Chrysin-functionalized gold nanoparticles and paclitaxel exhibit synergistic impact on lung cancer cell lines via regulating the AKT/PPAR-ϒ/ß-Catenin pathway.

Lung cancer has become progressively widespread, posing a challenge to traditional chemotherapeutic drugs such as platinum compounds and paclitaxel owing to growing resistance. Along with that, the chemotherapeutic drugs infer major side effects. The usage of natural compounds as chemosensitizers to boost the efficacy of these chemotherapeutic drugs and minimizing their toxicity is a plausible approach. In our investigation, we employed paclitaxel as the standard chemotherapeutic agent and utilized Chrysin-functionalized gold nanoparticles (CHR-AuNP) to augment its cytotoxicity. Gold nanoparticles were chosen for their inherent cytotoxic properties and ability to enhance Chrysin's bioavailability and solubility.Characterization of CHR-AuNP revealed spherical nanoparticles within the nano-size range (35-70 nm) with a stable negative zeta potential of -22 mV, confirmed by physicochemical analyses including UV-Vis spectroscopy, FT-IR, and visual observation of the wine-red coloration. MTT assay cytotoxicity studies demonstrated CHR-AuNP's superior efficacy compared to CHR alone, with synergistic effects observed in combination with paclitaxel, validated by Compusyn software. Morphological changes indicative of apoptosis were more pronounced with combined treatment, corroborated by AO/ETBr staining and Annexin V assays. Furthermore, the combination treatment amplified ROS production and destabilized mitochondrial membrane potential, while altering the expression of pro-apoptotic and anti-apoptotic proteins. Exploring the mechanistic pathways, we found that the drugs upregulated PPAR-γ expression while suppressing Akt and overexpressing PTEN, thereby impeding the Wnt/ß-catenin pathway commonly dysregulated in lung cancer. This highlights the potential of low-dose combination therapy with paclitaxel and CHR-AuNP as a promising strategy for addressing lung cancer's challenges.

In vitro cancer cell line luminescence-based validation of anticancer phytocompounds obtained from Leucas biflora against HELA cervical and A549 lung cancer cells.

Current research aims to screen the anticancer prospective of Leucas biflora phytocompounds against apoptotic regulator target protein essential for cancer progression. In gas chromatography-mass spectrometry analysis major phytocompounds such as tetracosahexaene, squalene, phytol, 22-stigmasten-3-one, stigmasterol, fluorene, and 1,4-dihydro were identified in ethanolic leaf extract of Leucas biflora. In vitro, the free radical scavenging potential of ethanolic leaf extract of Leucas biflora was examined through its DPPH and ABTS radical scavenging potential IC50 value 15.35 and 13.20 µg/ml, respectively. Dose-dependent cytotoxicity was monitored against both A549 lung cancer and HELA cervical cancer cells. Leucas biflora ethanolic leaf extract highly reduces the cell viability of both HELA and A549 cells in in vitro cytotoxicity assays. Leucas biflora ethanolic extract produces 23.76% and 29.76% viability rates against A549 lung and HELA cervical cancer cell lines, and their IC50 values differ slightly at 95.80 and 90.40 µg/ml, respectively. In molecular docking analysis lung cancer target protein-ligand complex 5Y9T-16132746 showed a maximum score of -14 kcal/mol by exhibiting stable binding affinity and interactions among all screened complexes. Based on docking score nine phytocompounds from Leucas biflora and two reference standard drugs were chosen for further analysis. Further validation reveals that the fluorene, 1,4-dihydro possess good ADMET, Bioactivity and density functional theory indices.

In vitro comparison of viral replication and cytopathology induced by SARS-CoV-2 variants.

