Anti-lung Cancer Activity Research Articles

Effect of fermentation on the constituents in the branches and leaves of Taxus media and non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a prominent lung cancer disease worldwide. Currently, commonly used methods, such as surgery and radiotherapy, have significant side effects. Traditional Chinese medicine (TCM) has become a research hotspot because of its safe and effective characteristics. The branches and leaves of Taxus media are abundant in antitumor active compounds, and there has been no research conducted as yet regarding its anti-lung cancer molecular mechanism. The aim of this study is to investigate the antitumor activity of two samples before and after fermentation of T. media, and to research the molecular mechanism of its inhibitory effect on NSCLC. The chemical composition of pre-fermentation T. media (TM) and post-fermentation T. media qu (TMQ) were investigated using UHPLC-Q-Qrbitrap HRMS and high-performance liquid chromatography (HPLC). The anti-lung cancer activities of TM and TMQ were compared using an A549-induced tumor mouse model. An enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were used to determine the of TMQ mechanism of action. The results indicated that TM and TMQ contained 83 compounds, consisting primarily of flavonoids, organic acids, and taxanes. Both taxanes and flavonoids in TMQ were higher than that in TM. Both TM and TMQ effectively inhibited the tumor growth in non-small cell lung cancer (NSCLC), and the inhibition rate was greater in TMQ (57.24%) than in TM (49.62%). TMQ administration downregulated the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the glutathione (GSH) level and upregulated interferon-γ (IFN-γ), reactive oxygen species (ROS), and malondialdehyde (MDA) levels in the serum of tumor mice. TMQ treatment also increased the protein expression of Bax, Caspase-3, and Beclin-1 in tumor tissues. In contrast, the bcl-2, PI3K, Ki67, ULK1, and mTOR protein levels were suppressed by TMQ. Protein assay analyses reemphasized the superior antitumor effect of TMQ over TM. These cumulative findings demonstrated that the mechanism of action of TMQ was closely related to the activation of transcriptional misregulation in the cancer pathway that inhibited the cholinergic synaptic, AMPK, and PI3K/Akt/mTOR signaling pathways. This study demonstrated that fermentation increased the active ingredient contents and antitumor effects of T. media. In addition, post-fermentation TMQ was superior to TM as a herbal medicine for NSCLC treatment.

Statement of Retraction: Synthesis, characterization and anti-lung cancer activity of two transition metal coordination polymers based on the imidazole-containing ligands

Statement of Retraction: Synthesis, characterization and anti-lung cancer activity of two transition metal coordination polymers based on the imidazole-containing ligands

Anti-inflammatory and anti–lung cancer activities of low-molecular-weight and high-sulfate-content sulfated polysaccharides extracted from the edible fungus Poria cocos

Sulfated polysaccharides (SPSs) have excellent physicochemical properties, attracting research interest in the pharmaceutical industry. A previous study extracted SPS (named Suc40) from the edible fungus, Poria cocos and demonstrated that it exhibited anti-inflammatory and anticancer activities. In this study, three fractions of Suc40, Suc40 F1, Suc40 F2, and Suc40 F3, with different molecular weights and sulfate contents were prepared through gel-filtration column chromatography. The molecular weights of F1, F2, and F3 were approximately 616.23, 82.57, and 6.21 kDa, respectively, and their sulfate content were 0.23, 1.65, and 1.90 mmol/g, respectively. The fractions' anti-inflammatory activities were determined by assessing their ability to suppress inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Suc40 F2 and Suc40 F3 suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production by 60 % and 35 %, respectively. Suc40 F2 and Suc40 F3 suppressed protein kinase B (AKT)/p38 and p38 signaling, which resulted in anti-inflammatory effects. The fractions' anti–lung cancer activity was evaluated by assessing their H1975 cell proliferation inhibition. Suc40 F3 at a concentration of 800 μg/ml exhibited maximal cell proliferation inhibition. The low molecular weight and high sulfate content of Suc40 F3 were associated with its enhanced anti-inflammatory and anti–lung cancer activities.

