Human Lung Cancer Cells Research Articles

Novel bibenzyl compound 8Ae induces apoptosis and inhibits glycolysis by detaching hexokinase 2 from mitochondria in A549 cells

In this paper, we investigated the anticancer effect and the mechanism of our newly synthesized bibenzyl 8Ae against human lung cancer A549 cells. Compound 8Ae could induce apoptosis by inhibiting the glycolysis in A549 cells. Hexokinase 2 (HK2), the first key enzyme in glycolysis process, was significantly down-regulated by 8Ae. Besides, compound 8Ae induced HK2 dissociated from mitochondria to cytosol, which could be induced by inhibiting the phosphorylation of Akt. In addition, 8Ae could induce mitochondrial-mediated apoptosis, and mitochondrial membrane potential (MMP) was decreased. After 8Ae treatment, the Bax/Bcl-2 ratio was increased and cytochrome c (Cyt c) was release from mitochondria to cytosol. Molecular docking indicated that 8Ae have an interaction with HK2 by extending into acitve pockets of the protein to form stable hydrogen bonds. Additionally, 8Ae had significantly improved pharmacokinetic properties through the prediction, comparison, and analysis of the ADMET properties of 8Ae and moscatilin (MST). Taken together, 8Ae might inhibit glycolysis by stimulating the shedding of HK2 from mitochondria and promoting mitochondria-regulated apoptosis to inhibit the proliferation of A549 cells. This article provides a research basis for bibenzyl compounds as new small molecule drugs for lung cancer.

Deciphering the effect of Potentilla fulgens root extract against healthy HUVEC cell line and cancer cell lines (A549 and SKOV-3)

BackgroundPotentilla fulgens, a highly valued indigenous medicinal herb grown in high altitudes of the Himalayan region with anticancer, hypoglycaemic, antibacterial, anti-inflammatory, and antiulcerogenic properties, are used in traditional systems of medicine. This study was aimed to investigate the effect of P. fulgens root extract, as one of the natural alternatives to chemotherapeutic drugs used in cancer treatment, on proliferation, apoptosis, and autophagy of human non-small cell lung cancer cell line (A549), human ovarian cancer cell line (SKOV-3), and healthy human umbilical vein endothelial cell line (HUVEC). MethodsAnti-proliferative effect was assessed by MTT assay. The expression of autophagy and apoptosis-related proteins was evaluated by western blotting. Total oxidant status (TOS) and total antioxidant capacity (TAC) test were determined using standard kit methods. ResultsOur results showed that the extract inhibited proliferation of HUVEC, A549, and SKOV-3 cells in a dose-dependent manner. MTT assay analysis revealed that the extract significantly (P<0.05) induced mortality in HUVEC, A549, and SKOV-3 cells. Western blot results revealed increased expression of NF-κB after the extract treatment but led to the down-regulation in Beclin-1, Bax, extracellular-signal-related kinase 1 and 2, Sequestosome-1, and Cleaved Casp-3 levels. Treatment groups showed an increase in TOS and TAC values in A549 and SKOV-3 cell lines, while HUVEC cell line showed an increase in TAC and a decrease in TOS values, compared to the control group. ConclusionsOur findings indicated that P. fulgens root extract inhibited the proliferation of healthy cells and cancer cells through cell cycle arrest, representing its limited application as therapeutic agent in cancer treatment.

Chemical Composition, In vitro and In silico Evaluation of Essential Oil Extracted from Mentha Piperita L. for Lung Cancer