A myriad of coronaviruses cause diseases from a common cold to severe lung infections and pneumonia. SARS-CoV-2 was discovered to be the etiologic agent of the Coronavirus pandemic and many laboratory techniques were examined for virus culture and basic and applied research. Understanding the replication kinetics and characterizing the effect the virus has on different cell lines is crucial for developing in vitro studies. With the emergence of multiple variants of SARS-CoV-2, a comparison between their infectivity and replication in common cell lines will help give us a clear understanding of their characteristic differences in pathogenicity. In this study we compared the cytopathic effect and replication of Wild-Type (USA/WA1), Omicron (B.1.1.529), and Delta (B.1.617.2) variants on five different cell lines; VeroE6, VeroE6 cells expressing high endogenous ACE2, VeroE6 cells expressing human ACE2 and TMPRSS2, Calu3 cells highly expressing human ACE2 and A549 cells. This data will aid researchers with experimental planning and viral pathogenicity analysis and provide a baseline for testing any future variants.

Preparation of Biomimetic Selenium-Baicalein Nanoparticles and Their Targeted Therapeutic Application in Nonsmall Cell Lung Cancer.

In this study, we prepared bionic selenium-baicalein nanoparticles (ACM-SSe-BE) for the targeted treatment of nonsmall cell lung cancer. Due to the coating of the A549 membrane, the system has homologous targeting capabilities, allowing for the preparation of target tumor cells. The borate ester bond between selenium nanoparticles (SSe) and baicalein (BE) is pH-sensitive and can break under acidic conditions in the tumor microenvironment to achieve the targeted release of BE at the tumor site. Moreover, SSe further enhances the antitumor effect of BE by increasing the production of ROS in tumor cells. Transmission electron microscopy (TEM) images and dynamic light scattering (DLS) showed that the ACM-SSe-BE had a particle size of approximately 155 ± 2 nm. FTIR verified the successful coupling of SSe and BE. In vitro release experiments indicated that the cumulative release of ACM-SSe-BE at pH 5.5 after 24 h was 69.39 ± 1.07%, which was less than the 20% release at pH 7.4, confirming the pH-sensitive release of BE in ACM-SSe-BE. Cell uptake experiments and in vivo imaging showed that ACM-SSe-BE had good targeting ability. The results of MTT, flow cytometry, Western blot, and cell immunofluorescence staining demonstrated that ACM-SSe-BE promoted A549 cell apoptosis and inhibited cell proliferation. The in vivo antitumor results were consistent with those of the cell experiments. These results clearly suggested that ACM-SSe-BE will be a promising bionic nanosystem for the treatment of nonsmall cell lung cancer.

Untargeted LC/HRMS Metabolomics Analysis and Anticancer Activity Assay on MCF-7 and A549 Cells from Coleus amboinicus Lour Leaf Extract.

Background: Cancer remains the leading cause of death globally, with breast cancer being the foremost cause among women and lung cancer ranking second for both women and men. Objectives: This study aimed to identify the metabolomic content of Coleus amboinicus leaves and evaluate their anticancer activities against breast and lung cancer cells, thereby providing insights into potential alternative treatments for these cancers and initiating research on active isolates from C. amboinicus leaves. Methods: The research methodology involved maceration using ethanol, followed by multistage partitioning with solvents n-hexane, chloroform, and ethyl acetate. Phytochemical screening was performed using standard reagents to detect the presence of alkaloids, phenolics, polyphenols, flavonoids, steroids/triterpenoids, and saponins. Metabolomic profiling was conducted using LC/HRMS, and the anticancer activities against lung cancer cells (A549) and breast cancer cells (MCF-7) were assessed using the MTT assay. Results: The results showed that the C. amboinicus extract contains various secondary metabolite groups such as alkaloids, phenolics and polyphenols, flavonoids, steroids, triterpenoids, and saponins. Conclusions: The diverse metabolomic profile of the C. amboinicus leaf extract demonstrated potential activity against cancer, as evidenced by in vitro tests on lung (A549) and breast (MCF-7) cancer cells. C. amboinicus leaf extract shows promise as an active ingredient in the prevention and alternative natural treatment of lung and breast cancer. Further research and testing, both in vivo and clinically, are warranted.

Targeting BamA, the essential component of the Acinetobacter baumannii ß-barrel assembly machinery, hinders its ability to adhere to and invade human alveolar basal epithelial cell line.

