A549 Lung Cancer Research Articles

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

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

Juglone triggers apoptosis of non-small cell lung cancer through the reactive oxygen species -mediated PI3K/Akt pathway.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally occurring naphthoquinone in J. mandshurica, exhibits significant cytotoxic activity against various cancer cell lines. However, whether the anticancer activity of juglone is associated with oxidative stress remains unexplored. In this study, mouse Lewis lung cancer (LLC) and human non-small cell lung cancer A549 cells were used to explore the anticancer mechanisms of juglone. Juglone inhibited LLC and A549 cells viability, with IC50 values of 10.78 μM and 9.47 μM, respectively, for 24 h, and substantially suppressed the migration and invasion of these two lung cancer cells. Additionally, juglone arrested the cell cycle, induced apoptosis, increased the cleavage of caspase 3 and the protein expression of Bax and Cyt c, and decreased the protein expression of Bcl-2 and caspase-3. Furthermore, juglone treatment considerably increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, but suppressed glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD) activities. It also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which was attenuated by 1,3-diCQA (an activator of PI3K/Akt). Moreover, N-acetylcysteine (a ROS scavenger) partially reversed the positive effects of juglone in terms of migration, invasion, ROS production, apoptosis, and PI3K/Akt pathway-associated protein expression. Finally, in tumor-bearing nude mouse models, juglone inhibited tumor growth without any apparent toxicity and significantly induced apoptosis in NSCLC cells. Collectively, our findings suggest that juglone triggers apoptosis via the ROS-mediated PI3K/Akt pathway. Therefore, juglone may serve as a potential therapeutic agent for the treatment of NSCLC.

Synergistic Inhibitory Effect of Gliquidone Against Cisplatin‐Resistant Human Lung Adenocarcinoma

Cisplatin (CDDP) can combat various types of cancers, employing a multifaceted approach against these malignant diseases. Despite its efficacy, resistance to CDDP remains a significant clinical challenge, often resulting in treatment failure and disease progression. Currently, efforts are underway to unravel the mechanisms of CDDP drug resistance in cancer treatment. The elevated presence of glutathione S‐transferase pi‐1 (GSTP1‐1) within tumor cells plays a pivotal role in the development of resistance toward the effects of CDDP. GSTP1‐1 contributes to detoxification by conjugating glutathione (GSH) to CDDP, reducing its accumulation and effectiveness in the tumor cells. In this study, the efficacy of gliquidone, an antidiabetic drug, demonstrated its capacity to impede tumor cell proliferation in both lung cancer A549 cell lines and A549/CDDP cell lines. This was achieved by suppressing the expression of GSTP1‐1 within tumor cells (IC50: 16.8 ± 0.8 μM). Furthermore, through the establishment of a nude mouse model featuring lung adenocarcinoma A549/CDDP cell transplantation tumors, gliquidone demonstrated a significant therapeutic effect on the mice tumors, while avoiding discernible side effects. These findings suggest that gliquidone could potentially be repurposed as an adjunct therapy in CDDP‐resistant lung cancer.

Polyhydroxy Sterols Isolated From Ganoderma sinense Spores and Their Cytotoxic Activities

Background: The fruiting body of Ganoderma sinense Zhao, Xu et Zhang iscertified as an authoritative medical material in the Chinese Pharmacopoeia 2020 edition and has been used as a crude drug for a long time. G sinense spores are crucial part of the fruiting body of G sinense and exhibited antitumor and immune-enhancing activities according to our previous reports. However, there were few studies about the chemical composition of G sinense spores. This study was aimed at the structure determination and antitumor effect of the sterols isolated from G sinense spores. Methods: Modern chromatographic methods were applied to isolate compounds from the ruptured spores of G sinense. Their chemical structures were elucidated by analyses of one-dimensional and two-dimensional 1H nuclear magnetic resonance, and high-resolution electrospray ionization mass spectrometry data. The cytotoxicities of the isolated compounds against 3 tumor cell lines, human non-small cell lung cancer A549 and 95D cells, and human hepatocellular carcinoma HepG2 cells were measured by Cell Counting Kit-8. Results: A novel ergosterol derivative, (22 E,24 R)-3β,5β,6α,7α,14β-pentahydroxyergosta-8,22-dien-15-one (1), and 5 known sterols, (22 E,24 R)-3β,5α,9α,14β-tetrahydroxyergosta-7,22-dien-6-one (2), (22 E,24 R)-ergosta-7,9(11),22-triene-3β,5α,6β-triol (3), (22 E,24 R)-ergosta-7,9(11),22-triene-3β,5α,6β,14α-tetrol (4), β-daucosterine (5), and (22 E,24 R)-ergosta-7,22-diene-3β,5α,6β,9α-tetrol (6), were obtained from the ruptured spores of G sinense. Compound 1 exhibited cytotoxicity against A549 cells and HepG-2 cells with IC50 values of 65.12 ± 4.76 and 97.34 ± 6.36 μM, respectively. Compounds 1, 2, and 4 were obtained from G sinense for the first time. Conclusion: This paper is a continuation of an investigation of the chemical ingredients from G sinense spores and their antitumor effect. Only compound 1 showed weak cytotoxicities against A549 cells and HepG-2 cells.