Background: Mentha piperita, a naturally occurring herb, is utilized in medicinal formulations. It possesses abundant bioactive elements, including flavonoids and phenolic acid compounds,that exhibit various properties such as antioxidants, anti-inflammatory and anti-cancer. Objective: In the present study, chemical constituents of essential oil extracted from Mentha piperita were analyzed and identified through GC-MS. In vitro antiproliferative activity was performed on A549 lung cancer cell line lines. In silico study was conducted by Schrodinger’s Maestro’s software to identify chemical constituents in the plant as potential EGFR (Epidermal Growth Factor Receptors) inhibitors Methods: Hydro-distilled essential oil was analyzed by GC-MS to identify chemical components based on the retention index and mass fragmentation pattern, which was then tested for its antiproliferative activity by MTT assay against human lung cancer cell lines. All the identified constituents were investigated in silico for their affinity towards EGFR (Epidermal Growth Factor Receptors). Results: A total of thirty constituents were identified where D-carvone (56.69%), L-limonene (12.36%), squalene (3.36%), cis-carveol (2.93%), and α-amorphene (2.36%) were observed as major constituents of the essential oil. The essential mentha oil also exhibited antiproliferative activity against lung cancer cell lines with an IC50 value of 86.05 µg/ml. Furthermore, from the in silico study, five constituents were identified to have a better affinity for EGFR (Epidermal Growth Factor Receptors) than that of the standard drug Osimertinib. Conclusion: In the present study, the aerial part of the plant Mentha piperita was hydrodistilled.Thirty phytoconstituents were identified through GC-MS data. An in-silico study was performed using Schrodinger software, and a further in vitro study was performed in which essential oil showedgood antiproliferative activity against the A549 cancer cell line.

Antioxidant and Anti-Proliferative Effects of Ornithogalum balansae Extracts Collected in Black Sea Region Against Lung Cancer Cells

Ornithogalum is a genus of wild herb species widely used as food and in traditional medicine. This study investigated some of the biologically active properties of Ornithogalum balansae grown in the eastern Black Sea region of Türkiye. The investigations were carried out using the methanolic extracts of the plant’s aerial and bulbs (B1 and B2) parts. The phenolic composition was examined as total phenolic content (TPC), total flavonoid content (TFC), and HPLC-PDA. The antioxidant capacity of the extracts was tested based on ferric reducing/antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging methods. The anti-proliferative activity was tested against metastatic cell lines H1299 and H209, non-small-cell lung A549, and fibroblast MRC-5 cell lines using MTT and trypan blue methods. Wound-healing and invasion chamber assays were used to determine the inhibitory effects of the extracts on migration and invasion, respectively. The extract of the aerial part contained a large number of phenolic substances and high antioxidant capacity. The extract exhibited a significant anti-proliferative effect on the human lung cancer cells (A549 and H209), with IC50 values of 0.97 ± 0.04 and 1.06 ± 0.07 µg/mL, respectively. Moreover, the aerial part exhibited inhibition of migratory and invasive capacities in A549 cells at a concentration of 1.50 µg/mL. The findings associated with O. balansae suggest a promising therapeutic potential against lung cancer cells.

A splicing isoform of PD-1 promotes tumor progression as a potential immune checkpoint

The immune checkpoint receptor, programmed cell death 1 (PD-1, encoded by PDCD1), mediates the immune escape of cancer, but whether PD-1 splicing isoforms contribute to this process is still unclear. Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5′ region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes. PD-1^28 expression is induced on T cells upon activation and is regulated by an RNA binding protein, TAF15. Functionally, PD-1^28 inhibits T cell proliferation, cytokine production, and tumor cell killing in vitro. In vivo, T cell-specific exogenous expression of PD-1^28 promotes tumor growth in both a syngeneic mouse tumor model and humanized NOG mice inoculated with human lung cancer cells. Our study thus demonstrates that PD-1^28 functions as an immune checkpoint, and may contribute to resistance to immune checkpoint blockade therapy.

Synthesis of Sulfonamide-Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies.

The current study focuses on the synthesis and characterization of six benzenesulfonamide-based Schiff base derivatives (7-12) with various electron-withdrawing and electron-donating substituents (-F, -CI, -Br, -CH3, and -OCH3) and the assessment of their antiproliferative activities against human lung (A549) and liver (HepG2) cancer cell lines using in vitro and in silico approaches. The structures of the synthesized compounds (7-12) were elucidated by elemental analysis and FT-IR, 1D (1H, 13C, APT, and DEPT-135), and 2D (HMQC and HMBC) NMR spectroscopies. The cytotoxic activities of the targeted compounds were determined at various concentrations against these cancer cell lines for 72 h, using the MTT method. The targeted molecules (7-12) demonstrated remarkable antiproliferative activities, with IC50 values ranging from 6.032-9.533 μM against the A549 cell line and 5.244-9.629 μM against the HepG2 cell line. These compounds showed activities at lower or very similar concentrations to cisplatin against the A549 cell line and at much lower concentrations than cisplatin against the HepG2 cell line. Among them, compounds 10 and 12 were found to be more effective against A549 and HepG2 cells, respectively, than cisplatin. These compounds were analyzed by interacting with the 1BNA, 4HJO, and 4ASD crystal structures in molecular docking studies.

