Lung Adenocarcinoma Epithelial Cell Line Research Articles

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels.

The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier.

Printability study by selective laser sintering of bio-based samples obtained by using PBS as polymeric matrix

The emerging request to reduce the environmental impact of plastics encourages scientists to use novel sustainable polymeric materials for many applications fields.The present paper aims to use for the first-time poly (butylene succinate) (PBS), a biodegradable and compostable polymer, for Selective Laser Sintering (SLS) applications. PBS is a flexible semicrystalline aliphatic polyester, which can represent a very good alternative to the traditional thermoplastic polymers obtained by fossil sources.The present work started from a lab-scale production of PBS powders by means of an emulsion solvent evaporation/precipitation method, with the purpose to increase the number of polymeric powders available for SLS. The obtained PBS powders were first characterized by morphological and thermal point of view, and then employed as innovative polymeric material in SLS to realized 3D printed parts with increasing geometrical complexity. To confirm PBS cytocompatibility, cell proliferation and cell viability assays (MTT and Live&Dead) were measured using a lung adenocarcinoma epithelial cell line (H1299). The in vitro cytotoxicity of the 3D printed material was also investigated, showing no harm on cells.

Novel quinazoline-chromene hybrids as anticancer agents: Synthesis, biological activity, molecular docking, dynamics and ADME studies.

In this study, new quinazoline-chromene hybrid compounds were synthesized. The cytotoxic effects on cell viability of the hybrid compounds were tested against A549 human lung adenocarcinoma and BEAS-2B healthy bronchial epithelial cell lines in vitro. In addition, the ability of the active compounds to inhibit cell migration was tested. Molecular docking studies were performed to evaluate the ligand-protein interactions, and molecular dynamics simulations were performed to determine the interactions and stability of ligand-protein complexes. In silico absorption, distribution, metabolism, and excretion (ADME) studies were conducted to estimate the drug-likeness of the compounds. Compounds 4 (IC50 = 51.2 µM) and 5 (IC50 = 44.2 µM) were found to be the most active agents against A549 cells. They are found to be more selective against A549 cells than the reference drug doxorubicin. They also have the ability to significantly inhibit cell migration. They have the best docking scores against epidermal growth factor receptor (EGFR) (-11.300 and -11.226 kcal/mol) and vascular endothelial growth factor receptor 2 (VEGFR2) (-10.987 and -11.247 kcal/mol), respectively. In MD simulations, compounds 4 and 5 have strong hydrogen bond interactions above 80% of simulation times and showed a low ligand root mean square deviation (RMSD) around 2 Å. According to the ADME analysis, compounds 4 and 5 exhibit excellent drug-likeness and pharmacokinetic characteristics.

Invitro Anticancer Activity of Seagrass Cymodocea Serrulata Against Different Cell Lines

Seagrasses have a long history of being used for a variety of remedial purposes, such as the treatment of fever, skindiseases, muscle pains, wounds, and stomach problems. Cancer is a debilitating disease resulting from uncontrolled proliferation.One major treatment strategy for cancer is the application of chemotherapeutic drugs which kill cancer cells. In this study, theanticancer potentials of Cymodocea serrulata seagrass were investigated against the MCF7 cell line (Human breast adenocarcinomacell line) and SHP-77 (human lung adenocarcinoma epithelial cell line). Cytotoxicity of seagrass extract was determined by MTTassay. The results showed that the ethanolic extract of Cymodocea serrulata has moderate anticancer activity, and the IC50 valuewas recorded. The most potent anticancer activity was observed with the ethanolic extract of C. serrulate with IC50 values of 52.5μg/ml and 51.7μg/ml on MCF7 and SHP-77 cells respectively. The ethanolic extract would be studied further to isolate andcharacterize active components for lead optimization studies.

Antiviral effects and tissue exposure of tetrandrine against SARS-CoV-2 infection and COVID-19.