The cytotoxic activity of lignans and monoterpenoids from the male carica papaya flowers on A549 lung cancer, Hep3B liver cancer, and MCF-7 breast cancer cell lines

Two lignans (lariciresinol (1) and dehydrodiconiferyl alcohol (2)), and four monoterpenoids (vitexoid (3), 6-hydroxy-2,6-dimethyl-2,7-octadienoic acid (4), 6-hydroxy-2,6-dimethyloct-7-enoic acid (5), 2,6-dimethylocta-2,7-diene-1,6-diol (6)) from the male Carica papaya flowers are conducted a cytotoxic activity for lung cancer cells (A549), liver cancer cells (Hep3B), and breast cancer cells (MCF-7). The results, lignan (1), and monoterpenoid (3), (6) exhibited medium cytotoxic activity on these cancer cells with IC50 from 34.73±1.55 to 66.12±5.60 µg/mL. Lignan (2) displayed medium cytotoxic activity on MCF-7, Hep3B with IC50 60.85±4.43, 62.32±5.03 µg/mL, respectively, and weak cytotoxic activity on A549 with IC50 70.99±7.26 µg/mL. Monoterpenoids (4), and (5) showed medium cytotoxic activity on MCF-7 with IC50 54.15±5.89, 67.49±2.41 µg/mL, respectively, and weak cytotoxic activity on A549, and Hep3B with IC50 from 72.25±3.13 to 86.03±7.57 µg/mL. Ellipticine was a positive control.

Structural optimization of a lysine demethylase 5 inhibitor for improvement of its cellular activity

Lysine demethylase 5 (KDM5) subfamily proteins are important in epigenetic gene regulation. They are involved in the growth and drug resistance of cancer cells. Therefore, KDM5s are potential cancer therapeutic targets, and their inhibitors hold promise as anti-cancer drugs. Several KDM5 inhibitors, including KDM5-C49 (2a), have exhibited potent KDM5-inhibitory activities in in vitro enzyme assays. However, they do not show enough cellular activity despite being converted to their prodrugs. We hypothesized that their poor lipophilicity should prevent them from sufficiently penetrating the cell membrane, and introducing more lipophilic groups should improve cellular activities. In this study, we investigated 2a and KDM5-C70 (3a), a prodrug of 2a, and attempted to improve its cellular activity by replacing the N,N-dimethyl amino group of 3a with more lipophilic groups. N-Butyl, N-methyl amino compound 2e exhibited potent and selective KDM5-inhibitory activity equal to that of 2a. Furthermore, the cell membrane permeability of 3e, an ethyl ester prodrug of 2e, was six times higher than that of 3a in a parallel artificial membrane permeation assay. In addition, western blot analysis indicated that treating human lung cancer A549 cells with 3e increased histone methylation levels more strongly than that with 3a. Thus, we identified compound 3e as a more cell-active KDM5 inhibitor that has sufficient cell membrane permeability.

