Lung Cancer Cell Lines Research Articles

A comparative study of circulating tumor cell isolation and enumeration technologies in lung cancer.

Circulating tumor cells (CTCs) have potential as diagnostic, prognostic, and predictive biomarkers in solid tumors. Despite Food and Drug Administration (FDA) approval of CTC devices in various cancers, the rarity and heterogeneity of CTCs in lung cancer make them technically challenging to isolate and analyze, hindering their clinical integration. Establishing a consensus through comparative analysis of different CTC systems is warranted. This study aimed to evaluate seven different CTC enrichment methods across five technologies using a standardized spike-in protocol: the CellMag™ (EpCAM-dependent enrichment), EasySep™ and RosetteSep™ (blood cell depletion), and the Parsortix® PR1 and the new design Parsortix® Prototype (PP) (size- and deformability-based enrichment). The Parsortix® systems were also evaluated for any differences in recovery rates between cell harvest versus in-cassette staining. Healthy donor blood (5 mL) was spiked with 100 fluorescently labeled EpCAMhigh H1975 cells, processed through each system, and the isolation efficiency was calculated. The CellMag™ had the highest recovery rate (70 ± 14%), followed by Parsortix® PR1 in-cassette staining, while the EasySep™ had the lowest recovery (18 ± 8%). Additional spike-in experiments were performed with EpCAMmoderate A549 and EpCAMlow H1299 cells using the CellMag™ and Parsortix® PR1 in-cassette staining. The recovery rate of CellMag™ significantly reduced to 35 ± 14% with A549 cells and 1 ± 1% with H1299 cells. However, the Parsortix® PR1 in-cassette staining showed cell phenotype-independent and consistent recovery rates among all lung cancer cell lines: H1975 (49 ± 2%), A549 (47 ± 10%), and H1299 (52 ± 10%). Furthermore, we demonstrated that the Parsortix® PR1 in-cassette staining method is capable of isolating heterogeneous single CTCs and cell clusters from patient samples. The Parsortix® PR1 in-cassette staining, capable of isolating different phenotypes of CTCs as either single cells or cell clusters with consistent recovery rates, is considered optimal for CTC enrichment for lung cancer, albeit needing further optimization and validation.

DOTAP Modified Formulations of Aminoacid Based Cationic Liposomes for Improved Gene Delivery and Cell Viability.

The liposomal systems proved remarkably useful for the delivery of genetic materials but enhancing their efficacy remains a significant challenge. While structural alterations could result in the discovery of more effective transfecting lipids, improving the efficacy of widely used lipid carriers is also crucial in order to compete with viral vectors for gene delivery. Herein, we developed formulations of commercially available lipid, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) with synthetic cationic lipids containingamino acids, cystine (CTT) or arginine (AT) in the head group. These lipids were used to formulatewith different co-lipid compositions and werebroadly categorised into two types: amino acid-based liposomes without DOTAP (CTTD and ATD) and those with DOTAP (DtATD and DtCTTD). Optimized lipid-DNA complexes of DOTAP-incorporated formulations (DtATD and DtCTTD) exhibited enhanced efficacy in transfection compared to formulations lacking DOTAP as well as commercial formulations such as DOTAP:DOPE. Notably, DtCTTD displayed superior transfection capabilities in prostate cancer (PC3) and lung cancer (A549) cell lines when compared to the widely used commercial transfection reagent, Lipofectamine. Collectively, the findings from this study suggest that DOTAP-incorporated formulations derived from amino acid-based liposomes, hold promise as effective tools for improving transfection efficacy with reduced toxicity, offering potential advancements in gene delivery applications.

