Human Cancer Cell Line A549 Research Articles

Synthesis of (-)-Cannabidiol (CBD), (-)-Δ9- and (-)-Δ8-Tetrahydrocannabinols, Encapsulation of CBD with Nanoparticles for Controlled Delivery and Biological Evaluation.

Cannabidiol (CBD) is garnering increasing interest due to its significant biological activity. This natural compound is one of the major cannabinoids in Cannabis sativa L. In this work, we describe the encapsulation of CBD in solid and hollow pH-sensitive poly(4-vinylpyridine) (solid@p4VP and hollow@p4VP) nanoparticles, and temperature-sensitive poly(N-isopropylacrylamide) (solid@pNIPAM and hollow@pNIPAM) nanoparticles for transport and release CBD in a controlled manner. The CBD loading into these smart polymeric systems was effective and their release profiles, solubility and resistance to stomach and intestinal conditions were evaluated, showing satisfactory properties and improved bioavailability with respect to free CBD. Finally, the A549 human lung cancer cell line was used as lung adenocarcinoma epithelial cellular model to carry out preliminary assays of the in vitro activity of the vehiculized CBD. For all these studies, synthetic CBD was employed, for which a new efficient and scalable synthesis of cannabinoids has been developed.

Unveiling the anticancer potential: Exploring 4-fluoro benzoic acid and piperazine through spectroscopic, X-ray diffraction, DFT and molecular docking analysis

The crystalline substance formed from piperazine and 4-fluorobenzoic acid (PZ-PFBA) was successfully synthesized. This synthesis involved the transfer of protons between the selected acid and base, resulting in the formation of distinct crystalline salt. The SCXRD analysis conforms the salt crystallized in a monoclinic crystal system with a P 21/c space group and lattice parameters are a = 13.0688(14) Å, b = 8.2686(8) Å, and c = 8.2552(9) Å. Hirshfeld surface analysis, a technique for quantifying molecular interactions, was employed to investigate the prepared crystalline salt. Additionally, the salt was subjected to further examination using FT-IR, 1H NMR, 13C NMR, and SCXRD studies. The crystalline salt has major and established biological actions that inhibit the human lung cancer cell line A549. In vitro, and Insilico anticancer tests show that PZ-PFBA has better efficacy against the human cervical cancer cell line (HeLa) and in bioinformatics analysis. PZ-PFBA demonstrated more efficacy in reducing pathogenic strains compared to its parent reactants.

B-251 Comprehensive Proteomics Analysis Reveals an Exosomal Biomarker Signature Useful for Detection of Non-Small Cell Lung Cancer

Abstract Background Lung cancer is the second most commonly diagnosed lung cancer in the world, and Non-Small Cell Lung Cancer is the most prevalent subtype. Tissue biopsy is the gold standard for detecting lung cancer, but is highly invasive as it necessitates the extraction of a sample of tissue for histologic analysis. It also carries risks of bleeding and/or infection, and is inconvenient from a patient perspective. The development of a minimally invasive test, such as one utilizing a blood or urine sample, capable of providing accurate results for lung cancer detection and/or subtyping, would significantly enhance the clinical landscape and streamline patient care. Methods In this study we utilize A549 and H1299 human lung cancer cell lines, differing in cell type, location within the lung, and genetic composition (Kras & p53 status), along with two additional cancer cell lines (HeLa/cervical cancer and SCBO/bladder cancer), as controls. Cell lysate and exosome proteomics data were obtained using data independent acquisition- liquid chromatography mass spectrometry (DIA-LCMS) and analyzed using ProteoDisco 2.0, a custom-designed software application in R. Raw mass spectra data was subject to quantile normalization to mitigate external, non-biological differences between the samples. Differential protein expression was performed and Student's t-test was used to identify significantly different proteins across the sample types. A correlation coefficient matrix and Principal Component Analysis were used to assess global differences, and hierarchical clustering and heat maps allowed for visualizing of specific groups of proteins that separated all sample types. Results Over 1000 proteins were identified in each of the exosome samples, and >7500 proteins were detected in the lysates. Correlation coefficient matrix and PCA demonstrate that exosomal protein profiles, relative to cell lysates, are better at differentiating between the two lung cancer cell lines and controls. Surprisingly, exosomal proteomic patterns are different for the two lung cancers, implicating activation of different signaling pathways. Specifically, hierarchical clustering identified protein clusters showing enrichment for multiple biological processes: H1299 cells manifest enrichment of apical junction proteins and in epithelial-mesenchymal transition (EMT) ontology, while A549 cell lines show enrichment in proteins involved in oxidative phosphorylation. This combination of functional pathways can be used as a biomarker signature to distinguish between these two lung cancer subtypes, and from controls. Conclusions A short list of exosomal proteins, comprising apical junction, EMT, and oxidative phosphorylation constituents can detect lung cancer and further distinguish between subtypes represented by A549 and H1299 lung cancer cells. This biomarker signature has potential for detecting and subtyping lung cancer, to allow for early detection of disease, development of personalized treatment strategies, and result in improved clinical outcomes for this deadly disease.