Biowastes-derived enzyme-powered zinc oxide and titanium oxide nanomaterials synthesis for anticancer and eco-friendly photocatalytic activity

Biowastes derived enzyme powered zinc oxide (ZnO) and titanium oxide (TiO2) nanomaterials were prepared using a soft-chemical method and their photocatalytic dye degradation efficiencies against toxic Methylene Blue (MB - cationic) and Methyl Orange (MO-anionic) dyes were studied. The enzymes prevalent in certain biowastes (vegetable wastes and fruit peels) are derived through eco-friendly fermentation process and used for nanomaterial synthesis. The enzyme quantitative assay confirmed the presence of the enzymes viz., protease, peroxidase, cellulase, amylase and lipase in the synthesized nanopowders. The photocatalytic results showed the enhanced combined effect of the semiconductor photocatalyst (ZnO and TiO2) and the bio-catalyst (enzymes). The efficiency of the resultant photocatalysts: ZnO - 95% (60 min) and TiO2 99% (60 min). The XRD results confirm the crystallized form of enzymes in the nanomaterial. The desirable morphological changes caused by the enzyme coupling with semiconductor was evidenced from SEM images. The study showed that the synthesized material (enzyme powered ZnO and TiO2) are desirable candidates for environmentally friendly, biocompatible photocatalysis for toxic dyes degradation. The cytotoxicity studies revealed that the material may effectively destroy the lung cancer A-549 cells. The half maximal inhibitory concentration (IC50) values of enzyme powered ZnO and TiO2 are 51.75 ± 0.05 μg/mL and 52.25 ± 0.05 μg/mL, respectively. Thus, the biowastes derived enzyme powered ZnO and TiO2 can be considered as promising materials for cost-effective dye degradation and anticancer activities.

Preparation, characterization, and anticancer effects of an inclusion complex of coixol with β-cyclodextrin polymers

Context Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. Objective This study prepared a water-soluble coixol-β-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. Materials and methods The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. Results The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. Discussion and conclusions These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

Proteomic analysis reveals the molecular mechanism of Astragaloside in the treatment of non-small cell lung cancer by inducing apoptosis

BackgroundAstragaloside III (AS III), a saponin-like metabolite derived from the traditional Chinese medicine Astragali Radix, has been shown to be effective in the treatment of cancer and heart failure, and a variety of digestive disorders. However, its molecular mechanism in the treatment of non-small cell lung cancer (NSCLC) is unknown.MethodsHuman lung cancer A549 cells and NCI-H460 cells and a normal human lung epithelial cell BEAS-2B were treated with different concentrations of AS III. CCK-8 and EdU staining were used to determine the anti-proliferative effects of AS III in vitro. Quantitative proteomic analysis was performed on A549 cells treated with the indicated concentrations of AS III, and the expression levels of apoptosis-related proteins were examined by Western blotting.ResultsAS III treatment significantly inhibited proliferation and increased apoptosis in A549 and H460 cells and modulated functional signaling pathways associated with apoptosis and metabolism. At the molecular level, AS III promoted a reduction in the expression of ANXA1 (p < 0.01), with increased levels of cleaved Caspase 3 and PARP 1. In addition, AS III treatment significantly decreased the LC3-I/LC3-II ratio. The results of experiment in vitro showed that AS III promoted NSCLC apoptosis by down-regulating the phosphorylation levels of P38, JNK, and AKT (p < 0.01), inhibiting the expression of Bcl-2 (p < 0.01), and up-regulating the expression of Bax (p < 0.01).ConclusionThese findings provide a mechanism whereby AS III treatment induces apoptosis in NSCLC cells, which may be achieved in part via modulation of the P38, ERK and mTOR signaling pathways.

Cytotoxic depsidones and xanthones from Garcinia esculenta Y. H. Li

Six new compounds, including two depsidones garciculendepsidones A and B (1 and 2), one prenylated xanthone garciculenxanthone (3) and three dimeric xanthones bigarciculenxanthones A–C (4–6), were isolated from the twigs and leaves of Garcinia esculenta Y. H. Li. Their structures were elucidated based on comprehensive analyses of spectral data, including HRESIMS, 1D and 2D NMR, and ECD calculation. All the isolates were tested for their cytotoxicity against five human cancer cell lines (myeloid leukemia HL-60, lung cancer A-549 cells, hepatocellular carcinoma SMMC-7721, breast cancer MDA-MB-231 and colon cancer SW480), among them, compounds 3–5 displayed cytotoxic potential, especially garciculenxanthone (3) had the lowest IC50 value of 8.2 μm for lung cancer A-549 cells.