Anti-Lung Cancer and Cell Migration Inhibition Properties of Ethyl Acetate Extract of Selaginella doederleinii Towards HTB-183 Cells through In Silico and In Vitro Approach

Continuous research and development to obtain novel anti-lung cancer agents is essential, considering the high prevalence and mortality of the disease. The biflavonoid compounds of Selaginella doederleinii showed significant anticancer activities. This study aims to determine the cytotoxic and cell migration inhibition properties of ethyl acetate extract of Selaginella doederleinii (EAESD) against HTB-183 cells through in silico and in vitro methods. This study started with extraction and then identified biflavonoids in EAESD by HPLC. In vitro analysis was conducted through MTT Assay to observe the cytotoxic properties of EAESD and Wound Scratch Healing Assay to observe its cell migration inhibitory properties. In silico studies to obtain the potential anti-lung cancer compounds and their protein targets were conducted through bioinformatics, combining PASS analysis, Swiss Target Prediction, and STITCH. The obtained compounds and protein targets were analyzed in Molecular Docking to evaluate the binding affinities. The result showed that EAESD contained biflavonoid compounds, exhibited cytotoxic activity with an IC50 value of 190 μg/ml, and inhibited the migration rate of HTB-183 cells. Based on in silico analysis, the three biflavonoids with the highest potential of antilung cancer activity along with their target protein are robustaflavone 7,4-dimethyl ether with EGFR, heveaflavone with ESR1, and 7,4',7'',4'''-tetra-O-methyl-amentoflavonewith TNF. All compounds can bind to each protein target with the docking score -9.2 kcal/mol, -9.5 kcal/mol, and -6.5 kcal/mol, respectively. This study suggested preliminary data regarding the potential of Selaginella doederleinii to inhibit the proliferation and migration of the HTB-183 cell line of lung cancer.Keywords: Selaginella doederleinii, HTB-183, cytotoxicity, cell migration, in silico analysis.

Exploring the anti-lung cancer mechanism of Ganoderma lucidum and its relationship with the level of immune cell infiltration based on network pharmacology and molecular docking

Abstract Objectives Ganoderma lucidum has anti-tumor effects, but its mechanism of action against lung cancer is not clear. This study aims to use molecular docking and network pharmacology to investigate how G. lucidum inhibits tumor growth in lung cancer and how this relationship relates to the degree of immune cell infiltration. Methods By utilizing the TCMSP database, the therapeutic targets and active ingredients of G. lucidum were discovered. Based on the targets found in subsequent rounds of screening, a protein interaction (PPI) network was constructed. Additionally, enrichment analysis was conducted using GO and the KEGG. The molecular docking was conducted with the help of AutoDock Tools and PyMOL. Finally, we investigated the relationships between immune cells and the commonalities between lung cancer and. Results The primary targets of G. lucidum’s anti-lung cancer activities, according to network pharmacology studies, are ADRB2, OPRM1, SLC6A4, and JUN. The primary components of the lung cancer fighter Ergosterol are ganoderal B, ganolucidic acid E, and beta-sitosterol. The molecular docking analysis revealed that beta-sitosterol had the highest degree of stability in its docking interaction with JUN. The immune infiltration analysis indicated a potential correlation between the biomarkers associated with G. lucidum treatment for lung cancer and the immune infiltrating cells. Conclusions G. lucidum combats lung cancer by targeting multiple components and signaling pathways, facilitating cancer cell apoptosis and interacting with immune responses. This elucidates potential avenues for future research into G. lucidum’s mechanisms in lung cancer therapy.