Chemical Composition, In vitro and In silico Evaluation of Essential Oil from Ocimum tenuiflorum and Coriandrum sativum Linn for Lung Cancer.

Medicinal plants play an essential role in everyday life; plants highly contain therapeutic phytoconstituents commonly used to treat various diseases. This paper discusses the Chemical composition, In vitro antiproliferative activity and In silico study of essential oil extracted from Ocimum tenuiflorum (family Lamiaceae) and Coriandrum sativum (family Apiaceae). In present study GC-MS was used to identify the chemical constituents from O. tenuiflorum and C. sativum. In vitro antiproliferative activity was performed on A549 cancer cell lines. In silico study was performed by Schrodinger's maestro software to identify chemical constituents in both plants as potential EGFR inhibitors for the treatment of lung cancer. The essential oil was extracted by hydro distillation from aerial parts of O. tenuiflorum and C. sativum. The volatile oil sample was analyzed by (GC-MS) Gas Chromatography- Mass Spectrometry. Different chemical constituents were identified based on the retention index and compared with the NIST library. The oil samples from O. tenuiflorum and C. sativum was also evaluated for antiproliferative activity against human lung cancer A549 cell lines. In silico study was performed by Schrodinger maestro software against EGFR (PDB ID 5HG8). O. tenuiflorum essential oil contains Eugenol (42.90%), 2-β-Elemene (25.98%), β- Caryophyllene (19.12%) are the major constituents. On the other side, C. sativum contains nnonadecanol- 1 (16.37%), decanal (12.37%), dodecanal (12.27%), 2-Dodecanal (9.67%), Phytol (8.81%) as the major constituents. Both the oils have shown in vitro antiproliferative activity against human lung cancer cell lines A549 having IC50 values of 38.281 μg/ml (O. tenuiflorum) and 74.536 μg/ml (C. sativum). Molecular interactions of constituents hydro distilled from two oils was analysed by schrodinger maestro software against EGFR (PDB ID 5HG8). The oil sample extracted from O. tenuiflorum showed more antiproliferative activity than C. sativum. In silico study showed that two chemical constituents, namely di-isobutyl phthalate (-7.542 kcal/mol) and dibutyl phthalate (-7.181 kcal/mol) from O. tenuiflorum and one diethyl phthalate (-7.224 kcal/mol) from C. sativum having more docking score than standard Osimertinib which indicates the effectiveness of oils for lung cancer.