Identification of resistance mechanisms to small-molecule inhibition of TEAD-regulated transcription

The Hippo tumor suppressor pathway controls transcription by regulating nuclear abundance of YAP and TAZ, which activate transcription with the TEAD1-TEAD4 DNA-binding proteins. Recently, several small-molecule inhibitors of YAP and TEADs have been reported, with some entering clinical trials for different cancers with Hippo pathway deregulation, most notably, mesothelioma. Using genome-wide CRISPR/Cas9 screens we reveal that mutations in genes from the Hippo, MAPK, and JAK-STAT signaling pathways all modulate the response of mesothelioma cell lines to TEAD palmitoylation inhibitors. By exploring gene expression programs of mutant cells, we find that MAPK pathway hyperactivation confers resistance to TEAD inhibition by reinstating expression of a subset of YAP/TAZ target genes. Consistent with this, combined inhibition of TEAD and the MAPK kinase MEK, synergistically blocks proliferation of multiple mesothelioma and lung cancer cell lines and more potently reduces the growth of patient-derived lung cancer xenografts in vivo. Collectively, we reveal mechanisms by which cells can overcome small-molecule inhibition of TEAD palmitoylation and potential strategies to enhance the anti-tumor activity of emerging Hippo pathway targeted therapies.

2-Chloro-3-cyano-4-nitrobenzyl pyridinium bromide as a potent anti-lung cancer molecule prepared using a single-step solvent-free method.

Mono-/dimeric-substituted pyridinium and pyrazolium bromides were prepared under conventional and solvent-free silica-supported domestic microwave conditions. The atom economy, environmental product mass intensity and product mass intensity for solvent-free reactions showed significant importance for the synthesis of target molecules. 4-Nitrobenzyl-substituted pyridinium bromide showed potent anticancer properties compared with mono-/dimeric-substituted pyridinium and pyrazolium bromides against a lung cancer cell line (A-549). Molecular simulation studies were carried out for mono-/dimeric-substituted pyridinium and pyrazolium bromide against protein human CDK1/cyclinB1/CKS2 using the AutoDock program.

ATF1 promotes ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2

BackgroundFerroptotic proteins are promising therapeutic targets for lung cancer. The PROM2 is upregulated in lung cancer and known to suppress ferroptosis. This study examined the molecular mechanisms for PROM2-induced ferroptosis resistance in lung cancer. MethodsFerroptosis in lung cancer was assessed by iron kit, and transmission electron microscopy was applied to observe the changes in mitochondrial morphology. BODIPY™ was applied to test the lipid ROS, and MeRIP was performed to test the m6A modification of PROM2. RIP assay was employed for confirming the binding between METTL3 and PROM2. In addition, dual luciferase assay was employed for exploring the transcriptional regulation of ATF1 to METTL3, and the binding relation between ATF1 and METTL3 promoter region was explored by ChIP assay. ResultsExpression levels of PROM2 were significantly higher in lung cancer cell lines than a noncancerous control line, and PROM2 knockdown significantly reduced both cancer cell viability and proliferation rate. In addition, PROM2 knockdown reduced xenograft tumor growth and exacerbated erastin-induced ferroptosis. Compared to PROM2 mRNA from control cells, transcripts in lung cancer cells exhibited enhanced m6A levels, and showed greater binding with METTL3. Further, ATF1 upregulated METTL3 transcription, thereby stabilizing PROM2 mRNA and increasing ferroptosis resistance. ConclusionATF1 could promote ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2. Thus, our work might shed novel insights on discovering therapeutic strategy for lung cancer.

Nano-Liposomal Beetroot Phyto-Pigment in Photodynamic Therapy as a Prospective Green Approach for Cancer Management: In Vitro Evaluation and Molecular Dynamic Simulation.