Tetrandrine (TET) has been used to treat silicosis in China for decades. The aim of this study was to facilitate rational repurposing of TET against SARS-CoV-2 infection. In this study, we confirmed that TET exhibited antiviral potency against SARS-CoV-2 in the African green monkey kidney (Vero E6), human hepatocarcinoma (Huh7), and human lung adenocarcinoma epithelial (Calu-3) cell lines. TET functioned during the early-entry stage of SARS-CoV-2 and impeded intracellular trafficking of the virus from early endosomes to endolysosomes. An in vivo study that used adenovirus (AdV) 5-human angiotensin-converting enzyme 2 (hACE2)-transduced mice showed that although TET did not reduce pulmonary viral load, it significantly alleviated pathological damage in SARS-CoV-2-infected murine lungs. The systemic preclinical pharmacokinetics were investigated based on in vivo and in vitro models, and the route-dependent biodistribution of TET was explored. TET had a large volume of distribution, which contributed to its high tissue accumulation. Inhaled administration helped TET target the lung and reduced its exposure to other tissues, which mitigated its off-target toxicity. Based on the available human pharmacokinetic data, it appeared feasible to achieve an unbound TET 90% maximal effective concentration (EC90) in human lungs. This study provides insights into the route-dependent pulmonary biodistribution of TET associated with its efficacy.

Extraction, Separation and Purification of Bioactive Anticancer Components from Peganum harmala against Six Cancer Cell Lines Using Spectroscopic Techniques

Conventional cancer treatments normally involve chemotherapy or a combination of radio- and chemotherapy. However, the adverse effects of synthetic medicines encouraged the exploration of novel therapeutic medications of a bio-friendly nature. In an effort to explore anticancer compounds from natural resources, crude extract of Peganum harmala (seeds) was fractionated on the basis of polarity, and the fractions were further tested for anticancer activity. Brine shrimp lethality assays and potato disc antitumor assays were used to test each fraction for cytotoxic and antitumor potential. The ethyl acetate fraction was found to be most potent, with LC50 and IC50 values of 34.25 µg/mL and 38.58 µg/mL, respectively. Further activity-guided fractionation led to the isolation of the bioactive compound PH-HM-10 which was identified and characterized by Mass Spectroscopy (MS), Infrared Spectroscopy (IR), Proton Nuclear Magnetic Resonance Spectroscopy (1HNMR), Carbon Nuclear Magnetic Resonance Spectroscopy (13CNMR) and Heteronuclear Single Quantum Correlation (HSQC). Anticancer aspects in the isolated compound were determined against six human cancer cell lines with a maximum anticancer effect (IC50 = 36.99 µg/mL) against the tested human myeloid leukemia (HL-60) cell line, followed by the human lung adenocarcinoma epithelial cell line (A549) and the breast cancer cell line (MCF-7) with an IC50 of 63.5 µg/mL and 85.9 µg/mL, respectively). The findings of the current study suggest that the isolated compound (Pegaharmine E) is significantly active against the tested cancer cell lines and can be further investigated to develop future novel anticancer chemotherapeutic agents.

Bioprospecting of new Antarctic seaweed selective antitumor molecules: chemical characterization and in vitro analysis

BackgroundThe Antarctic continent exposes seaweeds to extreme environmental conditions, which may facilitate the production of novel metabolites. Algae represent a highly diverse group of little explored organisms. Thus, marine biomass has emerged as a possible source of new biologically active molecules for the treatment of diseases requiring novel therapeutic options. PurposeThe ultrasonic and Soxhlet extractions were used to evaluate chemical profiles and antitumor activities of Desmarestia anceps, Iridaea cordata, and Pyropia endiviifolia extracts using solvents of different polarity. MethodsChemical characterization of the extracts was performed using gas chromatography. The anticancer activities of the extracts were evaluated by exposing rat glioma (C6), human glioblastoma (U87), and human lung adenocarcinoma epithelial (A549) cell lines to increasing extract concentrations (10–1000 µg mL−1) for 24 and 48 h. In parallel, rat astrocyte and human lung fibroblast (MRC-5) were treated under the same conditions to represent non-transformed cell controls, and permit tumor selectivity evaluations of the extracts. ResultsAn MTT assay was used to measure cell cytotoxicity. Hexane, chloroform, and ethanol extracts reduced glioma and lung cancer cell viability. The hexane and ethanol extracts of P. endiviifolia showed the best antiproliferative effect, decreasing glioma cell viability by 40% at 10 µg mL−1, and the chloroform extract reduced lung adenocarcinoma cell viability by 50% at 46 µg mL−1 after 24 h of treatment. None of the extracts affected the viability of non-transformed cells, as was observed in tumor cells. Fatty acids, fatty alcohols, and phthalate esters were the main compounds identified in the seaweed extracts. ConclusionsAntarctic seaweeds displayed selective antitumor activity against glioma and lung cancer cells, particularly the endemic red alga P. endiviifolia. Therefore, these algae could play an important role as novel prototype molecule source for oncology drug development.