Ethyl Oleate, Hexadecenoic Acid, Phytol Profiling of Onosma bracteatum: Antibacterial, Anticancer and Molecular Docking Studies

Research studies on phytochemicals and antibiotics utilizing extracts from medicinal plants have proliferated in the past few years. The phytochemicals profiling, antioxidant capacity, antibacterial properties, antiproliferative potential and molecular docking studies of ethanolic extract of Onosma bracteatum was examined in this study. The extract prepared into ethanol (80%) and identify the presence of phytochemical compounds using GC-MS profiling. The antibacterial potential was investigated in relation to Staphylococcus aureus and Escherichia coli. Further to evaluate the anticancer potential of ethanolic extract of O. bracteatum, the antiproliferative assay (MTT cytotoxicity assay) was performed against Ln-18 (human malignant glioma cell line) and A-549 (Human lung cancer cell line) cells. Ethyl oleate, hexadecenoic acid and phytol were highest in GC-MS and docked against DNA gyrase B (E. coli), β-lactamase (S. aureus) and BCL-2 (apoptosis inhibitor). In antioxidant assay, 78% maximum inhibition of free radical scavenging activity was observed. The zone of inhibition was in the ranges from 9 mm (E. coli) to 20 mm (S. aureus). Furthermore, the ethanolic extract of O. bracteatum demonstrated antiproliferative activity against the cancer cell lines LN-18 and A-549 with growth inhibitions of 84% and 81%. The ethyl oleate was found to be best compound with -8.4 (kcal/mol) binding score in the molecular docking studies. The results showed that O. bracteatum is a good source of phytochemicals and antibacterial compounds with promising anticancerous potential.

Cytotoxic and antibacterial compounds from Schinus terebinthifolia Raddi fruits

Chromatographic procedures of extracts of Schinus terebinthifolia Raddi fruits afforded (Z)-masticadienoic (1) and 3β-masticadienolic (2) acids, tetrahydroamentoflavone (3), and 4-O-methyl gallic acid (4). Addicionally, the derivative 6-oxo masticadienoic acid (1a) was prepared by an allylic oxidation. The chemical structures of obtained compounds were elucidated by spectrometric data analyses. Furthermore, both the semi-synthetic derivative and the metabolites were subjected to in vitro cytotoxicity against the A549 human lung cancer cell line, as well as antimicrobial activity tests. Compounds 2 and 1a exhibited cytotoxicity towards A549 cells with IC50 values of 20.13 and 6.11 µM, respectively. In the tests against pathogens, the CHCl3 and EtOAc soluble fractions of MeOH extract along with the pure compounds, exhibited antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Except for 4-O-methyl gallic acid, the other pure compounds showed inhibitory microbial activities with MIC values ranging from 0.25 μg/mL to 25 μg/mL doses.

Synthesis, Characterization, and Biological Evaluation of Novel [M(η6-arene)2]+ (M = Re, 99mTc) Hosted Terpyridines and Copper Complexes Thereof.

We report the synthesis, characterization, and in vitro biological activities of [Re(η6-arene)2]+-terpyridine conjugates and their CuII complexes. The terpyridine (terpy) chelators were attached to the [Re(η6-arene)2]+ scaffold via secondary amine linkers allowing for heteroleptic mono- and homoleptic bis-terpyridine-substituted chelators. Complexation with CuCl2 afforded the respective square pyramidal [Cu(terpy)Cl2] complexes hosted on the [Re(η6-arene)2]+ scaffold. The chelator conjugates and their respective complexes were found to be remarkably cytotoxic against malignant HT29 and A549 human cancer cell lines in vitro with IC50 values in the low micromolar range. Mitochondrial respiration disruption was identified as a possible mode of action of these novel drug candidates. Crucially, the [Re(η6-arene)2]+ hosts delivered water solubility of the otherwise insoluble [Cu(terpy)Cl2] motif. Importantly, the homoleptic [99mTc(η6-arene)2]+-terpyridine conjugate is available in a single step, which enables the presented system to be used as a theranostic approach to modern medicinal inorganic chemistry.