The lungs are commonly targeted by Acinetobacter baumannii. The human alveolar basal epithelial cell line, A549, serves as a valuable in vitro model for probing pathogen-cell dynamics. This study examined two Acinetobacter strains, ATCC 19606 and the clinical isolate 58ST, investigating their adherence, internalization, and cytotoxicity within the A549 cell line to illuminate pathogenic mechanisms. Anti-BamA antibodies were expressed, purified, and detected via indirect ELISA. The toxicity of BamA was assessed across BALB/c mice. Both A. baumannii strains were used to infect A549 cells to scrutinize cell invasion diversity. Serum resistance, biofilm creation and inhibition, adhesion, internalization, and intracellular proliferation of live and inactivated A. baumannii were probed with and without anti-BamA sera. A549 cell viability was evaluated in the presence of live A. baumannii and anti-BamA sera-exposed bacteria. Cytoskeleton inhibitor tests were conducted on epithelial cells. A. baumannii strains displayed differing cell invasion aptitudes, with the clinical variant manifesting the highest invasion capability. During internalization, A. baumannii cells localized within vacuoles and migrated towards the nucleus using a zipper-like invasion mechanism. Bacterial division inside host cells culminated in cell demise. Pre-treatment with anti-BamA antibodies substantially impeded A. baumannii's adherence and invasion in epithelial cells. Microscopic imaging validated the intracellular presence of A. baumannii in A549 cells, verifying their invasive potential and residency. These findings substantiate A. baumannii's capacity to proliferate in epithelial cells, with BamA pivotal role against A. baumannii-epithelial cell interplay. This study augments our insight into A. baumannii pathogenesis, facilitating the development of efficacious strategies against A. baumannii infections.

In vitro cultivation of adherent cells on microscope slides for downstream applications.

In vitro studies with cultured cells are often conducted as an important part of basic research. Adherent cells are typically cultivated in flasks or trays, for which cell staining and subsequent visualization become impractical. We here present a simple step-by-step method for growing adherent cells directly on glass microscope slides, using low-cost equipment readily available in most laboratories. Most parameters such as type of microscope slide (e.g. surface coating), cell seeding concentrations and incubation times can be adjusted according to cell line characteristics and experimental aims, reflecting the methods' flexibility. Through our experiments, microscope slides proved to provide an acceptable surface for cell adhesion and growth of the tested cell lines, as well as being robust and functional with respect to downstream procedures. The method can potentially be combined with different techniques for visualization of experimental effects, such as histological staining methods, fluorescent staining, and immunochemistry. In our method development we have successfully cultivated three different cell lines directly on microscope slides - Atlantic salmon kidney cells (ASK), rainbow trout gill cells (RTgill-W1), and human cancerous lung cells (A549) - and subjected them to various experimental treatments. Finally, as proof-of-concept we provide examples of successful histological staining of the fixed cells. Experimental design in short:•Cultivate cells and calculate cell concentration•Seed a small volume of growth medium with an appropriate number of cells on microscope slide in an area confined by hydrophobic marker•Let cells adhere over night before adding more growth medium or directly conducting experiments and fixing cells for downstream applications.

Forsythiaside A ameliorates bleomycin-induced pulmonary fibrosis by inhibiting oxidative stress and apoptosis.

BACKGROUND: Pulmonary fibrosis (PF) is a common clinically critical disease characterized by high morbidity and high mortality. Forsythiaside A (FA) is a phenylethanol glycoside component in Forsythia suspensa, which has anti-inflammatory, antioxidant, and antiviral activities. However, the effects of FA on bleomycin (BLM)-induced PF are unclear. PURPOSE: The present study explored the role of FA in the amelioration of oxidative stress and apoptosis in BLM-induced PF as well as the possible underlying mechanisms, in vivo and in vitro. METHODS: Network pharmacology was used to collect the effects of FA on BLM-induced PF. Subsequently, further observation of the effects of FA on mice with PF by pulmonary pathological changes, transmission electron microscopy, real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. An in vitro model was constructed by inducing A549 with transforming growth factor beta-1 (TGF-ß1) to observe the effect of FA on epithelial cell apoptosis. RESULTS: Network pharmacology predicted signaling pathways such as IL-17 signaling pathway and Relaxin signaling pathway. The results of in vivo studies showed that FA ameliorated BLM-induced PF through inhibition of fibrosis, modulation of apoptosis, and oxidative stress. In addition, FA promoted TGF-ß1-induced apoptosis in A549 cells. CONCLUSIONS: The results of our study suggested that FA could protect mice against BLM-induced PF by regulating oxidative stress and apoptosis as well as the Epithelial mesenchymal transition pathway.