Nerolidol inhibits proliferation and triggers ROS-facilitated apoptosis in lung carcinoma cells via the suppression of MAPK/STAT3/NF-κB and P13K/AKT pathways.

Lung cancer (LC) is the leading cause of malignancy-related mortalities globally, and the existing treatment interventions are associated with harmful side effects. In the current study, we evaluated the anti-tumor efficiency of nerolidol (NRD) on human non-small cell lung cancer (NSCLC) cells. Nerolidol is a sesquiterpene alcohol extracted from the essential oils of aromatic flora with known anti-cancer activities. The latent action of NRD on antiproliferative and apoptotic effects in A549 cells is uncertain. Thus, our work is designed to explore the antiproliferative and apoptotic actions of NRD (20 and 25 μM/mL) against A549 cells. The activity of NRD on A549 cell cytotoxicity, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis, anti-apoptotic proteins, and MAPK/TAT3/NF-κB and P13K/AKT signaling pathways were assessed using MTT tests, dichlorodihydrofluorescein diacetate (DCFH-DA), dual acridine orange/ethidium bromide (AO/EB), DAPI, Rh-123, reverse transciption polymerase chain reaction (RT-PCR), and western blot analyses. We found that NRD could inhibit NSCLC cell viability through elevated intracellular ROS and MMP loss and elicited apoptosis in a quantity-dependent manner. Similarly, NRD can reduce inflammatory cytokines and anti-apoptotic elements, as well as trigger apoptotic signaling pathways. Our data established that NRD decreases A549 cell proliferation through ROS-mediated apoptosis, triggering the MAPK/STAT3/NF-κB and P13K/AKT pathways, suggesting that NRD is a possible protective remedy for NSCLC.

Exploring the 3,5-Dibromo-4,6-dimethoxychalcones and Their Flavone Derivatives as Dual α-Glucosidase and α-Amylase Inhibitors with Antioxidant and Anticancer Potential.

The rising levels of type 2 diabetes mellitus (T2DM) and the poor medical effects of the commercially available antidiabetic drugs necessitate the development of potent analogs to treat this multifactorial metabolic disorder. It has been demonstrated that targeting two or more biochemical targets associated with the onset and progression of diabetes along with oxidative stress and/or cancer could be a significant strategy for treating complications related to this metabolic disorder. The 3,5-dibromo-4,6-dimethoxychalcones (2a-f) and the corresponding flavone derivatives (3a-f) were synthesized and characterized using spectroscopic (NMR, HR-MS and FT-IR) techniques. The inhibitory effect of both series of compounds against α-glucosidase and α-amylase was evaluated in vitro through enzymatic assays. Selected compounds were also evaluated for potential to activate or inhibit superoxide dismutase. Compound 3c was selected as a representative model for the flavone series and evaluated spectrophotometrically for potential to coordinate Cu(II) and/or Zn(II) ions implicated in the metal-catalyzed free radical generation. A plausible mechanism for metal-chelation of the test compounds is presented. Furthermore, the most active compounds from each series against the test carbohydrate-hydrolyzing enzymes were selected and evaluated for their antigrowth effect on the human breast (MCF-7) and lung (A549) cancer cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The parent chalcone 2a and flavone derivatives 3a, 3c and 3e exhibited relatively high inhibitory activity against the MCF-7 cells with IC50 values of 4.12 ± 0.55, 8.50 ± 0.82, 5.10 ± 0.61 and 6.96 ± 0.66 μM, respectively. The chalcones 2a and 2c exhibited significant cytotoxicity against the A549 cells with IC50 values of 7.40 ± 0.67 and 9.68 ± 0.80 μM, respectively. Only flavone 3c exhibited relatively strong and comparable cytotoxicity against the MCF-7 and A549 cell lines with IC50 values of 6.96 ± 0.66 and 6.42 ± 0.79 μM, respectively. Both series of compounds exhibited strong activity against the MCF-7 and A549 cell lines compared to the analogous quercetin (IC50 = 35.40 ± 1.78 and 35.38 ± 1.78 μM, respectively) though moderate compared to nintedanib (IC50 = 0.53 ± 0.11 and 0.74 ± 0.15 μM, respectively). The test compounds generally exhibited reduced cytotoxicity against the Vero cells compared to this anticancer drug. Molecular docking revealed strong alignment of the test compounds with the enzyme backbone to engage in hydrogen bonding interaction/s and hydrophobic contacts with the residues in the active sites of α-glucosidase and α-amylase. The test compounds possess favorable drug-likeness properties, supporting their potential as therapeutic candidates against T2DM.