Unveiling the anticancer potential of novel spirooxindole-tethered pyrazolopyridine derivatives

In the current medical era, human health is confronted with various challenges, with cancer being a prominent concern. Therefore, enhancing the therapeutic arsenal for cancer with a constant influx of novel molecules that selectively target tumor cells while displaying minimal toxicity toward normal cells is imperative. This study delves into the antiproliferative and EGFR kinase inhibitory activities of newly reported spirooxindole-pyrazolo[3,4-b]pyridine derivatives 8a-h and 10a-h. The inhibitory effects on the growth of human cancer cell lines A-549 (lung carcinoma), Panc-1 (pancreatic carcinoma), and A-431 (skin epidermoid carcinoma) were evaluated, and the SAR has been clarified through analysis. With IC50 values in the single-digit micromolar range, compounds 8b, 8d, 10a-b, and 10d were shown to be the most effective antiproliferative candidates against the studied cancer cell lines. They also exerted negligible cytotoxicity (with selectivity scores between 8.63 and 30.02) against the human lung MRC5 cell line. Additionally, we investigated the potential inhibitory action of compounds 8b, 8d, 10a-b, and 10d on EGFR and VEGFR-2. 10a was this investigation’s most effective EGFR inhibitor, with an IC50 value of 0.54 μM. Ultimately, the molecular docking analysis of congener 10a highlighted its effective suppression of EGFR by examining its binding mode and docking score compared to Erlotinib. These findings underscore the potential of spirooxindole-pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents targeting EGFR kinase.

Lupeol-3-carbamate Derivatives: Synthesis and Biological Evaluation as Potential Antitumor Agents.

In the following study, a series of new lupeol-3-carbamate derivatives were synthesized, and the structures of all the newly derived compounds were characterized. The new compounds were screened to determine their anti-proliferative activity against human lung cancer cell line A549, human liver cancer cell line HepG2, and human breast cancer cell line MCF-7. Most of the compounds were found to show better anti-proliferative activity in vitro than lupeol. Among them, obvious anti-proliferation activity (IC50 = 5.39~9.43 μM) was exhibited by compound 3i against all three tumor cell lines. In addition, a salt reaction was performed on compound 3k (IC50 = 13.98 μM) and it was observed that the anti-proliferative activity and water solubility of compound 3k·CH3I (IC50 = 3.13 μM), were significantly enhanced subsequent to the salt formation process. The preliminary mechanistic studies demonstrated that apoptosis in HepG2 cells was induced by compound 3k·CH3I through the inhibition of the PI3K/AKT/mTOR pathway. In conclusion, a series of new lupeol-3-carbamate derivatives were synthesized via the structural modification of the C-3 site of lupeol, thus laying a theoretical foundation for the design of this new anticancer drug.

An efficient green synthesis and in vitro evaluation of novel adamantane-containing 4-thiazolidinone derivatives as anticancer agents

The novel 4-thiazolidinone derivatives incorporating an adamantane moiety were synthesized in high yields through the reaction of N-adamantyl-substituted thioureas and dimethyl acetylenedicarboxylate (DMAD) using an environmentally benign method. These catalyst-free reactions were performed in an ethanol-water mixture at room temperature, with short reaction times of 3–8 minutes. The in vitro anticancer activity of the target compounds was evaluated against the A-549 human non-small cell lung cancer (NSCLC) cell line. Among the target compounds, 2b, 2c, and 2a exhibited promising cytotoxic effects, with IC50 values of 19.07, 32.92, and 63.38 µM, respectively. Additionally, the mechanisms for inhibition of cell growth and induction of apoptotic cell death were assessed using DAPI and Annexin V-FITC staining. The results indicated that the 4-thiazolidinone derivatives incorporating an adamantane moiety have significant potential for the development of anticancer therapeutics.

A new isoprenyl-phenol-type meroterpenoid from mangrove endophytic fungus Aspergillus sp. GXNU-Y65

Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 μM, respectively.

Chemical Composition and Antibacterial, Antioxidant, and Cytotoxic Activities of Essential Oils from Leaves and Stems of Aeschynomene indica L.