Gas Chromatographic-Mass Spectrometric Analysis, Antibacterial, Antioxidant and Antiproliferative Activities of the Needle Essential Oil of Abies pindrow growing wild in Kashmir, India

The essential oil composition of the leaves of Abies pindrow, growing in Kashmir, India, along with its antioxidant, antibacterial and anticancer activity is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 12 constituents, representing 99.9% of the total oil. The major constituents of the oil were limonene (38.9%), α-pinene (36.5%), β-pinene (6.9%), and α-selinene (4.4%). The essential oil was dominated by the presence of monoterpene hydrocarbons (90.2%), followed by sesquiterpene hydrocarbons (6.761%), oxygenated sesquiterpenes (2.096%) and oxygenated monoterpenes (0.942%). The monoterpene rich essential oil was subjected to antibacterial activity against 4 Gram negative bacteria and 2 Gram positive bacteria at three different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The oil displayed significant and broad spectrum antibacterial activity against different bacteria used. The minimum inhibitory concentration (MIC) of the active essential oil was determined using Agar Dilution Method. Highest antibacterial activity was shown by the oil against E. Coli (25 mm), and the lowest by Bacillus subtilis (14 mm) and Pseudomonas aeruginosa (14 mm). The oil was subjected to cytotoxic activity by MTT assay against human mammary carcinoma (MCF), human ductal breast epithelial tumour (T47D), human lung adeno-carcinoma epithelial (A549) and rat glial (C6) cell lines at three different concentrations. The results revealed significant sensitization of the cell lines with highest inhibition against human ductal breast epithelial cell line (51%) and the lowest against rat glial cell line (33%) at a concentartion of 50 μg/mL. The oil displayed a significant free radical scavenging activity with DPPH.

Analysis of Peganum harmala, Melia azedarach and Morus alba extracts against six lethal human cancer cells and oxidative stress along with chemical characterization through advance Fourier Transform and Nuclear Magnetic Resonance spectroscopic methods towards green chemotherapeutic agents

Traditional medicines implicate consumption of plant crude extracts, which may consist of extensive phytochemical diversity. Overall, the most biologically active extract of Peganum harmala (seeds) exhibited significant cytotoxic activity on Artemia salina with LC50 value of 61.547 µg/mL, while P. harmala (roots) [LC50 = 124.229 µg/mL] and M. azedarach (fruits) [LC50 = 147.813 µg/mL] showed moderate cytotoxic potential. P. harmala (seeds) extract also showed the maximum antitumor potential with 52.278 µg/mL LC50. Branches of P. harmala and Morus alba were not active in both bioassays. These outcomes were further reinforced by the levels of phenolics and flavonoids checked against gallic acid and quercetin equivalents, respectively, by standard curves. Current study aims to isolate, structurally characterize and analyze the bioactive compound from plant extracts by using chromatographic and spectrophotometric techniques. Bioactivity guided isolation of extracts led to the isolation of PH-HM-16 from ethyl acetate fraction P. harmala seeds. Chemical structure of PH-HM-16 was elucidated by ESI-MS, 1H NMR, 13C NMR, HSQC and IR spectrum. The results demonstrated significant positive anticancer activities against six human cancer cell lines assessed through MTT cancer cell growth inhibition assay. PH-HM-16 was most effective against prostate cancer cell lines [IC50 = 17.63 µg/mL] followed by breast cancer cell line MCF7 [IC50 value of 41.81 µg/mL]. IC50 value of PH-HM-16 against human myeloid leukemia cell line HL-60 and human colorectal tumor cells HCT-116 was observed as 68.77 µg/mL and 71.54 µg/mL respectively. The IC 50 value of PH-HM-16 compound was not significant against human gastric cancer SGC-7901 (111.89 µg/mL) and human lung adenocarcinoma epithelial cell line A549 (176.04 µg/mL). Isolated bioactive metabolite PH-HM-16 possesses significant antitumor potential so this could be the first step to develop an effective anticancer agent. Hence, this compound represents a promising potential to be chemically standardized or developed into pharmaceuticals for the chemoprevention and/or the treatment of certain types of cancer, especially as adjuvant phytotherapeutics in conventional chemotherapy.