Banana fruit (Musa sp.) DNA-magnetite nanoparticles: Synthesis, characterization, and biocompatibility assays on normal and cancerous cells.

Magnet-mediated gene therapy has gained considerable interest from researchers as a novel alternative for treating genetic disorders, particularly through the use of superparamagnetic iron oxide nanoparticles (NPs)-such as magnetite NPs (Fe3O4NPs)-as non-viral genetic vectors. Despite their commercial availability for specific genetic transfection, such as in microglia cell lines, many potential uses remain unexplored. Still, ethical concerns surrounding the use of human DNA often impede genetic research. Hence, this study examined DNA-coated Fe3O4NPs (DNA-Fe₃O₄NPs) as potential transfection vectors for human foreskin fibroblasts (HFFs) and A549 (lung cancer) cell lines, using banana (Musa sp.) as a low-cost, and bioethically unproblematic DNA source. Following coprecipitation synthesis, DNA-Fe₃O₄NP characterization revealed a ζ-potential of 40.65 ± 4.10 mV, indicating good colloidal stability in aqueous media, as well as a superparamagnetic regime, evidenced by the absence of hysteresis in their magnetization curves. Successful DNA coating on the NPs was confirmed through infrared spectra and surface analysis results, while magnetite content was verified via characteristic X-ray diffraction peaks. Transmission electron microscopy (TEM) determined the average size of the DNA-Fe3O4NPs to be 14.69 ± 5.22 nm. TEM micrographs also showed no morphological changes in the DNA-Fe3O4NPs over a 30-day period. Confocal microscopy of HFF and A549 lung cancer cell lines incubated with fluoresceinamine-labeled DNA-Fe3O4NPs demonstrated their internalization into both the cytoplasm and nucleus. Neither uncoated Fe3O4NPs nor DNA-Fe3O4NPs showed cytotoxicity to A549 lung cancer cells at 1-50 μg/mL and 25-100 μg/mL, respectively, after 24 h. HFFs also maintained viability at 1-10 μg/mL for both NP types. In conclusion, DNA-Fe3O4NPs were successfully internalized into cells and exhibited no cytotoxicity in both healthy and cancerous cells across a range of concentrations. These NPs, capable of binding to various types of DNA and RNA, hold promise for applications in gene therapy.

One-pot synthesis of fused isoxazolo[4′,5′:4,5]thiopyrano[2,3-d]pyrimidines as potent EGFR targeting anti-lung cancer agents

The requirement for scaffolds has prompted synthetic chemists to devise simple and effective methods for optimal synthesis, which are critical in the medical industry. Under comparatively optimized conditions, a click followed by a CC bond coupling reaction between iodoalkyne (4) and substituted nitrile oxide was utilized to explore the synthesis of fused isoxazoles containing thiopyrano[2,3-d]pyrimidine under microwave irradiation. The synthesized compounds were tested for their anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H460 and A549). The compounds 6i and 6l have shown more potent activity against both cancer cell lines as compared to standard drugs doxorubicin and erlotinib. And also compounds 6e, 6j, and 6k have shown more potent activity as compared to Doxorubicin and moderate activity compared to erlotinib. Later, in vitro EGFR results of more potent compounds revealed that compounds 6l and 6k have shown potent EGFR activity compared to standard erlotinib. To evaluate the molecular interactions of more potent compounds with the human epidermal growth factor receptor. It was observed that all the potent compounds exhibited greater binding energies in comparison to the standard drug erlotinib.