The anticancer mechanisms of Toxoplasma gondii rhoptry protein 16 on lung adenocarcinoma cells.

Lung adenocarcinoma is the most prevalent subtype of lung cancer, which is the leading cause of cancer-related mortality worldwide. Toxoplasma gondii (T.gondii) Rhoptry protein 16 (ROP16) has been shown to quickly enter the nucleus, and through activate host cell signaling pathways by phosphorylation STAT3 and may affect the survival of tumor cells. This study constructed recombinant lentiviral expression vector of T. gondii ROP16 I/II/III and stably transfected them into A549 cells, and the effects of ROP16 on cell proliferation, cell cycle, apoptosis, invasion, and migration of A549 cells were explored by utilizing CCK-8, flow cytometry, qPCR, Western blotting, TUNEL, Transwell assay, and cell scratch assay, and these effects were confirmed in the primary human lung adenocarcinoma cells from postoperative cancer tissues of patients. The type I and III ROP16 activate STAT3 and inhibited A549 cell proliferation, regulated the expression of p21, CDK6, CyclinD1, and induced cell cycle arrest at the G1 phase. ROP16 also regulated the Bax, Bcl-2, p53, cleaved-Caspase3, and Caspase9, inducing cell apoptosis, and reduced the invasion and migration of A549 cells, while type II ROP16 protein had no such effect. Furthermore, in the regulation of ROP16 on primary lung adenocarcinoma cells, type I and III ROP16 showed the same anticancer potential. These findings confirmed the anti-lung adenocarcinoma effect of type I and III ROP16, offering fresh perspectives on the possible application of ROP16 as a target with adjuvant therapy for lung adenocarcinoma and propelling the field of precision therapy research toward parasite treatment of tumors.

High throughput virtual screening and validation of Plant-Based EGFR L858R kinase inhibitors against Non-Small cell lung Cancer: An integrated approach Utilizing GC-MS, network Pharmacology, Docking, and molecular dynamics.

Lung cancer ranks as the 2nd most common cancer globally. It's the most prevalent cancer in men and the 2nd most common in women. The prominent events in EGFR-mutated non-small-cell lung cancer (NSCLC) include the emergence of the L858R mutation within EGFR exon 21. Despite the promising efficacy of EGFR inhibitors in managing lung cancer, the development of acquired resistance poses a significant hurdle. In the current investigation, we focused on the screening of two phytochemicals, namely Dehydrocostus lactone and Mokkolactone, derived from the Saussurea lappa plant, as potential inhibitors targeting EGFR L858R mutant lung cancer. The chloroform and ethanol extract of the plant demonstrated anti-proliferative activity through the Resazurin chemosensitivity assay, exhibiting an IC50 value of 37.90 ± 0.29 µg/ml with selectivity index 2.4. Through a GC-MS study, we identified 11 phytochemicals for further insilico analysis. These compounds underwent ADMET assessment followed by drug likeliness analysis before being subjected to molecular docking against EGFR L858R, identified through protein-protein interaction network analysis. All phytochemicals exhibited binding energy scores ranging from -6.9 to -8.1 kcal/mol. Dehydrocostus lactone and Mokkolactone were specifically identified for their binding profile. Findings from 100 ns molecular dynamics simulations demonstrated their enhanced stability compared to the reference ligand DJK. This was evident in the root mean square deviation (RMSD) values, ranging from 0.23 ± 0.01 nm to 0.30 ± 0.05 nm, the radius of gyration values, from 1.71 ± 0.01 nm to 1.72 ± 0.01 nm, and the solvent accessible surface area values, from 155.39 ± 2.40 nm2 to 159.32 ± 2.14 nm2. Additionally, favourable characteristics were observed in terms of hydrogen bonding, principal component analysis, and free energy landscape analysis. Examination of their electronic structure via density functional theory revealed efficient properties, with the highest occupied molecular orbital-least unoccupied molecular orbital energy gap values ranging from -3.984 eV to -6.547 eV. Further, in vivo analysis is required to gain a more comprehensive understanding and efficacy of these identified phytochemicals against lung cancer.