Imidazo[1,2-a]pyridine-appended chalcone and Schiff base conjugates: Synthetic, spectrophotometric, biological, and computational aspects

Herein we describe 2-chloroimidazo[1,2-a]pyridine-appended Schiff base and chalcone conjugates, exploring their synthetic, spectrophotometric, biological, and computational aspects. UV–visible study revealed that scaffolds VIc and VIIIa exhibit bathochromic and hypsochromic shifts respectively compared to their analogs, due to auxochrome effect. The molecular docking simulations were performed to investigate the binding interactions of motifs with three cancerous target proteins (4HJO, 1M14, and 1M17) and four microbial target proteins. The compound VIIIb exhibited significant anti-lung cancer activity (GI50: 22.3) against the A-459 cell line. Moreover, the synthesized compounds exhibited auspicious antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Klebsiella pneumoniae, with MIC ranging from 64 to 175 µg/mL. Additionally, in-silico target prediction analysis suggested a considerable likelihood (26.7%) of acting on kinases for compounds VIIIa and VIIIc. In-silico toxicity scrutiny anticipated all compounds as non-fatal and less toxic as they belong to toxicity class 4 (300 < LD50 ≤ 2000). Further structural insights into the synthesized compounds were gained through optimized geometries, FMOs, MEP plots, and global reactivity descriptors (µ, ɳ, S, and ω), aiding in understanding their structural features, potential reactivity, and toxicity. Overall, these results highlight the potential of the prepared moieties as hopeful intrants for further development.

Anticancer activity of Araguspongine C via inducing apoptosis, and inhibition of oxidative stress, inflammation, and EGFR-TK in human lung cancer cells: An in vitro and in vivo study.

The advanced non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor(EGFR) mutations has put a selective pressure on the discovery and development of newer EGFR inhibitors. Therefore, the presentstudy intends to explore the pharmacological effect of Araguspongine C (Aragus-C) as anticancer agent against lung cancer. The effect of Aragus-C was evaluated on the viability of the A549 and H1975 cells. Further biochemical assays were performed to elaborate the effect of Aragus-C, on the apoptosis, cell-cycle analysis, and mitochondrial membrane potential in A549 cells. Western blot analysis was also conducted to determine the expression of EGFR in A549 cells. Tumor xenograft mice model from A549 cells was established to further elaborate the pharmacological activity of Aragus-C. Results suggest that Aragus C showed significant inhibitory activity against A549 cells as compared to H1975 cells. It has been found that Aragus-C causes the induction of apoptosis and promotes cell-cycle arrest at the G2/M phase of A549 cells. It also showed a reduction in the overexpression of EGFR in A549 cells.In tumor xenograft mice model, it showed a significant reduction of tumor volume in a dose-dependent manner, with maximum inhibitory activity was reported by the 8 mg/kg treated group. It also showed significant anti-inflammatory and antioxidant activity by reducing the level of TNF-α, IL-1β, IL-6, and MDA, with a simultaneous increase of superoxide dismutase and glutathione peroxidase. We have demonstrated the potent anti-lung cancer activity of Aragus-C, and it may be considered as a potential therapeutic choice for NSCLC treatment.

In silico discovery of potential PPI inhibitors for anti-lung cancer activity by targeting the CCND1-CDK4 complex via the P21 inhibition mechanism.

Non-Small Cell Lung Cancer (NSCLC) is a prevalent and deadly form of lung cancer worldwide with a low 5-year survival rate. Current treatments have limitations, particularly for advanced-stage patients. P21, a protein that inhibits the CCND1-CDK4 complex, plays a crucial role in cell proliferation. Computer-Aided Drug Design (CADD) based on pharmacophores can screen and design PPI inhibitors targeting the CCND1-CDK4 complex. By analyzing known inhibitors, key pharmacophores are identified, and computational methods are used to screen potential PPI inhibitors. Molecular docking, pharmacophore matching, and structure-activity relationship studies optimize the inhibitors. This approach accelerates the discovery of CCND1-CDK4 PPI inhibitors for NSCLC treatment. Molecular dynamics simulations of CCND1-CDK4-P21 and CCND1-CDK4 complexes showed stable behavior, comprehensive sampling, and P21's impact on complex stability and hydrogen bond formation. A pharmacophore model facilitated virtual screening, identifying compounds with favorable binding affinities. Further simulations confirmed the stability and interactions of selected compounds, including 513457. This study demonstrates the potential of CADD in optimizing PPI inhibitors targeting the CCND1-CDK4 complex for NSCLC treatment. Extended simulations and experimental validations are necessary to assess their efficacy and safety.