Isoquercitrin Inhibits Lung Cancer Cell Growth Through Triggering Pyroptosis and Ferroptosis

Isoquercitrin possesses anti-tumor activity in several types of cancers, however, its effects and underlying mechanisms on lung cancer have not been reported. Human lung cancer cell lines as well as normal lung epithelial BEAS-2B cells were treated with isoquercitrin. The influences of isoquercitrin in vitro were evaluated by determining cell viability, apoptosis, pyroptosis, and ferroptosis. Additionally, A549 tumor-bearing mice were generated to explore the anti-cancer effect of isoquercitrin in vivo. We found that isoquercitrin dose-dependently reduced lung cancer cells’ viability, with no toxicity against BEAS-2B cells. Isoquercitrin at 40 μM and 80 μM was used in vitro. Isoquercitrin increased apoptosis, elevated NLRP3 inflammasome activation-mediated pyroptosis, and promoted ferroptosis in lung cancer cells. NLRP3 knockdown and caspase-1 selective inhibitor VX-765 attenuated isoquercitrin-induced pyroptosis and ferroptosis, but not apoptosis. Furthermore, isoquercitrin accelerated ROS generation, while ROS inhibitor N-acetylcysteine abrogated isoquercitrin-induced apoptosis, NLRP3 related-pyroptosis and ferroptosis. In vivo, isoquercitrin (1 mg/kg and 5 mg/kg) inhibited tumor growth, increased apoptosis, NLRP3-related pyroptosis, ferroptosis and ROS generation in tumors. Taken together, isoquercitrin inhibits lung cancer growth by triggering ROS/NLRP3-mediated pyroptosis and ferroptosis, with ROS also directly inducing apoptosis. This suggests that isoquercitrin might be a potential therapeutic agent for lung cancer.

Mutations of the Cx43 Gene in Non-Small Cell Lung Cancer: Association with Aberrant Localization of Cx43 Protein Expression and Tumor Progression

Background and Objectives: The Connexin43 (Cx43) gene is a suspected tumor suppressor gene, as re-expressed wild-type Cx43 genes reduce the malignancy potential of tumor cells. However, the role of Cx43 gene expression in human lung tumorigenesis remains unclear. Materials and Methods: Tumor tissues from 165 primary lung cancer patients were collected to study Cx43 protein expression and gene mutations using immunohistochemistry and direct DNA sequencing. In addition, Cx43 genes with or without mutations were transfected to CL-3 human lung cancer cells to confirm the function of these mutant forms of the Cx43 gene. Results: Aberrant localization of Cx43 protein in the nucleus and cytoplasm of tumor cells was detected in 14 out of 165 non-small cell lung cancer (NSCLC) patients. Mutations in the Cx43 gene were also found in patients with aberrant Cx43 localization, and transfection of these mutant genes into lung cancer cells enhanced their proliferation. Conclusions: To our knowledge, this is the first study to demonstrate Cx43 gene mutations in human lung neoplasm, supporting the hypothesis that Cx43 may function as a tumor suppressor in some lung cancer patients. Additionally, the findings suggest an association between aberrant localization of Cx43 protein expression and tumor progression.