Ecofriendly bio-synthesis and spectral characterization of copper nanoparticles using fruit extract of Pedalium murex L.: in vitro evaluation of antimicrobial, antioxidant and anticancer activities on human lung cancer A549 cell line

ABSTRACT The usage of copper nanoparticles (CuNPs) is now acknowledged as a promising therapeutic agent in the detection and treatment of cancer. This study aimed to develop a sustainable method for synthesizing CuNPs using Pedalium murex L. and characterization by SEM, FTIR, XRD & UV-Vis methods. The produced CuNPs were primarily spherical and varied in shape, and the average dimension ranged between 20 and 50 nm. The aqueous fruit juice of Pedalium murex L. contained biomolecules that serve as capping and reducing agents for the production of CuNPs, according to the findings of FTIR analysis. Various assays were used to determine the fruit extract’s in vitro antioxidant activity. CuNPs exhibited dose-dependent cytotoxicity and apoptosis promotion in A549 cells. The findings demonstrated that biosynthesized CuNPs using Pedalium murex L. fruit juice have anti-cancer properties and can be used in lung cancer treatment, particularly for early-stage intervention.

Synthesis and biological evaluation of novel bi-gold mitocans in lung cancer cells.

Mitochondria are promising drug target for cancer treatment. We previously demonstrated that a bi-gold compound BGC2a was more potent than the mono-gold drug auranofin in suppressing cancer cells due to increased gold atom number that led to higher drug accumulation in and thereby inhibition of mitochondria. To exploit the potential of this new strategy, we further designed and synthesized a series of bi-gold mitocans, the compounds targeting mitochondria. The results showed that most of the newly synthesized mitocans exhibited obviously lower IC50 than auranofin, an old drug that is repurposed in clinical trials for cancer treatment. The best mitocan C3P4 was nearly 2-fold more potent than BGC2a in human non-small cell lung cancer A549 cells and mantle cell lymphoma Jeko-1 cells, exhibiting substantial colony formation-suppressing and tumor-suppressing effects in A549 cells xenograft model. C3P4 induced apoptosis in a dose-dependent manner and arrested cell cycle at G0/G1 phase. The mechanistic study showed that C3P4 significantly increased the global reactive oxygen species and mitochondrial superoxide level, and reduced the mitochondrial membrane potential. C3P4 preferentially accumulated in mitochondria as measured by the gold content and substantially inhibited oxygen consumption rate and ATP production. These results further validated our hypothesis that targeting mitochondria would be promising to develop more potent anticancer agents. C3P4 may be further evaluated as a drug candidate for lung cancer treatment.

Effect of biofilm formation and cytotoxicity of biogenic silver nanoparticles (AgNPs) synthesized from a medicinal plant Sterculia foetida L.

The biogenic synthesis of silver nanoparticles mediated by medicinal plant Sterculia foetida was the prime experimental analysis of present study. The most important aim and focus of this study was to synthesis the AgNPs via biological method and the same had been evaluated against bio-film formation and dose dependent cyto-toxicity against cancer cells. This in vitro comprehensive analysis show that Ag had more advantage than other metals, the NPs was mediated by plant residue. And the NPs were further characterized by UV showing the sharp absorption peak at 455 nm; the identification of corresponding functional section proved by the parameter like FTIR, where conversion of Ag ions and capping agent is determined, the analysis on X- ray diffraction demonstrate the AgNPs found to be crystalline nature and face-centered like cubic structure. FESEM cum EDAX has showed the surface morphology with 40-50nm. After the physiochemical characterization, the AgNPs were evaluated with biofilm formation and cancer cells. In cyto-toxic study, two cell lines such as MCF 7 lung cancer cell line and A549 Breast cancer cell line were experimented and the values are AgNPs (IC50 =11.50± 0.05 µg and IC50 = 5.5± 0.05 µg/mL); AgNO3- (IC50 = 5.8± 0.05 µg and IC50 = 6.5± 0.05µg/mL) and Sterculia foetida (IC50 &gt; 5000 µg/mL and IC50 &lt; 5000 µg/mL). Another application of this present study is anti-biofilm assay. The selected bacterial strains are methicillinresistant Staphylococcus aureus; PA 14-Pseudomonas aeruginosa and Vibrio cholerae. Hence, the findings recommend that silver nanoparticles from medicinal plant Sterculia foetida is effective and can be used against bacteria and more precisely for cancer cell study.