Platinum(II) Complexes with Bulky Disubstitute Triazolopyrimidines as Promising Materials for Anticancer Agents.

Herein, we present dicarboxylate platinum(II) complexes of the general formula [Pt(mal)(DMSO)(L)] and [Pt(CBDC)(DMSO)(L)], where L is dbtp 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine) or ibmtp (7-isobutyl-5-methyl-1,2,4- triazolo[1,5-a]pyrimidine), as prospective prodrugs. The platinum(II) complexes were synthesized in a one-pot reaction between cis-[PtCl2(DMSO)2], silver malonate or silver cyclobutane-1,1-dicarboxylate and triazolopyrimidines. All platinum(II) compounds were characterized by FT-IR, and 1H, 13C, 15N and 195Pt NMR; and their square planar geometries with one monodentate N(3)-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine, one S-bonded molecule of dimethyl sulfoxide and one O,O-chelating malonato (1, 2) or O,O-chelating cyclobutane-1,1-dicarboxylato (3, 4) was determined. Additionally, [Pt(CBDC)(dbtp)(DMSO)] (3) exhibited (i) substantial in vitro cytotoxicity against the lung adenocarcinoma epithelial cell line (A549) (IC50 = 5.00 µM) and the cisplatin-resistant human ductal breast epithelial tumor cell line (T47D) (IC50 = 6.60 µM); and (ii) definitely exhibited low toxicity against normal murine embryonic fibroblast cells (BALB/3T3).

Effects of Nano-SiO2 combining with cold on cytotoxicity and secretion of inflammatory factors in A549 cells

Objective: To investigate the effects of nano-SiO2 and cold on the cytotoxicity and secretion of inflammatory factors in human lung adenocarcinoma epithelial cell line A549. Methods: A549 was used as experimental subject, a single factor multilevel experiment was designed, A549 cells were exposed to 10, 50, 100, 200 μg/ml nano-SiO2 particles and/or cultured at 31℃, 33℃, 35℃ for 48 h. After that, cell morphology was observed and relative cell survival rate was detected. According to the results of single factor analysis and based on the selection of nano-SiO2 dose and temperature that significantly reduced the relative survival rate of A549 cells, the experiment was designed according to 2×2 factor analysis , they were divided into 4 groups: control group(37℃), Nano-SiO2 exposure group, low temperature exposure group, Nano-SiO2 and low temperature composite group. After exposure for 48 h, the supernatant of cell culture medium was collected for detecting the LDH activity by colorimetric method and the levels of cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) were determined by ELISA. The mRNA levels of cellular IL-6 and IL-8 were detected by qRT-PCR. Results: The activities of A549 cells in 100 μg/ml Nano-SiO2 group and 31℃ low temperature group were decreased significantly. Under the combined conditions, the activity of A549 cells was most inhibited (P＜0.01), and the levels of inflammatory factors IL-6 and IL-8 and mRNA were significantly increased (P＜0.01). Conclusion: 100 μg/ml Nano-SiO2 combined with 31℃ cold exposure can synergistically reduce the activity of A549 cells and increase the expression level of inflammatory factors IL-6 and IL-8 .

