Anti-lung Cancer Activity Research Articles

Selenium nanoparticles coated bacterial polysaccharide with potent antimicrobial and anti-lung cancer activities

Bacterial exopolysaccharides are homopolymeric or heteropolymeric polysaccharides with large molecular weights (10–1000 kDa). Exopolysaccharides' functional uses and potential have revolutionized the industrial and medicinal industries. Hence, the aim of the present study was to optimize the production of bacterial exopolysaccharide and apply it as a capping agent for selenium nanoparticles synthesis. Exopolysaccharide (EPS) producing Lactic acid bacteria (LAB) were isolated from dairy products then biochemically characterized and assessed for their potential antimicrobial effect. The most potent EPS producer was identified as Lactiplantibacillus plantarum strain A2 with accession number OP218384 using 16S rRNA sequencing. Overall, FTIR data of the extracted EPS revealed similarity with amylopectin spectrum. 1H NMR spectrum revealed an α-anomeric configuration of the glycosidic linkage pattern in the polysaccharides while the 13C NMR spectrum can also be separated into two main portions, the anomeric carbons region (δ 98–102 ppm) and the non-anomeric carbons region (δ 60–81 ppm). Antimicrobial activity of the produced EPS showed maximum activity against Staphylococcus aureus, MRSA, Enterobacter aerogenes, Klebsiella pneumoniae and Candida albicans respectively. The EPS capsule layer surrounding the bacterial cells was detected by TEM study. Optimization of EPS production was evaluated using Taguchi design, trial 23 reported the highest biomass yield and EPS output (6.5 and 27.12 g/L respectively) with 2.4 and 3.3 folds increase (from the basal media) respectively. The optimized exopolysaccharide was used as a capping and stabilizing agent for selenium nanoparticles (EPS-SeNPs) synthesis. Zeta potential, size and PDI of the synthesized nanoparticles were − 19.7 mV, 45–65 nm and 0.446 respectively with strong bactericidal and fungicidal effect against the tested pathogens. Complete microbial growth eradication was recorded after 6, 8 and 10 h against Staphylococcus aureus, Candida albicans and Klebsiella pneumoniae respectively. EPS-SeNPs showed a potent antioxidant effect reached 97.4% and anticancer effect against A549 lung cancer cell line (IC50 reached 5.324 µg/mL). EPS-SeNPs inhibited cancerous cell growth at S phase. Moreover, molecular studies revealed the anti-apoptotic activity of Bcl2's was inhibited and Bax was activated. The present investigation successfully synthesized selenium nanoparticles through bacterial EPS with significantly high antimicrobial and anticancer activity.

Characterization, Anti-lung Cancer Activity, and Cytotoxicity of Bio-synthesized Copper Nanoparticles by Thymus fedtschenkoi Leaf Extract

Characterization, Anti-lung Cancer Activity, and Cytotoxicity of Bio-synthesized Copper Nanoparticles by Thymus fedtschenkoi Leaf Extract

Assessment of antidiabetic, anti-inflammatory, antioxidant and anticancer activity competence of methonolic extracts of Trianthema ortulacastrum and Andrographis paniculata

An in-vitro investigation was performed to evaluate and compare the phytochemical, antioxidant, antidiabetic, anti-inflammatory, and anti-lung cancer activities of methanol extracts of aerial parts of Andrographis paniculata and Trianthema portulacastrum. Furthermore studied major functional groups of phytochemicals present in the methanol extracts of these plants through Fourier transform infrared (FTIR) analysis. The results showed that the methanol extract of A. paniculata contain more number of pharmaceutically valuable phytochemicals such as alkaloids, flavonoids, terpenoids, saponin, glycoside, phytosterol, and tannin than T. portulacastrum. Similar way the methanol extract of A. paniculata showed considerable dose dependent antioxidant (DPPH: 63%), antidiabetic (α-amylase: 82.31% and α-glucosidase inhibitions: 72.34%), and anti-inflammatory (albumin-denaturation inhibition: 76.3% and anti-lipoxygenase: 61.2%) activities (at 900 μg mL−1 concentration) than T. portulacastrum. However, the anti-lung cancer activities of these test plants against A549 cells were not considerable. According to FTIR analysis, the A. paniculata methanol extract has a larger number of characteristic peaks attributed to the active functional groups of pharmaceutically valuable bioactive components that belong to different types of phytochemicals. These findings imply that A. paniculata methanol extracts can be used for additional research, such as bioactive compound screening and purification, as well as assessing their potential biomedical uses in various in-vitro and in-research settings.