3,5-DCQA as a Major Molecule in MeJA-Treated Dendropanax morbifera Adventitious Root to Promote Anti-Lung Cancer and Anti-Inflammatory Activities.

(1) Background: Phytochemicals are crucial antioxidants that play a significant role in preventing cancer. (2) Methods: We explored the use of methyl jasmonate (MeJA) in the in vitro cultivation of D. morbifera adventitious roots (DMAR) and evaluated its impact on secondary metabolite production in DMAR, optimizing concentration and exposure time for cost-effectiveness. We also assessed its anti-inflammatory and anti-lung cancer activities and related gene expression levels. (3) Results: MeJA treatment significantly increased the production of the phenolic compound 3,5-Di-caffeoylquinic acid (3,5-DCQA). The maximum 3,5-DCQA production was achieved with a MeJA treatment at 40 µM for 36 h. MeJA-DMARE displayed exceptional anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-induced RAW 264.7 cells. Moreover, it downregulated the mRNA expression of key inflammation-related cytokines. Additionally, MeJA-DMARE exhibited anti-lung cancer activity by promoting ROS production in A549 lung cancer cells and inhibiting its migration. It also modulated apoptosis in lung cancer cells via the Bcl-2 and p38 MAPK pathways. (4) Conclusions: MeJA-treated DMARE with increased 3,5-DCQA production holds significant promise as a sustainable and novel material for pharmaceutical applications thanks to its potent antioxidant, anti-inflammatory, and anti-lung cancer properties.

Thiosemicarbazone Mixed-Valence Cu(I/II) Complex against Lung Adenocarcinoma Cells through Multiple Pathways Involving Cuproptosis.

Induction of cuproptosis and targeting of multiple signaling pathways show promising applications in tumor therapy. In this study, we synthesized two thiosemicarbazone-copper complexes ([CuII(L)Cl] 1 and [CuII2CuI(L)2Cl3] 2, where HL is the (E)-N-methyl-2-(phenyl(pyridin-2-yl)methylene ligand), to assess their antilung cancer activities. Both copper complexes showed better anticancer activity than cisplatin and exhibited hemolysis comparable to that of cisplatin. In vivo experiments showed that complex 2 retarded the A549 cell growth in a mouse xenograft model with low systemic toxicity. Primarily, complex 2 kills lung cancer cells in vitro and in vivo by triggering multiple pathways, including cuproptosis. Complex 2 is the first mixed-valent Cu(I/II) complex to induce cellular events consistent with cuproptosis in cancer cells, which may stimulate the development of mixed-valent copper complexes and provide effective cancer therapy.

Integrated component identification, network pharmacology, and experimental verification revealed mechanism of Dendrobium officinale Kimura et Migo against lung cancer

BackgroundDendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PurposeThe objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. MethodsThe chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. Results249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. ConclusionsThis study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.

Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer

IntroductionBaicalein, a bioactive component of Scutellaria baicalensis Georgi, has been shown to promote apoptosis in non-small cell lung cancer cells. However, previous studies have not determined if baicalein exerts proapoptotic effects by modulating the metabolic pathways. ObjectiveTo investigate if baicalein induces apoptosis in lung cancer cells by modulating the glutamine-mTOR metabolic pathway. MethodsThe in vivo anti-lung cancer activity of baicalein (50, 100, and 200 mg/kg) was evaluated using a xenograft model. In vitro experiments were used to assess the efficacy of baicalein (for H1299: 12.5, 25, and 50 μM; for A549: 10, 20, and 40 μM) on lung cancer cell proliferation, colony formation, and apoptosis. Metabolomics analysis was performed using liquid chromatography-mass spectrometry. The binding of baicalein to glutamine transporters and glutaminase was examined using molecular docking. The overexpression of glutamine transporters was validated using qRT–PCR and western blot analyses. The levels of ASCT2, LAT1, GLS1, p-mTOR, mTOR, and apoptosis-related proteins were evaluated using western blot analysis. ResultsBaicalein inhibited lung cancer xenograft tumor growth in vivo and suppressed proliferation and promoted apoptosis in lung cancer cells in vitro. Additionally, baicalein altered amino acid metabolites, especially glutamine metabolites, in H1299 and A549 cells. Mechanistically, baicalein interacted with glutamine transporters as well as glutaminase and inhibited their activation. The expression of mTOR, an apoptosis-related protein and downstream target of glutamine metabolism, was also inhibited by baicalein treatment. Importantly, we next demonstrated the suppression of mTOR signaling and the induction of apoptosis by baicalein were achieved by regulating glutamine metabolism. ConclusionBaicalein inhibited the mTOR signaling pathway and induced apoptosis by downregulating glutamine metabolism. The potential of baicalein to induce apoptosis in lung cancer cells by selectively targeting the glutamine-mTOR pathway suggests an encouraging approach for treating lung cancer.