Corrigendum: Methotrexate-conjugated zinc oxide nanoparticles exert substantially improved cytotoxic effect on lung cancer cells by inducing apoptosis.

[This corrects the article DOI: 10.3389/fphar.2023.1194578.].

Synthesis of chitosan polyethylene glycol antibody complex for delivery of Imatinib in lung cancer cell lines.

Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second-line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non-small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS-PEG-Ab-Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS-PEG-Ab-Im was 25-30 nm, its surface charge was 13.1 mV, and the shape of CS-PEG-Ab-Im was nearly spherical and cylindrical. The therapeutic potential of CS-PEG-Ab-Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS-PEG-Ab-Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS-PEG-Ab-Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS-PEG-Ab. Besides, cell arresting result exhibits the CS-PEG-Ab-Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS-PEG-Ab-Im can be an ideal nanosystem in NSCLC treatment.

Aerosol exposure at air-liquid-interface (AE-ALI) in vitro toxicity system characterisation: Particle deposition and the importance of air control responses.

Experimental systems allowing aerosol exposure (AE) of cell cultures at the air-liquid-interface (ALI) are increasingly being used to assess the toxicity of inhaled contaminants as they are more biomimetic than standard methods using submerged cultures, however, they require detailed characterisation before use. An AE-ALI system combining aerosol generation with a CULTEX® exposure chamber was characterised with respect to particle deposition and the cellular effects of filtered air (typical control) exposures. The effect of system parameters (electrostatic precipitator voltage, air flowrate to cells and insert size) on deposition efficiency and spatial distribution were investigated using ICP-MS and laser ablation ICP-MS, for an aerosol of CeO2 nanoparticles. Deposition varied with conditions, but appropriate choice of operating parameters produced broadly uniform deposition at suitable levels. The impact of air exposure duration on alveolar cells (A549) and primary small airway epithelial cells (SAECs) was explored with respect to LDH release and expression of selected genes. Results indicated that air exposures could have a significant impact on cells (e.g., cytotoxicity and expression of genes, including CXCL1, HMOX1, and SPP1) at relatively short durations (from 10 mins) and that SAECs were more sensitive. These findings indicate that detailed system characterisation is essential to ensure meaningful results.

Efficient Elimination of mtDNA from Mammalian Cells with 2',3'-Dideoxycytidine.

Mammalian cell lines devoid of mitochondrial DNA (mtDNA) are indispensable in studies aimed at elucidating the contribution of mtDNA to various cellular processes or interactions between nuclear and mitochondrial genomes. However, the repertoire of tools for generating such cells (also known as rho-0 or ρ0 cells) remains limited, and approaches remain time- and labor-intensive, ultimately limiting their availability. Ethidium bromide (EtBr), which is most commonly used to induce mtDNA loss in mammalian cells, is cytostatic and mutagenic as it affects both nuclear and mitochondrial genomes. Therefore, there is growing interest in new tools for generating ρ0 cell lines. Here, we examined the utility of 2',3'-dideoxycytidine (ddC, zalcitabine) alone or in combination with EtBr for generating ρ0 cell lines of mouse and human origin as well as inducing the ρ0 state in mouse/human somatic cell hybrids. We report that ddC is superior to EtBr in both immortalized mouse fibroblasts and human 143B cells. Also, unlike EtBr, ddC exhibits no cytostatic effects at the highest concentration tested (200 µM), making it more suitable for general use. We conclude that ddC is a promising new tool for generating mammalian ρ0 cell lines.