Investigation of the mechanism of huangqi and danggui decoction in treating non-small-cell lung cancer based on network pharmacology

Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases, which is a leading cause of cancer mortality worldwide. While therapies such as chemotherapy, radiation, immunotherapy and targeted drugs have shown efficacy, resistance remains a major obstacle. Traditional Chinese medicine (TCM) offers a multi-target approach that may help overcome resistance. This study analyzed the active ingredients of Huangqi and Danggui decoction (HQDGD), a classic TCM formula, and their effects on NSCLC using network pharmacology and experimental validation. Active compounds were identified from TCM databases and linked to gene targets using prediction tools and were compared to NSCLC-related genes to find shared targets. Protein-protein interaction network analysis and pathway enrichment analysis were used to find HQDGDs pharmacology and experiments on lung cancer A549 cells validated that key HQDGD compounds curcumin, quercetin and -angelicalactone inhibited proliferation and migration, suppressed JAK2/STAT3 activation, and downregulated downstream HIF1A and VEGF. The multi-target actions of HQDGD may overcome resistance in NSCLC. Our integrated computational and experimental approach elucidated the compound-target-pathway mechanisms of a TCM formula against NSCLC, supporting future drug development and research.

Eleutheroside B induces apoptosis and autophagy of lung cancer cells by regulating PI3K/Akt/mTOR pathway

This study investigated the effect of eleutheroside B on apoptosis and autophagy of lung cancer A549 and H460 cells and its molecular mechanism. MTT assay was used to detect the cytotoxicity of eleutheroside B at 5, 10, 15, 20, 25, 30, 35, 40, and 45 mmol·L~(-1) on lung cancer cells. Trypan blue exclusion assay was used to detect the effect of eleutheroside B on the survival rate of lung cancer A549 and H460 cells at different time. Colony formation assay was used to detect the effect of eleutheroside B on the proliferation of lung cancer A549 and H460 cells. AO/EB fluorescence double staining and Hoechst 33342 fluorescence staining were used to detect the effect of eleutheroside B on apoptosis of lung cancer A549 and H460 cells, and Western blot was used to detect apoptosis-related proteins to explore the apoptosis-related molecular mechanism. AO fluorescence staining and Western blot were used to detect the expression of autophagic vesicles and autophagy-related proteins P62 and LC3. The results showed that compared with the control group, eleutheroside B inhibited the growth of lung cancer A549 and H460 cells in a concentration-dependent manner. The optimal effect time of eleutheroside B on lung cancer A549 and H460 cells was 24 h, and the optimal concentrations were 28.64 and 22.16 mmol·L~(-1), respectively. Eleutheroside B could inhibit the colony formation of A549 and H460 cells. Compared with the control group, eleutheroside B could promote the formation of apoptotic bodies and induce cell apoptosis, as well as induce the expression of mitochondrial pathway-related proteins. Under the effect of eleutheroside B, the acidic autophagy vacuole in lung cancer cells increased, LC3Ⅱ expression increased, P62 protein expression decreased, and PI3K, p-Akt, and p-mTOR protein expression decreased in the PI3K/Akt/mTOR pathway. Studies have shown that eleutheroside B can inhibit the growth of lung cancer cells, reduce colony formation, induce apoptosis of lung cancer cells through mitochondrial pathway, and induce autophagy. The mechanism may be related to the PI3K/Akt/mTOR pathway.

Simplified Synthesis of Renieramycin T Derivatives to Target Cancer Stem Cells via β-Catenin Proteasomal Degradation in Human Lung Cancer.