Anti-lung Cancer Activity of Synthesized Substituted 1,4-Benzothiazines: An Insight from Molecular Docking and Experimental Studies.

Thiazine, a 6-membered distinctive heterocyclic motif with sulfur and nitrogen atoms, is one of the heterocyclic compounds that functions as a core scaffold in a number of medicinally significant molecules. Small thiazine-based compounds may operate simultaneously on numerous therapeutic targets and by employing a variety of methods to halt the development, proliferation, and vasculature of cancer cells. We have, herein, reported a series of substituted 1,4 benzothiazines as potential anticancer agents for the treatment of lung cancer. In order to synthesize 2,3-disubstituted-1,4 benzothiazines in good yield, a facile green approach for the oxidative cycloaddition of 2-amino benzenethiol and 1,3-dicarbonyls employing a catalytic amount of ceric ammonium nitrate has been devised. All the molecules have been characterized by spectral analysis and tested for anticancer activity against the A-549 lung cancer cell line using various functional assays. Further in silico screening of compound 3c against six crucial inflammatory molecular targets, such as Il1-α (PDB ID: 5UC6), Il1- β (PDB ID: 6Y8I), Il6 (PDB ID: 1P9M), vimentin (PDB ID: 3TRT), COX-2 (PDB ID: 5KIR), Il8 (PDB ID: 5D14), and TNF-α (PDB ID: 2AZ5), was done using AutoDock tool. Among the synthesized compounds, propyl 3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazine-2- carboxylate (3c) was found to be most active based on cell viability assays using A-549 lung cancer cell line and was found to effectively downregulate various pro-inflammatory genes, like Il1-α, Il1-β, Il6, vimentin, COX-2, Il8, and TNF-α in vitro. The ability of the molecule to effectively suppress the proliferation and migration of lung cancer cells in vitro has been further demonstrated by the colony formation unit assay and wound healing assay. Molecular docking analysis showed the maximal binding affinity (- 7.54 kcal/mol) to be exhibited by compound 3c against IL8. A green unconventional route for the synthesis of 2,3-disubstituted-1,4 benzothiazines has been developed. All the molecules were screened for their activity against lung cancer and the data suggested that the presence of an additional unbranched alkyl group attached to the thiazine ring increased their activity. Also, in vitro and in silico modeling confirmed the anti-cancer efficiency of compound 3c, encouraging the exploration of such small molecules against cancer.

Statement of Retraction: Two new Bi(III) and Ce(III) chelates incorporating 1,10-phenanthroline-2,9-dicarboxylic acid: structure elucidation and anti-lung cancer activity study

Statement of Retraction: Two new Bi(III) and Ce(III) chelates incorporating 1,10-phenanthroline-2,9-dicarboxylic acid: structure elucidation and anti-lung cancer activity study

Activities of polysaccharide fractions from corn silk: Hemostatic, immune, and anti-lung cancer potentials