Design, synthesis and antitumor effects of lupeol quaternary phosphonium salt derivatives

Lupeol is a natural pentacyclic triterpenoid with a wide range of biological activities. To improve the water solubility and targeting of lupeol, in the following study, we synthesized 27 lupeol derivatives in the first series by introducing lipophilic cations with lupeol as the lead compound. Through the screening of different cancer cells, we found that some of the derivatives showed better activity than cisplatin against human non-small cell lung cancer A549 cells, among which compound 6c was found to have an IC50 value of 1.83 μM and a selectivity index of 21.02 (IC50MRC-5/IC50A549) against A549 cells. To further improve the antiproliferative activity of the compounds, we replaced the ester linkage of the linker with a carbamate linkage and synthesized a second series of five lupeol derivatives which were screened for activity, among which compound 14f was found to have an IC50 value of 1.36 μM and a selectivity index of 15.60 (IC50MRC-5/IC50A549) against A549 cells. We further evaluated the bioactivity of compounds 6c and 14f and found that both compounds induced apoptosis in A549 cells, promoted an increase in intracellular reactive oxygen species and decrease in mitochondrial membrane potential, and inhibited the cell cycle in the S phase. Of the compounds, compound 14f showed stronger bioactivity than compound 6c. We then selected compound 14f for molecular-level Western blot evaluation and in vivo evaluation in the zebrafish xenograft A549 tumor cell model. Compound 14f was found to significantly downregulate Bcl-2 protein expression and upregulate Bax, Cyt C, cleaved caspase-9, and cleaved caspase-3 protein expression, and 14f was found to be able to inhibit the proliferation of A549 cells in the zebrafish xenograft model. The above results suggest that compound 14f has great potential in the development of antitumor drugs targeting mitochondria.

Hydrazone-Functionalized trans-A2B-Corroles: Effective Synergy in Photodynamic Therapy of Lung Cancer.

A synthetic route to trans-A2B-corroles combining the macrocyclic core with a hydrazone moiety, based on the reactivity of azoalkenes toward dipyrromethanes, has been established with the aim of developing a new class of photosensitizers for photodynamic therapy of lung cancer. The study of the photophysical properties of the novel macrocycles allowed the identification of photosensitizers with absorption within the phototherapeutic window and high singlet oxygen quantum yield. Relevant structure-photodynamic activity correlations were established by studying the new corroles-based photodynamic therapy (PDT) in human lung cancer cell lines (A549 and H1299). The methyl-hydrazone corroles were more active than phenyl-hydrazone corroles, with the N-Boc and N-Ts groups being key structural features to ensure high activity. The lead photosensitizers, with IC50 values below 100 nM and no cytotoxicity per se, were significantly more active than 5,10,15-triphenylcorrole, showing that the presence of the hydrazone functional group has a strong influence on PDT activity.

Chemical composition and biological activities of nine essential oils obtained from Algerian plants

The essential oils (EOs) from nine species (Artemisia campestris, A. herba-alba, Juniperus foetidissima, Laurus nobilis, Mentha pulegium, M. spicata, Rosmarinus officinalis, Salvia officinalis, and Thymus vulgaris) of the Algerian flora have been hydrodistilled, analysed, and tested for their antioxidant and antiproliferative properties. A. campestris EO showed a higher content of terpene hydrocarbons; A. herba-alba EO was mainly rich in their oxygenated derivatives. Sesquiterpenes were the most abundant compounds in J. foetidissima EO, while oxygenated monoterpenes and phenylpropanoids prevailed in L. nobilis EO. The other EOs were rich in oxygenated monoterpenes, with quality–quantitative differences. T. vulgaris and L. nobilis performed better in all the antioxidant assays, respectively with IC50 values ranging from 0.0002 and 0.0012 mg/mL in the CUPRAC assay to 2.83 and 3.50 mg/mL in the FRAP assay. T. vulgaris was also the only EO exhibiting an antiproliferative activity towards the human breast (MCF-7) and lung (A549) cancer cell lines.

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 &amp; 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 &amp;gt;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.