The objective of this study was to analyze the chemical composition and evaluate the biological capabilities of the essential oils (EOs) extracted from leaves and stems of wild Aeschynomene indica L. plants by the hydrodistillation method. By using GC-FID/MS, fifty-six and fifty-five compounds, representing 95.1 and 97.6% of the essential oils in the leaves and stems, respectively, were characterized. The predominant constituents of A. indica EOs were (E)-caryophyllene, linalool, viridiflorol, phytol, hexadecanoic acid, trans-verbenol, and α-guaiene. The antibacterial and synergistic activities of the EOs were assessed by microdilution and checkerboard assays. The results revealed a potent inhibition and bactericidal activity against Staphylococcus aureus and Bacillus subtilis with MICs of 0.312-0.625 mg/mL. When combined with traditional antibiotics, the essential oils of A. indica possessed excellent synergistic effects against all tested bacteria. Additionally, the EOs of A. indica leaves showed higher antioxidant activity (IC50 = 0.11 ± 0.01 µg/mL) compared to the stem oil (IC50 = 0.19 ± 0.01 µg/mL) using the ABTS radical scavenging assay. The in vitro cytotoxicity of EOs against human cancer cell lines HepG2, MCF-7, A-549, and HCT-116 was examined, and MTT assays showed that the EOs possessed a significant cytotoxic potential against MCF-7 breast cancer cells, with IC50 values of 10.04 ± 1.82 and 15.89 ± 1.66 μg/mL, and a moderate cytotoxic activity against other tested cells. In conclusion, the A. indica EOs could be considered a potential source of pharmacologically active compounds.

Exploration of Anticancer Activity of Portieria Hornemanni Against Lung Cancer Cellline (A549)

Cancer remains a major global health issue for which there are now no entirely viable treatments. As a result, natural product-based alternative therapies have been suggested. Studies have demonstrated the biological activity of seaweed, particularly its anticancer properties. The review’s main subject is lung cancer. It also lists some substances that have been taken out of a variety of seaweeds and demonstrated to either completely prevent cancer or significantly delay its spread. The main objectives of the study are to find the cytotoxicity effect of Porteria hornimanni in human lung cancer cell line A549 adopting MTT assay and utilizing fluorescent labelling techniques to detect morphological changes in the cells following P. hornimanni therapy.The present study indicates that P. hornemanni’s ethanolic extract exhibits anti-cancer properties in the lung cancer cell line A549.This study shows how cancer cells can employ their anticancer properties. Additional research is necessary to identify the specific chemical in P. hornemanni that has cytotoxic effects on cancer.

Dioxepine-derived surface-capping gold nanoparticles (Dd-AuNPs) induces ROS-mediated apoptosis and cell cycle arrest in A549 human lung cancer cell line

Dioxepine-derived surface-capping gold nanoparticles (Dd-AuNPs) induces ROS-mediated apoptosis and cell cycle arrest in A549 human lung cancer cell line

Mechanistic insights into xanthomicrol as the active anti-HCC ingredient of Phytolacca acinosa Roxb.: A network pharmacology analysis and transcriptomics integrated experimental verification

Ethnopharmacological relevancePhytolacca acinosa Roxb. (PAR) is a Traditional Chinese Medicinal (TCM) plant with a broad global distribution encompassing 35 species, four of which are found in the People's Republic of China. It occupies a significant role in both Oriental and American traditional medicine, employed in treating a range of conditions such as edema, inflammation, dermatitis, and rheumatism. PAR is also used as a molluscicide and for addressing tumors and bronchitis. The plant is documented in the Chinese Pharmacopoeia and has a longstanding history in TCM, particularly for its diuretic properties and in treating ailments such as edema, swelling, and ulcers. Notably, PAR has demonstrated potent inhibitory effects against the A549 human lung cancer cell line, underscoring its potential in contributing to the development of novel cancer therapeutics. Aim of the studyThe research aims to elucidate the active components of PAR and their mechanisms in treating hepatocellular carcinoma (HCC). Materials and methodsEmploying network pharmacology, this study predicted the principal active compounds and key targets of PAR. A holistic methodology incorporating biological network analysis, transcriptomics sequencing, molecular docking, and molecular dynamics (MD) simulations was utilized to forecast the effects of PAR on HCC, with empirical evidence supporting these findings. ResultsNetwork pharmacology identified xanthomicrol as the foremost active compound in PAR. The tumor-suppressive functions of PAR, as indicated by KEGG pathway analysis and transcriptomics sequencing, predominantly occur via the PI3K/AKT pathway. Molecular docking and dynamics simulations demonstrated the high affinity of xanthomicrol towards TNF, MMP9, PPARG, KDR, and MMP2. In vivo experiments verified the efficacy of xanthomicrol in curtailing HCC tumor growth, while in vitro assessments revealed its substantial impact on the proliferation and apoptosis of HepG2 and HCCLM3 cells. Moreover, the study indicates that xanthomicrol may modulate the expression of TNF, MMP9, PPARG, KDR, and MMP2 in HCC cells and inhibit the activation of the PI3K/AKT pathway. ConclusionsXanthomicrol, a principal active component of PAR, has been identified to impede the growth of HCC by targeting the PI3K/Akt/MMP9 pathway. This insight could enhance therapeutic approaches for HCC.