Natural pyrethrins induced developmental toxicity of zebrafish swim bladder in vivo and genotoxicity of lung cells in vitro.

Natural pyrethrins (NPs) are insecticidal compounds isolated and extracted from pyrethrum flowers and are primarily use to control sanitary pests. The lungs become the main target after exposure, and its use may pose potential hazards to respiratory health. Therefore, in this paper, the toxic effects of NPs on human lung cells A549 were investigated and the risk of respiratory toxicity of NPs was studied using zebrafish swim bladder as a model. The results showed that NPs induced cytotoxicity, caused oxidative DNA damage and triggered mitochondria-mediated apoptosis. In addition, exposure to NPs decreased zebrafish embryo survival, hatchability, and heartbeat, and may inhibit normal swim bladder development by disrupting Wnt and Hedgehog signaling pathways. In conclusion, our results suggest that NPs can induce cytotoxicity in A549 in vitro and developmental toxicity in zebrafish in vivo. This study provides a conceptual basis for understanding the mechanisms of toxicity of NPs and assessing respiratory health risks in humans.

Dual Inhibitors of P-gp and Carbonic Anhydrase XII (hCA XII) against Tumor Multidrug Resistance with Piperazine Scaffold.

A new series of piperazine derivatives were synthesized and studied with the aim of obtaining dual inhibitors of P-glycoprotein (P-gp) and carbonic anhydrase XII (hCA XII) to synergistically overcome the P-gp-mediated multidrug resistance (MDR) in cancer cells expressing the two proteins, P-gp and hCA XII. Indeed, these hybrid compounds contain both P-gp and hCA XII binding groups on the two nitrogen atoms of the heterocyclic ring. All compounds showed good inhibitory activity on each protein (P-gp and hCA XII) studied individually, and many of them showed a synergistic effect in the resistant HT29/DOX and A549/DOX cell lines which overexpress both the target proteins. In particular, compound 33 displayed the best activity by enhancing the cytotoxicity and intracellular accumulation of doxorubicin in HT29/DOX and A549/DOX cells, thus resulting as promising P-gp-mediated MDR reverser with a synergistic mechanism. Furthermore, compounds 13, 27 and 32 induced collateral sensitivity (CS) in MDR cells, as they were more cytotoxic in resistant cells than in the sensitive ones; their CS mechanisms were extensively investigated.

Efficacy of GluN2B-Containing NMDA receptor antagonist for antitumor and antidepressant therapy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the predominant subtype of lung cancer. Evidence suggests that the ionotropic glutamate receptor N-methyl-D-aspartate (NMDA) receptor, a critical molecule in the central nervous system, is expressed in NSCLC. However, the specific expression patterns, subcellular localization, functional modulation, and pathological implications of NMDA receptor subtypes in NSCLC have not been fully elucidated. In this study, we employed a multi-disciplinary approach, combining biochemical and molecular biology with electrophysiological recordings and behavioral assays, to investigate these aspects. We reveal the expression of GluN2B-containing NMDA receptors in A549 and H460 NSCLC cell lines and the induction of NMDA receptor-mediated currents by glutamate in A549 cells. Furthermore, the GluN2B-specific inhibitors ifenprodil and Ro 25-6981 significantly reduced cell viability and migration, while promoting apoptosis. Importantly, intraperitoneal administration of ifenprodil in nude mice inhibited the growth of subcutaneous tumors derived from A549 and H460 cells and ameliorated depression-like behaviors. These findings underscore the potential antiproliferative effects of ifenprodil and Ro 25-6981 and suggest that GluN2B-containing NMDA receptors may represent novel therapeutic targets for NSCLC, with the added benefit of potential antidepressant action.

Betacyanins from red pitahaya (Hylocereus polyrhizus) exhibit antiviral response against influenza A virus.