Using plant extracts as photosensitizers in photodynamic therapy (PDT) represents a significant green approach toward sustainability. This study investigates beetroot juice (BRJ), betanin, and their liposomal formulations (Lip-BRJ, Lip-Bet) as photosensitizers in cancer PDT. BRJ was prepared, and its betanin content was quantified via HPLC. The p-nitrosodimethylaniline (RNO)/imidazole technique monitored the singlet oxygen formation. BRJ and betanin decreased the RNO absorbance at 440 nm by 12% and 9% after 45 min of irradiation, respectively. Furthermore, betanin interaction with Bcl-2 proteins was examined using binding free energy analysis and molecular dynamic simulation. The results revealed favorable interactions with ΔG values of -40.94 kcal/mol. Then, BRJ, betanin, Lip-BRJ, and Lip-Bet were tested as photosensitizers on normal (HEK 293) and human lung cancer (A549) cell lines. Irradiation significantly enhanced the cytotoxicity of Lip-Bet on HEK 293 cells (20% cell viability at 2000 µg/mL) and A549 cells (13% cell viability at 1000 µg/mL). For Lip-BRJ, irradiation significantly enhanced the cytotoxicity on HEK 293 cells at lower concentrations and on A549 cells at all tested concentrations. These results proved the positive effect of light and liposomal encapsulation on the anticancer activity of betanin and BRJ, suggesting the efficiency of liposomal beetroot pigments as green photosensitizers.

Evaluation of Cytotoxic and Anti-cancer Potential of Capsaicin on Lung Cancer Cell Line: An In Vitro Investigation.

Background The leading cause of cancer-related deaths worldwide is lung cancer. Approximately 1.8 million new cases were diagnosed, and 1.6 million individuals died. Available treatment options are inefficient leading to tumour recurrence. Hence there is a need for novel therapeutic advancements in lung cancer treatment. Capsaicin, a naturally occurring protoalkaloid, was found to possess several potential benefits. Aim The aim of the study was toexamine capsaicin's cytotoxic and anti-cancer effects in the lung cancer cell line (A549). Materials and methods The cell viability of lung cancer cells treated with capsaicin was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A549 cells were treated with capsaicin at concentrations ranging from 25 to 150 µM/mL for 24 hours. Changes in cell morphology were observed using a phase-contrast microscope. Nuclear morphological alterations in the lung cancer cells were examined through acridine orange/ethidium bromide (AO/EtBr) staining and viewed under a fluorescent microscope to identify apoptotic nuclei. Gene expression analysis was performed using quantitative real-time PCR (Polymerase Chain Reaction) to evaluate the expression of apoptotic genes, transforming growth factor-beta (TGF-β), and suppressor of mothers against decapentaplegic 2 (SMAD2). Capsaicin's anti-migratory properties were assessed using a scratch wound healing assay. Result Our study demonstrated that treating lung cancer cells with capsaicin dramatically decreased their vitality, with a statistically significant difference (p<0.05) between the treatment and control groups. In lung cancer cells, we measured the inhibitory concentration (IC-50) at 101.2μM/ml. Following treatment, the number of cells decreased, and those that remained exhibited cytoplasmic membrane blebbing and shrunk. With AO/EtBr staining, treated cells showed an increased number of apoptotic cells. The study's findings showed that after receiving capsaicin, there was a significant downregulation of TGF-β and SMAD2. Moreover, when compared to control cells, capsaicin-treated cells' migration was markedly reduced. Through modification of the TGF-β/SMAD2 signaling system, capsaicin therapy dramatically promotes apoptosis and inhibits migration. Conclusion In conclusion, the study's results indicate that capsaicin may have anti-tumor effects on lung cancer cells. To fully comprehend the mechanism underlying capsaicin's anticancer potential and its therapeutic application, further studies are much needed.

Impact of Modified ZnO Nanoparticles on Immune Response in Mouse Lung Cancer Model

Background: Lung cancer, which is characterized by the presence of malignant tumors, offers a potential avenue for treatment through the use of nanomedicines. Previous in vitro studies have shown promising effects of modified zinc oxide nanoparticles on lung cancer cell lines. Accordingly, this study investigates the impact of this nanodrug on the immune response in a mouse model of lung cancer. Materials and Methods: In this study, a mouse model of lung cancer was utilized. Various aspects, including tumor size, infiltration of CD8+ cells and the survival rate of the mice, were carefully examined. The obtained results were subsequently analyzed using the GraphPrism software, version 9. Results: Mice treated with the nanodrug exhibited a reduction in tumor size. Additionally, there was an increase in the number of CD8+ cells infiltrating the tissue. Furthermore, the administration of the nanodrug led to improved survival rates among the mice. Conclusion: The use of this nanodrug has shown significant efficacy in inhibiting tumor growth. Moreover, it has demonstrated potential in enhancing CD8+ cell infiltration, thereby strengthening the immune response and suppressing tumor progression. Ultimately, this nanodrug improves the survival of mice receiving treatment.