Corn silk is the stigma and style of corn and is rich in polysaccharides. Despite the extensive research on its polysaccharides, the hemostatic characteristics of effective parts and the related activities remain insufficiently explored. Corn silk polysaccharide (CSP) was extracted with hot water and purified using a diethylaminoethyl cellulose membrane. Then, it was separated with sephadex G-150 to obtain five fractions. These fractions were investigated for their potential in hemostasis, antioxidant, immune response, and anti-lung cancer activities. CSP-2, CSP-3, and CSP-4 significantly affected the coagulation indicators activated partial thromboplastin time (APTT) and thrombin time (TT) at 125–500 μg/mL. Corn silk flavonoids and saponins at 32.25 μg/mL significantly prolonged APTT, TT, and prothrombin time (PT). CSP-2, with potent antioxidant ability, approaches Vitamin C. At 25 μg/mL, CSPs nearly reached the phagocytosis of neutral red of lipopolysaccharides. The five fractions promoted the proliferation of RAW264.7 cells at 25–800 μg/mL and stimulated NO secretion at 25–100 μg/mL. CSP-2 also showed an 86 % inhibition rate effect on A549 at 200 μg/mL. These results indicate that CSP not only has hemostatic effects but also has immune and anti-lung cancer activities. Thus, it is a potential candidate compound with immune activity for managing bleeding in cancer.

Synthesis, characterization, anti-lung cancer activity, and in-silico studies of some novel triazole-based analogues as Pellizzari products

In the present research work, a series of novel (Z)-5-(cyclohexylidenehydrazono)-2-aryl-3H,5H-thiazolo[3,4-b][1,2,4]triazole derivatives were synthesized by Pellizzari reaction of (Z)-3-amino-2-(cyclo hexylidenehydrazono)thiazolidin-4-one with different aromatic amides. All the synthesized products were obtained in a good to excellent yields, and their structures were established based on UV-Vis, FT-IR, 1H NMR, 13C NMR, and HRMS analysis. To validate the experimental findings, in-silico studies of one synthesized compound (11a) were done with the help of density functional theory (DFT) at B3LYP/6-311++G(d,p) level. Frontier molecular orbitals, molecular electrostatic potential, and Reduced density gradient analysis were performed to better understand the electronic properties, and reactivity. Results of NLO, ELF, LOL, DOS, AIM, and vector analysis were reported. All the newly synthesized benzimidazole compounds had a cytotoxic impact, in some cases much more potent than the reference medication. The cytotoxicity of all the synthesized compounds were assessed against A549 cell lines using the MTT assay. Among them, compounds 11d and 11e showed more potent cytotoxicity having the IC50 value ∼90 and ∼80 µM, respectively. The molecular docking studies revealed an excellent affinity for the active sites of the matching gene regulation-inhibitor complex (BDR4) protein. Additionally, the evaluation of ADMET parameters indicated good pharmacokinetic properties of all the investigated compounds.

Assessment of Mononuclear/Dinuclear copper acylhydrazone complexes for lung cancer treatment

Non-platinum metal-based complexes have good potential for cancer treatment. Here, we designed and synthesized five hydrazone copper(II) complexes, [Cu2(HL)2Cl2] 1A, [Cu2(HL)2(NO3)H2O]·NO3 2A, [Cu2(HL)2Br2] 3A, [Cu(L)pyridine] 1B and [Cu(HL)(pyridine)Br] 3B, and evaluated their anti-lung cancer activities. MTT experiments revealed that these copper(II) complexes exhibit higher anticancer activity than cisplatin. Mechanism studies revealed that complex 3A induced G1 phase cell cycle arrest, and induced cell apoptosis via reactive oxygen species (ROS)-mediated mitochondrial dysfunction. Scratch wound healing assay was also performed, revealing that complex 3A have good anti-cell migration activity. Hemolysis assays showed good blood biocompatibility of complex 3A. Furthermore, complex 3A can significantly inhibit the proliferation of A549 3D tumor spheroid. An in vivo anticancer study showed that complex 3A could delays the growth of A549 tumor xenografts with lower systemic toxicity. These results highlight the great possibility of developing highly active copper complexes as anti-lung cancer agents.

Transcriptomics Reveals the Mechanism of Platycodin D Targeting TGFβ for Anti-Lung Cancer Activity.