Cancer stem cells (CSCs) found within cancer tissue play a pivotal role in its resistance to therapy and its potential to metastasize, contributing to elevated mortality rates among patients. Significant strides in understanding the molecular foundations of CSCs have led to preclinical investigations and clinical trials focused on CSC regulator β-catenin signaling targeted interventions in malignancies. As part of the ongoing advancements in marine-organism-derived compound development, it was observed that among the six analogs of Renieramycin T (RT), a potential lead alkaloid from the blue sponge Xestospongia sp., the compound DH_32, displayed the most robust anti-cancer activity in lung cancer A549, H23, and H292 cells. In various lung cancer cell lines, DH_32 exhibited the highest efficacy, with IC50 values of 4.06 ± 0.24 μM, 2.07 ± 0.11 μM, and 1.46 ± 0.06 μM in A549, H23, and H292 cells, respectively. In contrast, parental RT compounds had IC50 values of 5.76 ± 0.23 μM, 2.93 ± 0.07 μM, and 1.52 ± 0.05 μM in the same order. Furthermore, at a dosage of 25 nM, DH_32 showed a stronger ability to inhibit colony formation compared to the lead compound, RT. DH_32 was capable of inducing apoptosis in lung cancer cells, as demonstrated by increased PARP cleavage and reduced levels of the proapoptotic protein Bcl2. Our discovery confirms that DH_32 treatment of lung cancer cells led to a reduced level of CD133, which is associated with the suppression of stem-cell-related transcription factors like OCT4. Moreover, DH_32 significantly suppressed the ability of tumor spheroids to form compared to the original RT compound. Additionally, DH_32 inhibited CSCs by promoting the degradation of β-catenin through ubiquitin-proteasomal pathways. In computational molecular docking, a high-affinity interaction was observed between DH_32 (grid score = -35.559 kcal/mol) and β-catenin, indicating a stronger binding interaction compared to the reference compound R9Q (grid score = -29.044 kcal/mol). In summary, DH_32, a newly developed derivative of the right-half analog of RT, effectively inhibited the initiation of lung cancer spheroids and the self-renewal of lung cancer cells through the upstream process of β-catenin ubiquitin-proteasomal degradation.

Green synthesis of iron oxide nanoparticles from Spermacoce ocymoides Burm.f. plant extracts for targeted lung cancer A549 cell therapy

The present study evaluated the synthesis of iron oxide nanoparticles using Spermacoce ocymoides Burm.f. plant extracts, and the effects of plant based iron oxide nanoparticles on A549 lung cancer cells were investigated to elucidate their impact on cellular morphology, mitochondrial function, and apoptotic pathways. Spermacoce ocymoides plant based iron oxide nanoparticles were characterised by X-ray diffraction, Atomic force microscopy, FTIR, and UV-Vis absorption spectroscopy. Iron oxide nanoparticle treatment caused considerable morphological alterations in A549 cells, including cell shrinkage, detachment, membrane blabbing, and distorted shape, consistent with cellular stress and potential apoptotic events. MMP analysis revealed a dose-dependent decrease in mitochondrial membrane potential, implying that nanoparticles have an effect on mitochondrial function. The presence of reactive oxygen species suggested that oxidative stress was involved in the cellular response to iron oxide nanoparticles. Additionally, DNA fragmentation analysis confirmed the activation of apoptotic pathways, with the nanoparticles themselves serving as a positive control for inducing apoptosis. The observed morphological changes, altered mitochondrial function, ROS production, and DNA fragmentation collectively point towards apoptotic cell death pathways being triggered by the nanoparticles.&#x0D; KEY WORDS: Spermacoce ocymoides, Iron oxide nanoparticles, A549 cells, Apoptotic&#x0D; Bull. Chem. Soc. Ethiop. 2024, 38(1), 123-134. DOI: https://dx.doi.org/10.4314/bcse.v38i1.10

PHRF1 Promotes Cell Invasion by Modulating SOX4 Expression in Colorectal Cancer HCT116-p53-/- Cells.

PHD and RING finger domain-containing protein 1 (PHRF1) ubiquitinates TGIP (TG-interacting protein) and redistributes cPML (cytoplasmic variant of PML) to the cytoplasm to enhance TGF-β signaling by. It is unclear whether PHRF1 affects invasion and survival when both mutations of the activated oncogene Kras and inactivation of the tumor suppressor p53 are present. We knockout PHRF1 expression using Crispr-Cas9 editing in HCT116-p53-/- (KrasG13D/p53-/-) cells and analyzed the expression profile in HCT116-p53-/-PHRF1-/- cells. In contrast to lung cancer A549 (KrasG12S/p53wt) cells, the expression of Zeb1, a transcription factor for epidermal-mesenchymal transition (EMT), was not affected in PHRF1-knockout HCT116 p53-/- cells. Instead, SOX4 displayed a significant contribution to the impaired invasion in HCT116-p53-/-PHRF1-/- cells. Mechanistically, the C-terminal SRI domain of PHRF1 was required for both transwell invasion and SOX4 expression. The reintroduction of SOX4 into HCT116-p53-/- PHRF1-/- cells partially restored their invasive capability. This study sheds light on the role of PHRF1 in the invasion of colorectal cancer HCT116-p53-/- cells, which harbor the oncogenic KrasG13D mutation and lack p53. These findings provide novel insights regarding the role of PHRF1 in invasion by modulating SOX4 expression in colorectal cancer HCT116-p53-/- cells.