Epithelium/imcDC2 axis facilitates the resistance of neoadjuvant anti-PD-1 in human NSCLC

BackgroundTherapeutic resistance is a main obstacle to achieve long-term benefits from immune checkpoint inhibitors. The underlying mechanism of neoadjuvant anti-PD-1 resistance remains unclear.MethodsMulti-omics analysis, including mass cytometry, single-cell RNA-seq, bulk...

In vitro cancer cell line luminescence-based validation of anticancer phytocompounds obtained from Leucas biflora against HELA cervical and A549 lung cancer cells.

Current research aims to screen the anticancer prospective of Leucas biflora phytocompounds against apoptotic regulator target protein essential for cancer progression. In gas chromatography-mass spectrometry analysis major phytocompounds such as tetracosahexaene, squalene, phytol, 22-stigmasten-3-one, stigmasterol, fluorene, and 1,4-dihydro were identified in ethanolic leaf extract of Leucas biflora. In vitro, the free radical scavenging potential of ethanolic leaf extract of Leucas biflora was examined through its DPPH and ABTS radical scavenging potential IC50 value 15.35 and 13.20 μg/ml, respectively. Dose-dependent cytotoxicity was monitored against both A549 lung cancer and HELA cervical cancer cells. Leucas biflora ethanolic leaf extract highly reduces the cell viability of both HELA and A549 cells in in vitro cytotoxicity assays. Leucas biflora ethanolic extract produces 23.76% and 29.76% viability rates against A549 lung and HELA cervical cancer cell lines, and their IC50 values differ slightly at 95.80 and 90.40 μg/ml, respectively. In molecular docking analysis lung cancer target protein-ligand complex 5Y9T-16132746 showed a maximum score of -14 kcal/mol by exhibiting stable binding affinity and interactions among all screened complexes. Based on docking score nine phytocompounds from Leucas biflora and two reference standard drugs were chosen for further analysis. Further validation reveals that the fluorene, 1,4-dihydro possess good ADMET, Bioactivity and density functional theory indices.

Repurposing Suan-Zao-Ren-Tang as anticancer agents in apoptotic sensitization against non-small cell lung cancer cell lines through amplification of spindle assembly checkpoint activation

Treatment of non-small cell lung cancer (NSCLC) is a high unmet medical need. We repurposed Suan-Zao-Ren-Tang (SZRT), a widely used traditional Chinese medicine in alleviating insomnia, to sensitize vinorelbine-induced anti-NSCLC effect and have unveiled the underlying mechanism. B7E2, the partial purified extract from SZRT, was used through bioactivity-guided fractionation based on anti-proliferative activity in NSCLC cell lines A549 and NCI-H460. Three batches of B7E2 and their individual components were prepared for the examination of components and bioactivity and mechanistic study. B7E2 alone had no cytotoxic effect but its combination with vinorelbine displayed a synergistic activity in killing NSCLC cells. Apoptotic sensitization was verified by a remarkable increase of caspase activation and phosphorylation of Bcl-2 and Bcl-xL. Combination treatment prolonged mitotic arrest and induced a substantial activation of spindle assembly checkpoint (SAC) characterized by BUBR1 phosphorylation at Ser670 and Thr680, and cyclin B1 upregulation. Combination treatment enhanced the interaction between mitotic checkpoint complex (MCC) components, including BUBR1, MAD2, BUB3 and CDC20. Further analysis revealed that SZRT components, including senkyunolide-A, trans-neocnidilide, 3-butylidenephthalide, betulinic acid and linoleic acid, were responsible for B7E2 activities. Three B7E2 batches showed a good chemical similarity and similar activities between batches. The data suggest that B7E2 is a potential chemosensitizer in potentiating vinorelbine-induced anti-NSCLC activity through amplification and prolongation of SAC activation.

