are ranged from 40 to 80nm. The stuctures of samples have been characterized by FT-IR spectra. The thermal stability of PAA/SiO2and PAS/SiO2are studied by thermogravimetric analysis (TGA) and the thermal behaviors were investigated by differential scanning calorimetry (DSC) in this paper. It is shown that PAA/SiO2have slightly better thermal properties than that of PAS/SiO2. The results obtained from Instron universal strength tester present the water-solube PAS/SiO2own the excellent mechanical prperties as same as PAA/SiO2.

Synthesis and Characterization Investigations of Laboratory-Synthesized VB-VB2-V3B4 Reinforced Al-7wt.% Si Composites via Mechanical Alloying and Pressureless Sintering

2017 ◽  
Vol 263 ◽  
pp. 189-194
Author(s):  
Sıddıka Mertdinç ◽  
Emre Tekoğlu ◽  
Hasan Gökçe ◽  
Duygu Ağaoğulları ◽  
M. Lütfi Öveçoğlu
Keyword(s):  
Particle Size ◽  
Wear Rate ◽  
Mechanical Alloying ◽  
Weight Ratio ◽  
Sintered Sample ◽  
Optical Microscope ◽  
Particle Size Analysis ◽  
Hydraulic Press ◽  
Size Analysis ◽  
Scanning Calorimetry

In this study, the effect of mechanical alloying (MA) on the microstructural, mechanical and physical properties of vanadium boride particulate reinforced Al-7 wt. % Si matrix composites were investigated. VB-VB2-V3B4 containing vanadium boride hybrid powders were mechanochemically synthesized for 5 h from the V2O5-B2O3-Mg powder blends and leached with hydrochloric acid (HCl) for purification. Laboratory-synthesized VB-VB2-V3B4 powders were incorporated into the Al-7wt. % Si matrix powders with the amount of 2 wt.% via MA for 4h in a SpexTM Mixer/Mill using hardened steel vial/balls with a ball-to-powder weight ratio of 7/1. After the MA process, phase analysis (X-ray diffraction), particle size analysis (laser particle size measurement), surface area analysis (Brunauer-Emmett-Teller measurement) and microstructural characterization (scanning electron microscope (SEM) micrograph) and thermal analysis (differential scanning calorimetry (DSC)) of the non-milled/milled Al-7 wt.% Si-2wt.% (VB-VB2-V3B4) powders were conducted. As-blended and MA’d powders were compacted at a uniaxial hydraulic press to obtain cylindrical compacts with a diameter of 12 mm under a pressure of 400 MPa. Green bodies were sintered at 570°C for 2 h under Ar gas flowing conditions. Microstructural characterizations of the sintered samples were carried out using XRD and optical microscope (OM). Physical and mechanical properties of the composites were investigated in terms of density (Archimedes method), Vickers microhardness and wear rate. The microhardness and wear rate of the 4h of MA’d and sintered sample respectively increased to 0.865±0.256 GPa and 0.0036 mm3/N.m as compared with those of as-blended and sintered sample.

scholarly journals Study on characteristics, properties, and morphology of poly(lactic acid)/chitosan/hydroquinine green nanoparticles

2018 ◽  
Vol 7 (5) ◽  
pp. 417-423
Author(s):  
Nguyen Thi Thu Trang ◽  
Tran Thi Mai ◽  
Nguyen Vu Giang ◽  
Tran Huu Trung ◽  
Do Van Cong ◽  
...  
Keyword(s):  
Particle Size ◽  
Lactic Acid ◽  
Particle Size Analysis ◽  
Poly Lactic Acid ◽  
Size Analysis ◽  
Linear Regression Coefficient ◽  
Scanning Calorimetry ◽  
Calibration Equation ◽  
Basic Particle ◽  
Fast Release

Abstract Poly(lactic acid)/chitosan (PLA/CS) green nanoparticles containing hydroquinine (Hq) were prepared by emulsion method. The content of Hq was 10–50 wt% compared with the weight total of PLA and CS. The characteristics of these nanoparticles were analyzed by Fourier transform infrared (FTIR), differential scanning calorimetry, field emission scanning electron microscopy (FESEM), and particle size analysis. The wavenumbers of C=O, C=N, OH, and CH3 groups in FTIR spectra of the PLA/CS/Hq (PCHq) nanoparticles shifted in comparision with neat PLA, CS, and Hq that proved the interaction between these components. The FESEM images and particle size analysis results showed that the basic particle size of PCHq nanoparticles ranged between 100 and 200 nm. The Hq released from PLA/CS nanoparticles in pH 2 and pH 7.4 solutions was determined by ultraviolet-visible method. The obtained results indicated that the linear regression coefficient of calibration equation of Hq in the above solutions approximates 1. The Hq release from the PCHq nanoparticles includes fast release for the eight first testing hours, and then, controlled slow release. The Hq released process was obeyed according to the Korsmeyer-Peppas kinetic model.

scholarly journals Knockdown of RAD54B expression reduces cell proliferation and induces apoptosis in lung cancer cells

2019 ◽  
Vol 47 (11) ◽  
pp. 5650-5659 ◽  
Author(s):  
Chuan Xu ◽  
Di Liu ◽  
Hong Mei ◽  
Jian Hu ◽  
Meng Luo
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Caspase 3 ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Gene And Protein Expression ◽  
Healthy Lung

Objective RAD54 homolog B (RAD54B), a member of the SNF2/SWI2 superfamily, is implicated in homologous recombination, and high RAD54B expression predicts the prognostic outcomes of lung adenocarcinoma. However, its role in lung carcinogenesis was unclear so this was determined in the present study. Methods We evaluated the gene and protein expression of RAD54B in 15 lung adenocarcinoma tissues and matched adjacent healthy lung tissues by real-time PCR, immunohistochemical staining, and western blotting. A549 lung cancer cells were transduced with lentivirus carrying small hairpin RNA (shRNA) against RAD54B (shRAD54B) or control shRNA (shCtrl), and cell proliferation, viability, apoptosis, and caspase 3/7 activity were evaluated. Results RAD54B protein expression was significantly higher in lung adenocarcinoma tissues than in healthy lung tissues. RAD54B gene expression was high in A549 cells but was efficiently knocked down using shRAD54B with an infection efficiency of 80% and a knockdown ratio of 72.2% compared with shCtrl. Suppressing RAD54B expression in A549 cells significantly reduced cell proliferation and caspase 3/7 activity, and significantly increased the apoptotic rate. Conclusions RAD54B exerts an oncogenic role in lung cancer cell proliferation.

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