Prenylated chromones and flavonoids isolated from the roots of Flemingia macrophylla and their anti-lung cancer activity

BackgroundThe successful launch of icaritin, a therapeutic drug for liver cancer derived from Epimedium brevicornu, has provided new impetus for the development of prenylated flavonoids in the field of oncology. Flemingia macrophylla is reported to contain characteristic prenylated flavonoids which can regulate the p53 protein. We aimed to isolate these constituents and conduct activity evaluation, structure–activity relationship, and mechanism studies to provide candidate compounds for antitumor drug development.MethodsIn this study, chromatographic techniques combined with spectroscopic methods were used to separate, purify, and identify the constituents of Flemingia macrophylla methanol extract. The cytotoxic activity of the constituents was evaluated using an MTT assay with A549 and H1975 cells as the model. The binding mechanism between the compounds and the p53 protein was investigated with molecular docking and validated with cellular thermal shift assay (CETSA). Western blotting (WB) was employed to detect the expression of p53 protein and apoptosis-related proteins in cells.ResultsChiral HPLC separation of racemates 1 and 7 provided two pairs of undescribed enantiomers (1a/1b and 7a/7b), along with eight known compounds (2 − 9) isolated from Flemingia macrophylla roots. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of the enantiomers were determined from experimental and calculated electronic circular dichroism data. Compounds 1 − 7, and the non-prenyl analogues 10 − 13, were evaluated for cytotoxic activity against the human lung cancer A549 and H1975 cell line. Compounds 5 − 7 displayed better cytotoxicity than the positive control icaritin in A549 and H1975, with IC50 values ranging from 4.50 to 19.83 μmol·L-1 and < 5 μmol·L-1, respectively. The structure–activity relationships of the chromone or flavonoid analogues against A549 cells were discussed. Molecular docking results demonstrated that compound 7a has strong interaction with p53 and WB indicated that 7a induced apoptosis by increasing the p53 protein, decreasing the anti-apoptotic protein Bcl-2, and activating the caspase family in A549 cells. These results suggest that prenylated flavonoids are potential p53 protein activators.ConclusionThis study demonstrates that Flemingia macrophylla is rich in prenylated flavonoid constituents, among which compounds 5 and 7 exhibited significant cytotoxic activity against A549 cells and served as reference candidates for the design and development of prenylated compounds as antitumor therapeutic drugs.Graphical

Gigantol exerts anti-lung cancer activity by inducing ferroptosis via SLC7A11-GPX4 axis

Gigantol, a naturally occurring dibenzyl compound derived from various orchid species within the Dendrobium genus, exhibits notable pharmacological activity. We found that gigantol has significant anti-lung cancer properties, both in vitro and in vivo, which it exerts through the induction of ferroptosis. Furthermore, we found gigantol's specific interaction with the subunit solute carrier family 7 member 11 (SLC7A11) within the cystine/glutamate antiporter system (system Xc−), leading to the inhibition of glutathione (GSH) synthesis. This, in turn, disrupts redox homeostasis. Additionally, gigantol hinders the uptake of extracellular cystine via lung cancer cells, resulting in reduced cellular levels of cysteine, a vital precursor in GSH synthesis. This reduction, in turn, leads to an increase in the levels of glutamate. Simultaneously, our study reveals that the decrease in GSH significantly inhibits the activity of glutathione peroxidase 4 (GPX4), a key enzyme within the antioxidant system. Remarkably, N-acetylcysteine, a cystine precursor, effectively reverses gigantol-induced ferroptosis in lung cancer cells. This provides further confirmation that the anti-lung cancer mechanism of gigantol is to induce ferroptosis of lung cancer cells by targeting the SLC7A11-GPX4 signaling axis. In conclusion, our study underscores gigantol's potential as a promising candidate drug for the treatment of patients with lung cancer in clinical practice.