Downregulation of 4-HNE and FOXO4 collaboratively promotes NSCLC cell migration and tumor growth

Non-small cell lung cancer (NSCLC) is among the most prevalent cancers and a leading cause of cancer-related mortality globally. Extracellular vesicles (EVs) derived from NSCLC play a pivotal role in lung cancer progression. Our findings reveal a direct correlation between the abundance of EVs and the transfection efficiencies. Co-culturing two different lung cancer cell lines could enhance EVs formation, cell proliferation, migration and tumorigenicity. mRNA chip and metabolic analyses revealed significant alterations in the FOXO signaling pathway and unsaturated fatty acid metabolism within tumor tissues derived from co-cultured cells. Shotgun lipidomics studies and bioinformatics analyses guided our attention towards 4-Hydroxynonenal (4-HNE) and FOXO4. Elevating 4-HNE or FOXO4 levels could reduce the formation of EVs and impede cell growth and migration. While silencing FOXO4 expression lead to an increase in cell cloning rate and enhanced migration. These findings suggest that regulating the production of 4-HNE and FOXO4 might provide an effective therapeutic approach for the treatment of NSCLC.

In vitro Cytotoxic and Anti-ROS Potentials of the Aerial Part of Pyrrosia lanceolata on A549 Cells and Cell Free Condition

Antioxidants and cancer are somewhat related to each other. The study was designated to evaluate the antioxidant activities of the aerial parts of Pyrosia lanceolata (P. lanceilata, Fam. Polypodiaceae) and their cytotoxic potential in a lung cancer cell line (A549). The extraction of plant material was performed by using methanol (CME), followed by solvent-solvent partitioning with different solvents. The methanol (CME) and its subsequent fractions (pet-ether PEF, chloroform CHF, ethyl acetate EAF and aqueous AQF fractions) confirmed the presence of alkaloids, flavonoids, phenols, tannins and terpenoids at different degrees. The phenolic and flavonoid content were found to be 69.46, 37.93, 64.61, 126.74 and 60.64 mg of GAE/gm and 33.93, 4.11, 45.68, 146.95, and 44.36 mg of CAE/gm of dried CME, PEF, CHF, EAF and AQF, respectively. The overall antioxidant and iron reduction capacities of CME and all the fractions were in the following order: EAF &gt; CHF &gt; CME &gt; AQF &gt; PEF and EAF &gt; CHF &gt; CME &gt; AQF &gt; PEF, respectively. Among the fractions, EAF significantly scavenged DPPH (IC50 of 1.34 μg/ml) and OH radicals (IC50 of 4.38 μg/ml), which closely resembled those of standard BHT (IC50 of 0.9 μg/ml) and CA (IC50 of 2.73 μg/ml), respectively. Moreover, EAF (IC50 of 14.06 μg/ml) demonstrated a similar effect on inhibiting lipid peroxidation when compared to standard CA (IC50 of 13.86 μg/ml). In addition, CHF (24.25%) and EAF (14.9%) showed a potent cytotoxic effect in A549 cells. Our results suggest that P. lanceolata might be a good source of anticancer potential having antioxidant activity. Bangladesh Pharmaceutical Journal 27(2): 137-148, 2024 (July)

SAFER: sub-hypergraph attention-based neural network for predicting effective responses to dose combinations