Nano-synthesis, characterization, theoretical, biological and catalytic studies of Mn(II), Cu(II), Cd(II), and Th(IV) complexes based on antipyrine azo dye ligand

The design and detailed characterization of the azo dye ligand obtained from the reaction of 4-aminoantipyrine diazonium salt with 3-hydroxybenzaldehyde (HL) and its novel metal chelates with Mn2+, Cu2+, Cd2+ and Th4+ ions have been presented. Utilizing modern spectroscopic and analytical techniques, these complexes were found to adopt an octahedral geometry, demonstrate inner sphere d2sp3 hybridization for Th(IV) complex and outer sphere sp3d2 hybridization for other complexes. Particle sizes calculated using the Debye-Scherrer equation on XRD patterns were 32.05 nm for Mn(II), 34.07 nm for Cu(II), 30.90 nm for Cd(II), and 22.05 nm for Th(IV). These substances' anticancer activity was assessed on human lung cancer cells (A-549) and pancreatic carcinoma cell lines (PANC-1). Cd(II) complex exhibited higher cytotoxicity against the A-549 cell line than the reference drug vinblastine sulfate which revealing its potential application as a new anticancer agent. Quantum chemical computations using the DMOL3 module's density functional theory (DFT) and molecular docking studies with the Schrödinger suite demonstrated significant inhibitory effects of the free organic compound and Cu(II) chelate on the FGFR1 protein, crucial for cell development and differentiation. Additionally, the study examined the catalytic activity of HL and its metal chelates in the oxidative degradation of methyl violet 2B dye in presence of H2O2. The order was followed by the pseudo-first-order rate constants: Th(IV) chelate (0.9556 min⁻¹) > HL (0.4911 min⁻¹) > Cu(II) chelate (0.5979 min⁻¹) > Mn(II) chelate (0.2645 min⁻¹) > Cd(II) chelate (0.2280 min⁻¹).

Iridoids and lignans from Valeriana officinalis and their bioactivities

Seven undescribed iridoids, identified as valeriridoids A-E (compounds 1, 5, 18, 19a, 19b, 20a, and 20b), were isolated from the roots and rhizomes of Valeriana officinalis L., along with sixteen known iridoids and nine known lignans. The structures were elucidated using NMR and MS spectroscopy, and the absolute configurations of the undescribed iridoids were determined through ECD calculations. Valeriridoids D and E were found to be epimeric and scalemic mixtures, which were successfully resolved through a chiral column. These isolated iridoids were evaluated for their antiproliferative activities, with valeriridoid A, jatamanvaltrates P, and Q showing significant effects against human non-small cell lung cancer cells, with IC50 values of 14.68, 8.77, and 10.07 μM, respectively. Furthermore, the antihyperglycemic properties of the compounds were investigated in insulin-resistant human hepatoblastoma cells induced by palmitic acid treatment, revealing that valeriridoid A, jatamanvaltrates P, and Q at a concentration of 10 μM led to a notable increase in glucose consumption.

A Novel Tryptanthrin Derivative D6 Induces Apoptosis and DNA Damage in Non-small-cell Lung Cancer Cells Through Regulating the EGFR Pathway.

Non-small-cell lung cancer is a prevalent malignancy associated with significant morbidity and mortality rates. Tryptanthrin and its derivatives have exhibited potent antitumor activity. This study aims to investigate the inhibitory effect of a novel synthesized tryptanthrin derivative D6 on proliferation and the possible mechanism of human non-small cell lung cancer cell lines (A549) in vitro. In this study, MTT assay, cell migration, colony formation assay, cell cycle analysis, cell apoptosis, JC- 1 staining assay, reactive oxygen species analysis, proteomics, western blotting, high content screening and absorption titrations analysis were performed. We found that D6 inhibited both the proliferation and migration, induced cell cycle arrest in the G2/M phase, increased levels of ROS, decreased mitochondrial membrane potential, and promoted apoptosis in A549 cells. Further mechanistic studies found that D6 reduced EGFR expression in A549 cells and inhibited the EGFR pathway by decreasing phosphorylation levels of EGFR, Stat3, AKT and Erk1/2. Moreover, DNA damage induced by D6 involved an increase in p53/MDM2 ratio and concentration-dependent accumulation of micronuclei. D6 demonstrated significant antitumor activity against A549 cells by inhibiting the EGFR signaling pathway, inducing DNA damage, and subsequently leading to oxidative stress, apoptosis, and cell cycle arrest. Our findings suggest that D6 exhibits potential as an NSCLC drug, owing to its attributes such as antiproliferative activity and ability to induce apoptosis by attenuating the EGFR-mediated signaling pathway.