Phytosphingosine inhibits the growth of lung adenocarcinoma cells by inducing G2/M-phase arrest, apoptosis, and mitochondria-dependent pathway cell death in vitro and in vivo

In order to search for novel antitumor drugs with high efficiency and low toxicity, the anti-lung cancer activity of phytosphingosine was studied. Phytosphingosine is widely distributed in fungi, plants, animals, and has several biological activities, including anti-inflammation and anti-tumor. However, its anti-lung cancer activity needs to be further investigated. The effects and pharmacological mechanisms of phytosphingosine on lung cancer treatment were investigated both in vitro and in vivo. The results showed that phytosphingosine inhibited the growth of lung cancer cell lines. Phytosphingosine induced apoptosis through a mitochondria-mediated pathway, phytosphingosine arrested the cell cycle at the G2/M phase and induced apoptosis in a dose-dependent manner by increasing Bax/Bcl-2 ratio, which caused the decrease of mitochondrial membrane potential to promote the release of cytochrome C, caspase 9 and 3, and degrade PARP in A549 cells. The results showed that phytosphingosine could damage the mitochondrial functions, increase ROS levels, and arrest the cell cycle at the G2/M stages. Finally, phytosphingosine also inhibited the growth of tumor in mice. Taken together, phytosphingosine suppressed the growth of lung cancer cells both in vitro and in vivo and had potential application in the research and development of antitumor drugs. The aim of the present study was to explain the theoretical basis of phytosphingosine therapy for lung cancer and providing new possibilities for lung cancer treatment.

Angelica acutiloba Kitagawa flower induces A549 cell pyroptosis via the NF-κB/NLRP3 pathway for anti-lung cancer effects

Angelica acutiloba Kitagawa, a traditional medicinal herb of the Umbelliferae family, has been demonstrated to have anticancer activity. In this study, we investigated the anti-lung cancer effects of two compounds extracted from A. acutiloba flowers: kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE) and platanoside (PLA). MTT, cell colony formation, and cell migration (scratch) assays revealed that both KAE (100 μM) and PLA (50 μM and 100 μM) inhibited the viability, proliferation, and migration of A549 cells. Dichlorodihydrofluorescein diacetate assays showed that KAE and PLA also induced the generation of reactive oxygen species in A549 cells. Morphologically, A549 cells swelled and grew larger under treatment with KAE and PLA, with the most significant changes at 100 μM PLA. Fluorescence staining and measurement of lactate dehydrogenase release showed that the cells underwent pyroptosis with concomitant upregulation of interleukin (IL)-1β and IL-18. Furthermore, both KAE and PLA induced upregulation of NF-κB, PARP, NLRP3, ASC, cleaved-caspase-1, and GSDMD expression in A549 cells. Subsequent investigations unveiled that these compounds interact with NLRP3, augment NLRP3’s binding affinity with ASC, and stimulate the assembly of the inflammasome, thereby inducing pyroptosis. In conclusion, KAE and PLA, two active components of A. acutiloba flower extract, had significant anti-lung cancer activities exerted through regulation of proteins related to the NLRP3 inflammasome pathway.

An in-vitro evaluation of antifungal, anti-lungcancer (A549), and anti-hyperglycemic activities potential of Andrographis paniculata (Burm. f.) flower extract

The medical plant research has received more attention among researchers especially after the Covid-19 pandemic. This research performed to evaluate the antifungal, anti-lung cancer (A549), and anti-hyperglycemic activities of aqueous extract of Andrographis paniculata flower. Interestingly, A. paniculata flower aqueous extract contains pharmaceutically valuable phytochemicals such as alkaloid, phenolics, terpenoids, tannins, flavonoids, and protein. It also showed fine antifungal activity against test fungal pathogens in the following order as: Aspergillus niger > Fusarium solani > Trichoderma harzianum > A. parasiticus > P. expansum > Penicillium janthinellum with lowest MIC values as ranged from 100 to 300 μg mL−1. Interestingly, this aqueous extract also showed considerable anti-lung cancer activity, evidenced by dose and time dependent lung cancer cell line (A549) growth/proliferation inhibition/cytotoxicity activity (65%) at 300 μg mL−1 concentration. This can be achieved by plant extract through inducing the secretion of apoptosis related proteins such as TNF α, IFN-γ, and ınterleukin 2 leads to apoptosis in A549 cells. It also showed fine anti-diabetic activity by inhibiting α -amylase (58.41%) than α-glucosidase (54.74%) at 200 μg mL−1 concentration. The UV as well as FTIR results demonstrated that the aqueous extract of A. paniculata flower contains pharmaceutically valuable bioactive compounds, which may be responsible for the wide range of biomedical applications.

Synthesis of Bio-Active Silver Nanoparticles against Human Lung Cancer Cell Line (A549) with Little Toxicity to Normal Cell Line (WRL68).