BackgroundThe potential benefits of drug combination synergy in cancer medicine are significant, yet the risks must be carefully managed due to the possibility of increased toxicity. Although artificial intelligence applications have demonstrated notable success in predicting drug combination synergy, several key challenges persist: (1) Existing models often predict average synergy values across a restricted range of testing dosages, neglecting crucial dose amounts and the mechanisms of action of the drugs involved. (2) Many graph-based models rely on static protein–protein interactions, failing to adapt to dynamic and higher-order relationships. These limitations constrain the applicability of current methods.ResultsWe introduce SAFER, a Sub-hypergraph Attention-based graph model, addressing these issues by incorporating complex relationships among biological knowledge networks and considering dosing effects on subject-specific networks. SAFER outperformed previous models on the benchmark and the independent test set. The analysis of subgraph attention weight for the lung cancer cell line highlighted JAK-STAT signaling pathway, PRDM12, ZNF781, and CDC5L that have been implicated in lung fibrosis.ConclusionsSAFER presents an interpretable framework designed to identify drug-responsive signals. Tailored for comprehending dose effects on subject-specific molecular contexts, our model uniquely captures dose-level drug combination responses. This capability unlocks previously inaccessible avenues of investigation compared to earlier models. Furthermore, the SAFER framework can be leveraged by future inquiries to investigate molecular networks that uniquely characterize individual patients and can be applied to prioritize personalized effective treatment based on safe dose combinations.

Utilizing biosynthesized nickel(II) oxide nanoparticles in the synthesis of bis(indolyl)arylmethanes with anti-lung cancer properties

The recently prepared nanophotocatalyst Ni-NiO is introduced as an effective mediator in the one-pot two-component synthesis of various substituted bis(indolyl)arylmethanes and as potent anti-lung cancer agent. The inception of this environmental friendly photocatalyst stems from the biosynthesis process utilizing Glycyrrhiza Glabra (licorice) leaves extract that is an active plant with potential applications in lung cancer treatment. Familiar characterization techniques including XPS, UV–Vis, XRD, FT-IR, FE-SEM, TEM, and EDS provided a comprehensive information on the physicochemical properties of Ni-NiO nanoparticles. Subsequently, the Ni-NiO nanophotocatalyst was harnessed for the synthesis of bis(indolyl)arylmethanes under visible light. The utilized photocatalyst underscored reasonable stability, reusability, and practical utility. Moreover, cytotoxicity evaluations employing the MTT experiment on A549 lung cancer cell line proved promising potential of Ni-NiO nanoparticles and bis(indolyl)phenylmethane in inhibiting cancer cell proliferation. Findings revealed that both biosynthesized Ni-NiO nanoparticles and the tested bis(indolyl)phenylmethane have sufficient therapeutic potential against the performed cancer cell line. This innovative approach represents a significant contribution to the field of cancer research and underscores the potential for developing next-generation cancer treatments.

PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer

BackgroundLung cancer stands as the second most prevalent malignant neoplasm worldwide. Addressing the underlying mechanisms propelling the progression of non-small cell lung cancer is of paramount importance. In this study, we have elucidated the pivotal role of PHF12 in this context.Materials and methodsWe harnessed clinical lung cancer tissue samples and non-small cell lung cancer cell lines to discern the expression pattern of PHF12. In vitro assays probing cell proliferation were conducted to substantiate the functional impact of PHF12. Furthermore, an in vivo Xenograft model was employed to dissect the role of PHF12. Employing ChIP assays and qRT-PCR, we delved into the intricate binding dynamics between PHF12 and HDAC1. Mechanistic insights into the PHF12-HDAC1 axis in lung cancer progression were pursued via RNA-seq and GSEA analyses.ResultsNotably, PHF12 exhibited a substantial upregulation within tumor tissue, concomitant with its correlation to HDAC1. The trilogy of cell proliferation assays, transwell assays, and the Xenograft model collectively underscored the promoting influence of PHF12 on lung cancer proliferation, both in vitro and in vivo. The ChIP assay unveiled the transcriptional regulatory role of PHF12 in governing HDAC1 expression. This correlation extended to both mRNA and protein levels. PHF12 promotes NSCLC progression through regulating HDCA1 expression. Intriguingly, the rescue of function within NSCLC cell lines post PHF12 knockdown was achievable through HDAC1 overexpression. Additionally, our findings unveiled the capacity of the PHF12-HDAC1 axis to activate the EGFR/AKT signaling pathway, thereby further corroborating its significance in lung cancer progression.ConclusionOur study identified PHF12 as an oncogenic role in lung cancer proliferation and migration for the first time. PHF12 transcriptionally regulate HDAC1 and activate EGFR/AKT signaling pathway in NSCLC progression. PHF12 may serve as an important target in lung cancer therapy.