Activation of aryl hydrocarbon receptor by benzo[a]pyrene increases interleukin 33 expression and eosinophil infiltration in a mouse model of allergic airway inflammation.

We recently demonstrated that benzo[a]pyrene (BaP), the aryl hydrocarbon receptor (AhR) ligand, directly contributes to aggravation of cutaneous allergy in a mouse model of allergic dermatitis. The present study aimed to determine whether BaP-induced AhR activation results in development of airway inflammation. Initially, the potential for a direct relationship between BaP-induced AhR activation and airway inflammation was investigated in vivo, using a mouse model of type 2 helper T cell (Th2) hapten toluene-2,4-diisocyanate (TDI)-induced airway inflammation. Mice were orally administered BaP at 48, 24, and 4 h before the final allergen challenge. Oral administration of BaP showed a significant increase in lung inflammation and eosinophil infiltration. While expression of Th2 cytokines such as interleukin 4 (IL-4) and IL-13 was not affected by exposure to BaP, AhR activation significantly increased IL-33 expression. To confirm the in vivo results, in vitro experiments were performed using the human eosinophilic leukemia cell line (EOL-1), human bronchial epithelial cell line (BEAS-2B), and human lung adenocarcinoma epithelial cell line (A549). Results indicated that pre-treatment with BaP increased expression of IL-8 in house dust mite-activated EOL-1, BEAS-2B, and A549 cells. In addition, IL-33 levels in BEAS-2B cells were significantly increased after BaP exposure. Our findings indicated that BaP-induced AhR activation is involved in the pro-inflammatory response in respiratory allergy, and that this effect may be mediated by increased IL-33 expression and eosinophil infiltration.

Carvedilol serves as a novel CYP1B1 inhibitor, a systematic drug repurposing approach through structure-based virtual screening and experimental verification

Cytochrome P450 1B1 (CYP1B1) is a promising target for prevention and therapy of cancer, particularly those with drug resistance, stimulating cancer cell survival, and promoting cancer resistance. In view of the extreme complexity and high risk in drug discovery and development, a drug repurposing strategy was applied in the present study to find potential CYP1B1 inhibitors through structure-based virtual screening in the FDA database. Intriguingly, after a thorough assessment of docking scores, binding affinities, as well as binding modes, six compounds were highlighted for further verification. In fact, both carvedilol and indacaterol showed inhibitory activity towards human CYP1B1 with the IC50 of 1.11 μM and 59.52 μM, respectively, according to EROD assay; however, neither docking score nor the detailed binding mode of carvedilol in the hit pose dictated to be a superior CYP1B1 inhibitor to indacaterol, which called for the necessity to re-access the binding mode of carvedilol. Thus, the top two representative docking poses of carvedilol were re-assessed. Indeed, compared to the one hit in the virtual screening (due to a false positive Glide gscore), the other docking pose exhibited ideal performance in both molecular dynamics (MD) simulation, binding free energy, and density functional theory (DFT) calculation evaluations. This identification of the exact binding pose of carvedilol is not only essential for a better understanding of the mechanism underlying its activity, but also contributes to uncovering the structure-activity relationship of CYP1B1 inhibitors. Of note, carvedilol exhibited direct cytotoxicity against both human lung adenocarcinoma epithelial cell line A459 and its Taxol-resistant subline (A549/Taxol). In particular, it showed superior toxicity towards A549/Taxol cells that overexpressed CYP1B1, which further supported its potential to be an effective CYP1B1 inhibitor.

Synthesis and Characterization of a Novel Near-Infrared Fluorescent Probe for Living Cells Imaging.