Design, synthesis and apoptotic activity of substituted chalcones tethered 1,3,5-triazine hybrids: An insights from molecular docking, molecular dynamics simulations, DFT, ADME, and DAPI analyses

A novel library of chalcone tethered 1,3,5-triazine hybrids (5a-j) were designed and synthesized and their structures were confirmed by using spectroscopic/analytical techniques. The anticancer activity of the synthesized novel derivatives (5a-j) was evaluated against four human cancer cell lines: PC3 (Prostate cancer), A549 (Lung cancer), MCF7 (Breast cancer), and Colo-205 (Colon cancer) by employing of MTT assay method. In comparison to “Etoposide”, all the compounds showed excellent to moderate activity. The IC50 values of the novel derivatives (5a-j) ranged from 0.01±0.0032 µM to 12.4 ± 6.18 µM whereas positive control (Etoposide) showed 0.14±0.017 µM to 3.08±0.135 µM respectively. The newly developed substituted chalcone linked triazine hybrids were found to be good alternative anticancer agents. Among the all, (5a-j), mainly 5a, 5e, 5f, 5 g and 5j displayed highly potent anticancer activity towards MCF7 (5a), A549 (5 g), PC3 (5e, 5f) and Colo-205 (5j) human cancer cell lines. Principally, two compounds 5a and 5e were displayed as the most promising activities. The apoptotic mechanism in anticancer activity was further confirmed by nuclear staining analysis on more active test compounds 5a and 5e by DAPI (4′,6-diamidino-2-phenylindole) at different concentrations with MCF-7 cells, Additionally, all the synthesized compounds were investigated by molecular docking simulation studies with topoisomerase-IIβ enzyme (PDB ID: 3QX3) protein to correlate the in-vitro biological activity data evaluated on four human cancer cell lines. The docking scores of the newly produced conjugates (5a-j) varied from – 7.52 kcal/mol to -6.27 kcal/mol, indicating these compounds serve as an inhibitor. Human oral absorption is expected to be greater than 75 %. The in-vitro cytotoxicity behavior of tested compounds was further supported by in-silico predictions such as ADME, MD simulations and DFT studies.

Ionizing Radiation-treated NRF2-deficient Cancer Cells Promote Type I Interferon Signaling in Immune Cells.

Nuclear factor erythroid-derived 2-related factor-2 (NRF2) is a transcription factor that regulates stress response genes. It negatively regulates the immune system by acting as a transcriptional repressor of inflammatory genes or suppressing type I interferon (IFN) production pathways. NRF2 is often over-expressed in some tumors, including non-small cell lung cancer, and modulates these tumors via an immune-cold microenvironment. Thus, strategies to convert cold tumors into hot tumors are effective for cancer treatment. NRF2 was knocked-down or over-expressed in human cancer cells (A549, HeLa, H1299, H1650) and mouse mammary adenocarcinoma TS/A cells. Cells were irradiated or transfected with poly(I:C), and changes in type I IFN levels were examined using quantitative real-time polymerase chain reaction and western blotting. Cytosolic DNA was assayed via PicoGreen staining and immune and cancer cells were co-cultured. Regulation of NRF2 expression altered type I IFN levels in the human lung cancer cell line A549 and several solid tumors. Down-regulation of NRF2 resulted in increased levels of cytosolic DNA and activated the cGAS-STING pathway. We confirmed that type I IFN was induced in NRF2-down-regulated tumor cells using ionizing radiation (IR). Furthermore, when dendritic cells and macrophages were co-cultured with IR-exposed NRF2 knockdown tumor cells, the immune cells produced more IFNB1 and CXCL10. The immunosuppressive tumor cell environment is improved by NRF2 down-regulation, and IR treatment may promote immune cell signaling activation.