In vitro cytotoxic activity of chemically synthesized ZnTe nanoparticles against human lung cancer cell line L-132 with supported molecular docking study

Among all the cancer cases, Lung cancer is the most common worldwide, which needs more potential therapy. But there are many limitations in the present therapy used for lung cancer treatment. Recently, many researchers are using different types of nanoparticles as an alternative for this purpose. Here, with such interest, ZnTe nanocrystals have been synthesized using a wet-chemical method, which is a cost-effective and easy method. After preparing the ZnTe nanocrystals, morphology has been analyzed through a scanning electron microscope (SEM) and the crystallinity of the prepared ZnTe nanocrystals has been investigated using X-ray diffraction analysis. After that, cytotoxicity of the prepared ZnTe nanoparticles has been examined at three different concentrations (100 ng/ml, 1 μg/ml, 100 μg/ml) on human lung cancer cell line L-132 using the MTT assay. From the experimental results, it is observed that a batter percentage of about 56 % of killing has been obtained at the concentration of 100 μg/ml after 24 h of treatment. It may happen that ZnTe nanoparticles enter through the cell membrane and induce cell apoptosis. For better understanding, molecular docking has been performed using ‘auto dock vina’ to find the binding confirmation of ZnTe nanoparticles with the lung cancer cell line L-132. Both the biological and computational methods confirm that nanocrystalline ZnTe is a therapeutic candidate for the treatment of lung cancer cells.

Synthesis of chitosan polyethylene glycol antibody complex for delivery of Imatinib in lung cancer cell lines.

Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second-line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non-small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS-PEG-Ab-Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS-PEG-Ab-Im was 25-30 nm, its surface charge was 13.1 mV, and the shape of CS-PEG-Ab-Im was nearly spherical and cylindrical. The therapeutic potential of CS-PEG-Ab-Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS-PEG-Ab-Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS-PEG-Ab-Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS-PEG-Ab. Besides, cell arresting result exhibits the CS-PEG-Ab-Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS-PEG-Ab-Im can be an ideal nanosystem in NSCLC treatment.

Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds

BackgroundTumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult to study. Unfortunately, model systems to functionally characterize and mechanistically study dynamic responses to treatment across coexisting subpopulations of cancer cells remain a missing need in oncology.MethodsUsing single cell cloning and expansion techniques, we established monoclonal cell subpopulations (MCPs) from a commercially available epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer cell line. We then used this model sensitivity to the EGFR inhibitor osimertinib across coexisting cell populations within the same tumor. Pathway-centered signaling dynamics associated with response to treatment and morphological characteristics of the MCPs were assessed using Reverse Phase Protein Microarray. Signaling nodes differentially activated in MCPs less sensitive to treatment were then pharmacologically inhibited to identify target signaling proteins putatively implicated in promoting drug resistance.ResultsMCPs demonstrated highly heterogeneous sensitivities to osimertinib. Cell viability after treatment increased > 20% compared to the parental line in selected MCPs, whereas viability decreased by 75% in other MCPs. Reduced treatment response was detected in MCPs with higher proliferation rates, EGFR L858R expression, activation of EGFR binding partners and downstream signaling molecules, and expression of epithelial-to-mesenchymal transition markers. Levels of activation of EGFR binding partners and MCPs’ proliferation rates were also associated with response to c-MET and IGFR inhibitors.ConclusionsMCPs represent a suitable model system to characterize heterogeneous biomolecular behaviors in preclinical studies and identify and functionally test biological mechanisms associated with resistance to targeted therapeutics.

Molecular Hybrid Design, Synthesis, In Vitro Cytotoxicity, In Silico ADME and Molecular Docking Studies of New Benzoate Ester-Linked Arylsulfonyl Hydrazones.

In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9-20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9-20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9-20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9-20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9-20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59-176.70 μM for the A549 cell line and 27.70-170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 μM against A549 cell line and IC50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 μM against A549 cell line and IC50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski's rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.