Nanomaterials are characterized by mechanical, thermal, chemical, biological, and other properties that are different from the basic materials that make them up due to their large surface area to size ratio and quantum effect. There are multiple ways to produce nanomaterials mechanically, chemically, and physically, but they are not safe for the environment. Researchers have sought to find safe methods for the production of nanomaterials, such as green manufacturing, that is, manufacturing nanomaterials from plants. Moreover, there are other sources, such as bacteria or fungi that are used in the production of nanomaterials. This study aimed to try to find an alternative to chemically manufactured drugs, such as those used in the treatment of human cancers, through nanotechnology and from plant sources (green-biosynthesis), which is characterized by abundance and low economic cost. Silver nanoparticles were green-synthesized using an aqueous extract of the licorice plant, their properties were diagnosed, and their differences with the crude aqueous extract were determined. The sizes of nanoparticles were within the range of 60.27-89.80 nm, while the sizes of the crude aqueous extract particles were within the range of 53.96-113.1 nm. Atomic force microscopy was used to find out the shapes, topography, roughness, and protrusions of the surfaces of biosynthesized AgNPs and aqueous extract particles, where the roughness rate of the nanoparticles was 75.54 nm, while it appeared. In vitro test of AgNPs showed a higher anti-lung cancer activity against the A549 cell line than that of the extract at an inhibitory concentration for half of the cells used in the experiment (IC50) of 58.78 µg/ml while the IC50 of the extract was 67.44 µg/ml. The results showed that the toxicity of AgNPs on the normal hepatocyte line (WRL68) was less than that of the aqueous extract, with IC50 concentrations of 244.2 and 147.0 µg/ml, respectively. It is worth mentioning that the lower IC50 led to higher toxicity.

Novel green synthesis of zinc oxide nanoparticles using Salvia rosmarinus extract for treatment of human lung cancer

Abstract A green and low-cost approach was run to synthesize zinc nanoparticles (NPs) using rosemary extract. The NPs were identified by various methods, i.e., ultraviolet-visible and Fourier transform infrared spectroscopy, FE-scanning electron microscope imaging, X-ray diffraction, and energy-dispersive X-ray analysis. The radical scavenging activity and MTT assays were used to evaluate the biological activity of ZnO-NPs@Rosemary. The results revealed a spherical shape for ZnO-NPs@Rosemary with a crystal size of 30.74 nm. ZnO-NPs@Rosemary could scavenge the free radicals of DPPH with an IC50 of 87.62 ± 0.47 μg/mL. An MTT assay was run to investigate the anti-cancer activity of ZnO-NPs@Rosemary against PC-14, LC-2/ad, and HLC-1 as the selected lung cancer cell lines. The highest sensitivity of NPs was found against PC-14 with IC50 of 178.84 ± 2.13. A dose-dependent activity was observed for ZnO-NPs@Rosemary against the chosen cell lines. The outcomes of the present study revealed an acceptable anti-lung cancer activity of ZnO-NPs@Rosemary.

Advanced culture strategy shows varying bioactivities of sulfated polysaccharides of Poria cocos

This study compares the bioactivity of six sulfated polysaccharides derived from glucose- and sucrose-feeding extracted from P. cocos. Anti-inflammatory potentials of these polysaccharides were evaluated by pretreating lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Of the tested polysaccharides, the sulfated polysaccharide derived from sucrose-feeding at the concentration of 40 g/l (referred to as “suc 40”) exhibited the highest anti-inflammatory activity, of 83 %, and 33 % inhibition of IL-6 and TNF-α secretion, respetively. It achieved this by inhibiting the p-38 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways. On the other hand, the sulfated polysaccharide derived from glucose-feeding at a concentration of 20 g/l (referred to as “glc 20”) demonstrated the greatest anti-lung cancer activity. This was achieved by inducing apoptotic-related molecules, such as poly (ADP-ribose) polymerase (PARP) and CHOP. Furthermore, glc 20 had the highest contents of sulfate, fucose, and mannose compared to the other tested polysaccharides. This suggests that the composition of monosaccharide residues are critical factors influencing the anti-inflammatory and anti-cancer activities of these sulfated polysaccharides. Overall, this study highlights the potential of sulfated polysaccharides derived from P. cocos to function as bioactive compounds with anti-inflammatory and anti-cancer properties.

Potential targets of natural medicines: preventing lung cancer pre-metastatic niche formation by regulating exosomes.