Seasonal influenza affects millions of lives worldwide, with the influenza A virus (IAV) responsible for pandemics and annual epidemics, causing the most severe illnesses resulting in patient hospitalizations or death. With IAV threatening the next global influenza pandemic, it is a race against time to search for antiviral drugs. Betacyanins are unique nitrogen-containing and water-soluble reddish-violet pigments that have been reported to possess antiviral properties against the dengue virus. This study aimed to examine the antiviral effect of betacyanins from red pitahaya (Hylocereus polyrhizus) on IAV-infected lung epithelial A549 cells. HPLC and LC-MS analysis of extracted betacyanin showed four betacyanins in the betacyanin fraction: phyllocactin, hylocerenin, betanin, and isobetanin. Cytotoxicity assay showed that betacyanin fractions were not cytotoxic to A549 cells at concentrations below 100 µg/mL. Betacyanin fraction concentrations of 12.5, 25.0, and 50.0 µg/mL prevented the formation of viral cytopathic effect and reduced virus titer in IAV-infected cells up to 72 h. A downregulation of protein and mRNA nucleoprotein expression levels was observed after treatment with 25.0 and 50.0 µg/mL of betacyanin fraction after 24 h, thereby providing evidence for the antiviral activity of betacyanin from red pitahaya against IAV in vitro.

Identification of 3-((4-Hydroxyphenyl)amino)propanoic Acid Derivatives as Anticancer Candidates with Promising Antioxidant Properties.

Various cancer-associated morbidities remain a growing global health challenge, resulting in a significant burden on healthcare systems worldwide due to high mortality rates and a frequent lack of novel therapeutic options for advanced and localized disease. Reactive oxygen species (ROS) play an important role in cancer pathogenesis and response to chemotherapeutics; therefore, it is crucial to develop novel compounds with both antioxidant and anticancer activity. In this study, a series of previously reported 3-((4-hydroxyphenyl)amino)propanoic acid derivatives (compounds 1-36) were evaluated for their anticancer and antioxidant activities. Compounds 12, 20-22, and 29 were able to reduce A549 cell viability by 50% and suppress A549 cell migration in vitro. These compounds also showed favorable cytotoxicity properties towards noncancerous Vero cells. The most promising candidate, compound 20, exhibited potent antioxidant properties in the DPPH radical scavenging assay. These results demonstrate that 3-((4-hydroxyphenyl)amino)propanoic acid could be further explored as an attractive scaffold for the development of novel anticancer and antioxidant candidates.

Derived from fangchinoline, LYY-35 exhibits an inhibiting effect on human NSCLC cancer A549 cells.

Although fangchinoline has been widely used as an adjunct therapy for a variety of inflammatory and cancerous diseases, its mechanism of action on tumor cells remains unclear. Fangchinoline derivative LYY-35 reduced the number of A549 cells, deformed cell morphology and increased cell debris. Cell viability was significantly reduced, while the same concentration of LYY-35 had little effect on BEAS-2B viability of normal lung epithelial cells. In addition, LYY-35 can also reduce the migration, proliferation and invasion ability of A549 cells. Levels of ß-catenin, ZO-1 and ZEB-1 proteins, biomarkers of cell adhesion and epithelial mesenchymal transformation, were significantly reduced. The levels of superoxide dismutase and lactate dehydrogenase decreased gradually, while the levels of glutathione, malondialdehyde and intracellular and extracellular ROS increased significantly. At the same time, LYY-35 induced increased apoptosis, increased expression of Bax, cleaved caspase3, cleaved PARP1, and decreased expression of Bcl-xl, which blocked the cell cycle to G0/G1 phase. The expressions of cell cycle checkpoint proteins Cyclin B1, Cyclin E1, CDK6, PCNA and PICH were significantly decreased. With the increase of LYY-35 concentration, the trailing phenomenon was more obvious in single cell gel electrophoresis. DNA damage repair proteins: BLM, BRCA-1 and PARP-1 expression decreased gradually.LYY-35 can inhibit the proliferation of non-small cell lung cancer A549 cells, block cell cycle, promote apoptosis, increase ROS production, cause DNA damage and interfere with DNA replication. LYY-35 is promising for the treatment of non-small cell lung cancer in the future.