Network pharmacology‑based investigation of potential targets of triptonodiol acting on non-small-cell lung cancer

BackgroundTriptonodiol is a very promising antitumor drug candidate extracted from the Chinese herbal remedy Tripterygium wilfordii Hook. F., and related studies are underway.MethodsTo explore the mechanism of triptonodiol for lung cancer treatment, we used network pharmacology, molecular docking, and ultimately protein validation. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through the David database. Molecular docking was performed using PyMoL2.3.0 and AutoDock Vina software. After screening, the major targets of triptonodiol were identified for the treatment of lung cancer. Target networks were established, Protein–protein interaction (PPI) network topology was analyzed, then KEGG pathway enrichment analysis was performed. Useful proteins were screened by survival analysis, and Western blot analysis was performed.ResultsTriptonodiol may regulate cell proliferation, drug resistance, metastasis, anti-apoptosis, etc., by acting on glycogen synthase kinase 3 beta (GSK3B), protein kinase C (PKC), p21-activated kinase (PAK), and other processes. KEGG pathway enrichment analysis showed that these targets were associated with tumor, erythroblastic oncogene B (ErbB) signaling, protein phosphorylation, kinase activity, etc. Molecular docking showed that the target protein GSK has good binding activity to the main active component of triptonodiol. The protein abundance of GSK3B was significantly downregulated in non-small-cell lung cancer cells H1299 and A549 treated with triptonodiol for 24 h.ConclusionThe cellular-level studies combined with network pharmacology and molecular docking approaches provide new ideas for the development and therapeutic application of triptonodiol, and identify it as a potential GSK inhibitor.

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4.

Ropivacaine is a local anesthetic commonly used in regional nerve blocks to manage perioperative pain during lung cancer surgery. Recently, the antitumor potential of ropivacaine has received considerable attention. Our previous study showed that ropivacaine treatment inhibits the malignant behavior of lung cancer cells in vitro. However, the potential targets of ropivacaine in lung cancer cells have not yet been fully identified. This study aimed to explore the antitumor effects and mechanisms of action of ropivacaine in lung cancer. Lung cancer A549 cells were treated with or without 1 mM ropivacaine for 48 h. Quantitative proteomics was performed to identify the differentially expressed proteins (DEPs) triggered by ropivacaine treatment. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and analyze the most significant hub genes. Overexpression plasmids and small interfering RNA were used to modulate the expression of key DEPs in A549 and H1299 cells. MTS, transwell assays, and flow cytometry were performed to determine whether the key DEPs were closely related to the anticancer effect of ropivacaine on the malignant behavior of A549 and H1299 cells. Quantitative proteomic analysis identified 327 DEPs (185 upregulated and 142 downregulated proteins) following ropivacaine treatment. Retinoblastoma-binding protein 4 (RBBP4) was one of the downregulated DEPs and was selected as the hub protein. TCGA database showed that RBBP4 was significantly upregulated in lung cancer and was associated with poor patient prognosis. Inhibition of RBBP4 by siRNA resulted in a significant decrease in the proliferation and invasive capacity of lung cancer cells and the induction of cell cycle arrest. Additionally, the results indicated RBBP4 knockdown enhanced antitumor effect of ropivacaine on A549 and H1299 cells. Conversely, the overexpression of RBBP4 using plasmids reversed the inhibitory effects of ropivacaine. Our data suggest that ropivacaine suppresses lung cancer cell malignancy by downregulating RBBP4 protein expression, which may help clarify the mechanisms underlying the antitumor effects of ropivacaine.