Currently, optical probes with near-infrared (NIR) fluorescence are of great interest in chemical biology. In the present study, we designed and synthesized a novel NIR fluorescent probe, IR789. IR789 has high selectivity and sensitivity for living cells imaging. The stronger excitation and emission characteristics suggested its dominant optical properties over ICG. IR789 also showed a high affinity and inconspicuous cytotoxicity at the cellular level. The results of fluorescent image in living A549 cells (human lung adenocarcinoma epithelial cell line) further demonstrated its potential applications for biomedical diagnosis in biological systems utilization of nanotechnology.

Novel near-infrared fluorescent probe for live cell imaging.

Near infrared (NIR) fluorescent probes play a crucial role in biological system imaging. A novel NIR fluorescent probe, IR787, was designed in the present study. Compared with indocyanine green (ICG), IR787 showed lower background fluorescent interference and higher fluorescence enhancement. Fluorescence intensities were detected by a Cary Eclipse fluorescence spectrophotometer. The interference of intracellular ions (Cu2+, Ca2+, Mg2+ and Zn2+) on the measurement was negligible, which indicated a good photostability of IR787. MTT assay demonstrated that cell viability of human lung adenocarcinoma epithelial cell line A549 was not significantly affected by the use of the IR787 probe compared with the ICG probe. This result suggested that the IR787 probe was safe for in vitro cell imaging. In vitro NIR optical imaging experiments further revealed cellular uptake and strong intracellular NIR fluorescence of the IR787 probe in A549 cells. The excitation wavelength was 787 nm for IR787. Compared with the previously reported NIR fluorescent probe ICG, the IR787 NIR fluorescent probe had improved prospects for intracellular imaging. IR787 may play a pivotal role in the understanding cell biology, pharmacology and disease diagnosis.

Designing siRNA-conjugated plant oil-based nanoparticles for gene silencing and cancer therapy

In this study, the anticancer activities of two siRNA carriers were compared using a human lung adenocarcinoma epithelial cell line (A549). Firstly, poly(styrene)-graft-poly(linoleic acid) (PS-g-PLina) and poly(styrene)-graft-poly(linoleic acid)-graft-poly(ethylene glycol) (PS-g-PLina-g-PEG) graft copolymers were synthesized by free-radical polymerization. PS-PLina and PS-PLina-PEG nanoparticles (NPs) were prepared by solvent evaporation method and were then characterized. The size was found as 150 ± 10 nm for PS-PLina and 184 ± 6 nm for PS-PLina-PEG NPs. The NPs were functionalized with poly(l-lysine) (PLL) for c-myc siRNA conjugation. siRNA entrapment efficiencies were found in the range of 4–63% for PS-PLina-PLL and 6–42% for PS-PLina-PEG-PLL NPs. The short-term stability test was realised for 1 month. siRNA release profiles were also investigated. In vitro anticancer activity of siRNA-NPs was determined by MTT, flow cytometry, and fluorescence microscopy analyses. Obtained findings showed that both NPs systems were promising as siRNA delivery tool for lung cancer therapy.

In-vitro cytotoxicity of Trigona itama honey against human lung adenocarcinoma epithelial cell line (A549)

IntroductionMany efforts have been made to identify natural alternatives to reduce the side effects of cytotoxic drugs in cancer treatment. With this in mind, the current study aimed to investigate the cytotoxicity effects of one of the multifloral Malaysian honey, Kelulut honey (Trigona itama), as a potential natural anticancer agent in stimulating apoptosis and cell cycle arrest to a human lung adenocarcinoma epithelial cell line (A549). MethodsThe cells were treated with various concentrations of T. itama honey for 24, 48 and 72 h. The cytotoxicity and cell viability were determined using trypan blue exclusion assay (TBEA) and flow cytometric analysis. ResultsThe moisture content in the analysed honey was 14.3 ± 0.8%, which was within the accepted international standard. The pH, electrical conductivity and proline content were 3.17 ± 0.02, 0.47 mS/cm - 0.55 mS/cm and 19.1 mg/kg 20.2 mg/kg respectively. The findings demonstrated a significant dose and time-dependent inhibitory effect of T. itama honey with the maximum cytotoxic effects observed at 72 h with 20% concentration of T. itama honey, indicating 100% growth inhibition. Meanwhile, IC50 of T. itama honey treatment for A549 cells was determined as 0.62% v/v. Moreover, T. itama honey had a promising cytotoxic effect and proven capable of inducing cell cycle arrest at G2/M phase at 72 h of exposure with IC50 concentration. ConclusionThis study provided prefatory evidence on T. itama honey’s significant anticancer activity against human lung cancer cell lines.

