Inhibitory Effects of Natural Compound Alantolactone on Human Non-small Cell Lung Cancer A549 Cells

Alantolactone is a natural compound identified from the roots of Inula helenium L. that has multiple bio-activities. We examined its inhibitory effects on human non-small cell lung cancer(NSCLC) A549 cells. The an-tiproliferative effect of alantolactone on A549 cells was investigated via MTT[3′-(4,5dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide] assay and its apoptosis-inducing effect was determined by Hoechst staining and flow cytometry. We found that alantolactone significantly inhibited the prol...     

Reactive Oxygen Species (ROS) Activated Liposomal Cell Delivery using a Boronate-Caged Guanidine Lipid

We report boronate-caged guanidine-lipid 1 that activates liposomes for cellular delivery only upon uncaging of this compound by reactive oxygen species (ROS) to produce cationic lipid products. These liposomes are designed to mimic the exceptional cell delivery properties of cell-penetrating peptides (CPPs), while the inclusion of the boronate cage is designed to enhance selectivity such that cell entry will only be activated in the presence of ROS. Boronate uncaging by hydrogen peroxide was verified by mass spectrometry and zeta potential (ZP) measurements. A microplate-based fluorescence assay was developed to study the ROS-mediated vesicle interactions between 1 -liposomes and anionic membranes, which were further elucidated via dynamic light scattering (DLS) analysis. Cellular delivery studies utilizing fluorescence microscopy demonstrated significant enhancements in cellular delivery only when 1 -liposomes were incubated with hydrogen peroxide. Our results showcase that lipid 1 exhibits strong potential as an ROS-responsive liposomal platform for targeted drug delivery applications.     

The Anti-Apoptotic Effects of Caspase Inhibitors in Propyl Gallate-Treated Lung Cancer Cells Are Related to Changes in Reactive Oxygen Species and Glutathione Levels

Propyl gallate [3,4,5-trihydroxybenzoic acid propyl ester; PG] exhibits an anti-growth effect in various cells. In this study, the anti-apoptotic effects of various caspase inhibitors were evaluated in PG-treated Calu-6 and A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Treatment with 800 μM PG inhibited the proliferation and induced the cell death of both Calu-6 and A549 cells at 24 h. Each inhibitor of pan-caspase, caspase-3, caspase-8, and caspase-9 reduced the number of dead and sub-G1 cells in both PG-treated cells at 24 h. PG increased ROS levels, including O₂^∙−, in both lung cancer cell lines at 24 h. Generally, caspase inhibitors appeared to decrease ROS levels in PG-treated lung cancer cells at 24 h and somewhat reduced O₂^∙− levels. PG augmented the number of GSH-depleted Calu-6 and A549 cells at 24 h. Caspase inhibitors did not affect the level of GSH depletion in PG-treated A549 cells but differently and partially altered the depletion level in PG-treated Calu-6 cells. In conclusion, PG exhibits an anti-proliferative effect in Calu-6 and A549 lung cancer cells and induced their cell death. PG-induced lung cancer death was accompanied by increases in ROS levels and GSH depletion. Therefore, the anti-apoptotic effects of caspase inhibitors were, at least in part, related to changes in ROS and GSH levels.     

Target Identification of 22-(4-Pyridinecarbonyl) Jorunnamycin A,a Tetrahydroisoquinoline Derivative from the Sponge Xestospongia sp., in Mediating Non-Small-Cell Lung Cancer Cell Apoptosis

A dysregulation of the cell-death mechanism contributes to poor prognosis in lung cancer. New potent chemotherapeutic agents targeting apoptosis-deregulating molecules have been discovered. In this study, 22-(4-pyridinecarbonyl) jorunnamycin A (22-(4′py)-JA), a synthetic derivative of bistetrahydroisoquinolinequinone from the Thai blue sponge, was semisynthesized by the Steglich esterification method, and its pharmacological mechanism in non-small-cell lung cancer (NSCLC) was elucidated by a network pharmacology approach. All predicted targets of 22-(4′py)-JA and genes related to NSCLC were retrieved from drug-target and gene databases. A total of 78 core targets were identified, and their associations were analyzed by STRING and Cytoscape. Gene ontology and KEGG pathway enrichment analyses revealed that molecules in mitogen-activated protein kinase (MAPK) signaling were potential targets of 22-(4′py)-JA in the induction of NSCLC apoptosis. In silico molecular docking analysis displayed a possible interaction of ERK1/2 and MEK1 with 22-(4′py)-JA. In vitro anticancer activity showed that 22-(4′py)-JA has strong cytotoxic and apoptosis-inducing effects in H460, H292 and A549 NSCLC cells. Furthermore, immunoblotting confirmed that 22-(4′py)-JA induced apoptotic cell death in an ERK/MEK/Bcl-2-dependent manner. The present study demonstrated that 22-(4′py)-JA exhibited a potent anticancer effect that could be further developed for clinical application and showed that network pharmacology approaches are a powerful tool to illustrate the molecular pathways of new drugs or compounds.     

Phosphotungstic Acid Catalyzed One Pot Synthesis of 4,8,8‐Trimethyl‐5‐phenyl‐5,5a,8,9‐tetrahydrobenzo[b] [1,8]Naphthyridin‐6(7H)‐one Derivatives and Their Biological Evaluation Against A549 Lung Cancer Cells

A facile one pot multicomponent synthesis of 1,8‐naphthyridinone derivatives was developed using a mild and reusable phosphotungstic acid catalyst. A 2‐amino picoline, benzaldehyde derivatives and 1,3‐dicarbonyl cyclohexane were used to synthesize 1,8‐naphthyridinones, which was achieved by conventional heating under solvent‐free conditions. All synthesized compounds were characterized by spectral analysis and screened for anticancer activity against A549 lung cancer cells. The results from the cell viability assay showed that the synthesized compounds do have a biological effect at various concentrations on the lung cancer cells. Compounds 4F‐p‐CF₃ and 4H‐VAN showed potential as an antiproliferative agent and a dose‐dependent decline in cell viability was observed.