Synergistic anticancer effects of SMYD2 inhibitor BAY-598 and doxorubicin in non-small cell lung cancer

BackgroundNon-small cell lung Cancer (NSCLC) persists as a lethal neoplastic manifestation, exhibiting a diminished 5-year survival rate, partially attributable to chemotherapeutic resistance. This investigative endeavor aimed to elucidate the synergistic antineoplastic effects and underlying mechanisms of the SMYD2 inhibitor BAY-598 and the chemotherapeutic agent doxorubicin (DOX) in NSCLC. MethodsThe human non-small cell lung cancer cell lines A549 and H460 were subjected to treatment regimens involving BAY-598 and/or DOX. Cellular viability, apoptotic events, invasive capacity, and migratory potential were evaluated through the implementation of CCK-8 assays, flow cytometric analyses, and Transwell assays, respectively. Protein expression levels were quantified via Western blot analyses. An in vivo xenograft murine model was established to assess therapeutic efficacy. ResultsBAY-598 and DOX synergistically suppressed the viability, invasiveness, and migratory capabilities of NSCLC cells. Co-treatment Promoting cell apoptosis and cell cycle arrest. Additionally, Furthermore, co-administration significantly inhibited cell migration and invasion. Mechanistic studies revealed coordinately inhibited JAK-STAT signaling upon combination treatment. In vivo study further validated the synergistic antitumor efficacy of BAY-598 and DOX against NSCLC xenografts. ConclusionsOur findings demonstrate that BAY-598 potentiates the anti-cancer effects of DOX in non-small cell lung cancer cells by modulating the JAK/STAT signaling pathway as a synergistic strategy. The combination holds promise as an emerging therapeutic strategy for NSCLC. Further optimization and validation are warranted to promote its translational potential.

Macrophorins H and L, two new HMG-conjugate macrophorins from rihzospheric Penicillium sp. NX-05-G-3

Macrophorins H (4) and L (5), two rare HMG-conjugate macrophorins along with three known macrophorins (1-3), three DMOA-derived meroterpenoids (6-8) and two ergosterol derivates (9-10) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC50 values ranging from 17.6 to 32.8 µM.

Discovery of new eremophilanes from the marine-derived fungus Emericellopsis maritima BC17 by culture conditions changes: evaluation of cytotoxic and antimicrobial activities

In our previous studies, the marine-derived fungus Emericellopsis maritima BC17 was found to produce new eremophilane-type sesquiterpenoids on solid media. In order to explore its potential to produce more metabolites, E. maritima BC17 was subjected to a one strain-many compounds (OSMAC) analysis leading to the discovery of three new eremophilanes (1-3) and fourteen known derivatives (4-17) in the liquid media Czapek Dox and PDB. Their structures were established by extensive analyses of the 1D and 2D NMR, and HRESIMS data, as well as ECD data for the assignment of their absolute configurations. Antitumoral and antimicrobial activities of the isolated metabolites 1, 3, 11, and 15 were investigated. PR toxin 3-deacetyl (15) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058 and Mia PaCa-2 human cancer cell lines with IC50 values ranging from 2.5 to 14.7 µM. In addition, 15 exhibited selective activity against methicillin-sensitive Staphylococcus aureus ATCC29213 at the highest concentration tested of 128 µg/mL.