Lung cancer is one of the most devastating diseases worldwide with high incidence and mortality, and the incidence continues to rise. Metastasis is the leading cause of death in lung cancer patients, yet the molecular effectors underlying tumor dissemination remain poorly defined. Research findings in recent years confirmed primed microenvironment of future metastatic sites, called the pre-metastatic niche, is a prerequisite for overt metastasis. Exosomes have recently emerged as important players in pre-metastatic niche formation. Natural medicines have traditionally been rich sources of drug discovery. Some of them exhibit favorable anti-lung cancer activity. The review focused on the latest advances in the regulation of the pre-metastatic niche formation in lung cancer by the contents of exosomes of representative natural medicines. Additionally, the mechanism of natural medicines was summarized in detail, which would provide new insights for anti-cancer new drug development.

Synthesis, in-Silico investigations, molecular docking, ADMET, and anti-lung cancer activity studies of 1,2,4,5-tetraazaspiro[5.5]undecane-3-thione

Several innovative materials' properties are predicted using in silicon investigations, a computer simulation technique. 1,2,4,5-tetraazaspiro[5.5]undecane-3-thione was synthesized and characterized by using a variety of spectroscopic approaches followed by in silicon studies. DFT at the B3LYP functional level and the basis set 6–311 ++G (d,p) was used. The title molecule was investigated for its electric dipole moment, polarizability, andstatic hyperpolarizability. In silicon studies of the compound were done and showed good result to predict pharmacokinetics, lipophilicity, physicochemical and medicinal properties of the target molecule. Molecular docking was done between receptors and ligand by simulating molecular interactions in BRD4 proteins. The compound was also bio-evaluated for its anti-lung cancer activity against A549 cancer cell line. Theoretical calculation of ADMET properties suggested that the synthesized compound shows good pharmacokinetic profile. The results of cytotoxic evaluation indicated that the compound has broad-spectrum cytotoxic activity with IC50 values of 300 μM against A549 cell line.

Statement of Retraction: Construction of two coordination polymers based on imidazolyl and aromatic dicarboxylic acid ligands: structural diversity and anti-lung cancer activity study

Statement of Retraction: Construction of two coordination polymers based on imidazolyl and aromatic dicarboxylic acid ligands: structural diversity and anti-lung cancer activity study

Statement of Retraction: Structural diversity and anti-lung cancer activity evaluation of two Co(II) and Cu(II) containing mixed-ligand coordination polymers

Statement of Retraction: Structural diversity and anti-lung cancer activity evaluation of two Co(II) and Cu(II) containing mixed-ligand coordination polymers

Screening of anti-cancer compounds from Vaccariae Semen by lung cancer A549 cell fishing and UHPLC-LTQ Orbitrap MS

Vaccariae Semen, derived from the dried ripe seed of Vaccaria segetalis (Neck.) Garcke, has various therapeutic characteristics in traditional Chinese medicine (TCM), containing promoting blood circulation and unblocking meridians. It exhibits significant anti-cancer activity and is therapeutically utilized to treat and reduce chemotherapy adverse effects in cancer patients, notably those with lung cancer. However, the active ingredients responsible for its anti-lung cancer efficacy remain unknown. In this study, we used A549 cell fishing in conjunction with UHPLC-LTQ Orbitrap MS to screen for anti-lung cancer active components in Vaccariae Semen. The cell counting Kit-8 (CCK-8) assay revealed that the n-butanol extract substantially reduced A549 cell growth. Through the cell fishing assay, we found 14 A549 cell-binding compounds in the n-butanol extract, all of which were identified as triterpenoid saponins. The total saponins of Vaccariae Semen were subsequently purified using macroporous adsorption resin (MAR), and they showed a significant inhibitory effect on the proliferation of A549 lung cancer cells, as well as alterations in cell morphology, apoptosis, and fragmentation. In conclusion, saponins were discovered as the key active components responsible for the anti-lung cancer activity of Vaccariae Semen.