Lung cancer is the most prevalent and lethal malignant tumor in China, primarily categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for more than 80% of all lung cancer cases, with current treatments primarily consisting of surgery, chemotherapy, and targeted therapy. However, these treatments often come with various adverse effects and drug resistance issues, highlighting the urgent need for new NSCLC therapies. Traditional Chinese medicine serves as a natural treasury of medicinal compounds and an important avenue for discovering novel active compounds. Platycodin D (PD) is a triterpenoid saponin isolated from the roots of Platycodon, possessing various pharmacological properties. Nevertheless, the exact mechanism of PD's anti-lung cancer activity remains unclear. In this study, 3 lung cancer cell models, A549, NCI-H1299, and PC-9, were employed. After intervention with Platycodin-D, tumor cell proliferation and migration were assessed. Cell migration ability was assessed through transwell assays, while transcriptomics was employed to explore the mechanism of PD's anticancer activity. Bioinformatic analysis revealed significant enrichment of apoptosis and the TGFβ pathway following PD intervention, as shown in gene expression heatmaps, where genes associated with cancer were significantly downregulated by PD intervention. Subsequently, we used immunofluorescent labeling of KI-67 to evaluate cell proliferation, flow cytometry to assess apoptosis, and Western blot to detect protein expression of TGFβ and P-SMAD3. Immunofluorescence was also employed to investigate E-cadherin, vimentin, and N-cadherin. Finally, molecular docking and dynamic simulations were utilized to study the interaction between PD and TGFβ proteins. The results of this study indicate that PD exhibits robust anti-lung cancer pharmacological activity, with its primary target being TGFβ. PD may serve as a potential TGFβ inhibitor and a candidate drug for NSCLC treatment.

Preparation, Characterization, and Anti-Lung Cancer Activity of Tetrandrine-Loaded Stealth Liposomes.

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, is a potential candidate for cancer chemotherapy. However, Tet has poor aqueous solubility and a short half-life, which limits its bioavailability and efficacy. Liposomes have been widely utilized to enhance the bioavailability and efficacy of drugs. In this study, Tet-loaded stealth liposomes (S-LPs@Tet) were prepared by ethanol injection method. Furthermore, physicochemical characterisation, biopharmaceutical behaviour, therapeutic efficacy, and biocompatibility of S-LPs@Tet were assessed. The prepared S-LPs@Tet had an average particle size of 65.57 ± 1.60 nm, a surface charge of -0.61 ± 0.10 mV, and an encapsulation efficiency of 87.20% ± 1.30%. The S-LPs@Tet released Tet in a sustained manner, and the results demonstrated that the formulation remained stable for one month. More importantly, S-LPs significantly enhanced the inhibitory ability of Tet on the proliferation and migration of lung cancer cells, and enabled Tet to escape phagocytosis by immune cells. Furthermore, in vivo studies confirmed the potential for long-circulation and potent tumor-suppressive effects of S-LPs@Tet. Moreover, ex vivo and in vivo safety experiments demonstrated that the carrier material S-LPs exhibited superior biocompatibility. Our research suggested that S-LPs@Tet has potential applications in lung cancer treatment.

Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide. The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases. Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf, but their mechanism of action has still not fully elucidated. We synthesized Moracin N (MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis. MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells. Chemical proteomic results showed that MAN targeted the programmed death ligand 1 (PD-L1) checkpoint pathway and T cell receptor (TCR) signaling pathway, indicating its immune-regulatory function. Cell-free surface plasmon resonance (SPR) results showed the direct interaction of MAN with PD-L1 protein. Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein. MAN downregulated the expression levels of PD-L1 in a time- and dose-dependent manner and disrupted the PD-L1/programmed death 1 (PD-1) binding, including other secondary metabolites of mulberry leaves Guangsangon E (GSE) and Chalcomoracin (CMR). Human peripheral blood mononuclear cells (PBMCs) co-cultured with MAN-treated A549 cells, resulting in the increase of CD8+ GZMB+ T cells and the decrease of CD8+ PD-1+ T cells. It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling. In vivo, MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis, indicating their synergistic effect. Taken together, secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling, enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer. Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.