Investigation into perturbed nucleoside metabolism and cell cycle for elucidating the cytotoxicity effect of resveratrol on human lung adenocarcinoma epithelial cells.

In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol (RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrations. Cellular nucleoside metabolic profiling was determined by an established liquid chromatography-mass spectrometry method in A549 cells. RSV resulted in significant decreases and imbalances of deoxyribonucleoside triphosphates (dNTPs) pools suppressing subsequent DNA synthesis. Meanwhile, RSV at high concentration caused significant cell cycle arrest at S phase, in which cells required the highest dNTPs supply than other phases for DNA replication. The inhibition of DNA synthesis thus blocked subsequent progression through S phase in A549 cells, which may partly contribute to the cytotoxicity effect of RSV. However, hydroxyurea (HU), an inhibitor of RNR activity, caused similar dNTPs perturbation but no S phase arrest, finally no cytotoxicity effect. Therefore, we believed that the dual effect of high concentration RSV, including S phase arrest and DNA synthesis inhibition, was required for its cytotoxicity effect on A549 cells. In summary, our results provided important clues to the molecular basis for the anticancer effect of RSV on epithelial cells.

Unique Protein Profiles of Extracellular Vesicles as Diagnostic Biomarkers for Early and Advanced Non-Small Cell Lung Cancer.

Extracellular vesicles (EVs) mediate intercellular communication via transferring proteins and other biological molecules and have been recently investigated as biomarkers of disease. Sensitive and specific biomarkers are required for lung cancer diagnosis and prognosis. The present study screens for abnormal EV proteins in non-small cell lung cancer (NSCLC) using a quantitative proteomics strategy involving LC-MS/MS to identify ideal biomarkers for NSCLC diagnosis. EVs are enriched from the sera of early and advanced NSCLC patients and healthy controls and from cell culture supernatants of lung adenocarcinoma and bronchial epithelial cell lines. In the sera and supernatants, 279 and 632 differentially expressed proteins, respectively, are associated with signaling pathways including extracellular membrane-receptor interaction, focal adhesion, and regulation of the actin cytoskeleton. Thirty-two EV proteins are identified at the intersection of differentially expressed proteins between the NSCLC groups and cell lines. Based on bioinformatics analysis, in silico immunohistochemical, and PRM verification, fibronectin is selected for following in vitro studies and validation with an independent cohort. Fibronectin on EVs is estimated to perform well in the diagnosis of NSCLC patients based on AUC, showing great potential for clinical use and demonstrating the efficacy of this method for EV-associated biomarker screening.

Anti-Cancer Activity of Aloe Vera Ethanolic Leaves Extract against In vitro Cancer Cells

In the present study, anticancer and cytotoxicity of Aloe vera ethanolic leaves extract was evaluated as the leaves of A.vera are reported to have great medicinal value with potential therapeutic applications. The anticancer activities of the ethanolic leaves extract of A.vera were investigated using 3-(4, 5-dimethylthiazole-2yl)-2, 5diphenyl tetrazolium bromide assay on three human cancer cell lines HepG2 (liver cancer), HeLa (human cervical carcinoma cell line) and A549 (human lung adenocarcinoma epithelial cell line). In anticancer studies, A.vera ethanolic leaves extract showed potent proliferation inhibitory activity against HepG2, HeLa and A549 cell lines. The results have shown that the A.vera ethanolic leaves extract contain some active ingredients with the potential of being anticancer agents. A.vera ethanolic leaves extract has the potential to fight against cancer cells. Further work should be carried out on the characterization of specific anticancer components of A.vera.