CT2-3 induces cell cycle arrest and apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through regulating PI3K/AKT pathway

Rheumatoid arthritis (RA) is a kind of chronic autoimmune disease. The existing therapies encountered several challenges. Therefore, continued novel anti-RA drug discovery remains necessary for RA therapy. Recently, our group reported a novel compound named CT2-3, which could be realized as a hybrid of the natural product magnolol and phthalimide and exhibited anti-lung cancer activity. However, the effect of CT2-3 on RA is unclear. Here, we aim to explore the effect and potential mechanism of CT2-3 on the abnormal functions of RA-fibroblast-like synoviocytes (RA-FLSs). In this study, we identified the important role of the dysregulated cell cycle and apoptosis of RA-FLSs in RA progression. Interestingly, we found that CT2-3 inhibited the proliferation and DNA replication of primary RA-FLSs and immortalized RA-FLSs namely MH7A. In addition, CT2-3 downregulated the mRNA and protein expression of cyclin-dependent kinase 2 (CDK2), cyclin A2, and cyclin B1, resulting in cell cycle arrest of primary RA-FLSs and MH7A cells. Also, CT2-3 downregulated the level of B-cell lymphoma-2 (Bcl-2), and increased the level of Bcl-2 associated X (Bax), contributing to apoptosis of primary RA-FLSs and MH7A cells. Furthermore, differential analyses of RNA-sequencing, Western blot, and network pharmacological analysis confirmed that CT2-3 inhibited phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway of primary RA-FLSs and MH7A cells. In conclusion, CT2-3 induces cell cycle arrest and apoptosis in RA-FLSs through modulating PI3K/AKT pathway, which may serve as a potential lead compound for further novel small molecule anti-RA drug development.

Elemene induces cell apoptosis via inhibiting glutathione synthesis in lung adenocarcinoma.

The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with β-elemene (BE) being its main active compound, along with trace amounts of β-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation. In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines. The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC50) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24h. Non-targeted metabolomics analysis was performed on A549cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis. Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC50 of EE and its main active components, BE and BC, was around 60μg/mL. Flow cytometry analysis showed that BE and BC blocked the G2/M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated. EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis.

Ebracteolatain A Inhibits Lung Cancer Growth via p21 and p27 Mediated Cell-Cycle Arrest

Objective: Lung cancer is a refractory tumor with a poor five-year survival rate. Ebracteolatain A (EA), a key acetyl-phloroglucinol derived from the traditional Chinese herb Langdu, has been reported to have anti-tumor activity in human breast cancer. However, the therapeutic efficacy and underlying mechanism of lung cancer remain to be elucidated. In the present study, we intended to evaluate whether EA exhibits anti-lung cancer activity and elucidate the underlying mechanisms. Methods: ATPlite and clonogenic survival assays were used to assess the inhibiting effect of EA on two lung cancer cell lines in vitro. FACS was conducted to determine the cell-cycle profiling of lung cancer cells upon treatment with EA. Western blot was performed to detect the level of related proteins in EA-treated lung cancer cells. RNA silencing and other experiments were used to identify the molecular mechanism of EA-triggered cell-cycle arrest. Furthermore, a xenograft tumor model was constructed to evaluate the therapeutic effect and potential mechanism of EA in vivo in mice. Results: EA significantly inhibited the growth of lung cancer cells both in vitro and in vivo. Mechanistically, EA-induced G1 phase cell-cycle arrest is mediated by the accumulation of p21 and p27. Conclusion: Our findings revealed the anti-lung cancer effect of EA and the mechanisms, providing a solid scientific basis for EA as an attractive choice for lung cancer therapy.

Preparation and Anti-Lung Cancer Activity Analysis of Guaiacyl-Type Dehydrogenation Polymer.

In this paper, guaiacyl dehydrogenated lignin polymer (G-DHP) was synthesized using coniferin as a substrate in the presence of β-glucosidase and laccase. Carbon-13 nuclear magnetic resonance (13C-NMR) determination revealed that the structure of G-DHP was relatively similar to that of ginkgo milled wood lignin (MWL), with both containing β-O-4, β-5, β-1, β-β, and 5-5 substructures. G-DHP fractions with different molecular weights were obtained by classification with different polar solvents. The bioactivity assay indicated that the ether-soluble fraction (DC2) showed the strongest inhibition of A549 lung cancer cells, with an IC50 of 181.46 ± 28.01 μg/mL. The DC2 fraction was further purified using medium-pressure liquid chromatography. Anti-cancer analysis revealed that the D4 and D5 compounds from DC2 had better anti-tumor activity, with IC50 values of 61.54 ± 17.10 μg/mL and 28.61 ± 8.52 μg/mL, respectively. Heating electrospray ionization tandem mass spectrometry (HESI-MS) results showed that both the D4 and D5 were β-5-linked dimers of coniferyl aldehyde, and the 13C-NMR and 1H-NMR analyses confirmed the structure of the D5. Together, these results indicate that the presence of an aldehyde group on the side chain of the phenylpropane unit of G-DHP enhances its anticancer activity.