Characterization, biological activity, and anticancer effect of green-synthesized gold nanoparticles using Nasturtium officinale L.

BACKGROUND: Nanostructured materials used have unique properties and many uses in nanotechnology. The most striking of these is using herbal compounds for the green synthesis of nanoparticles. Among the nanoparticle types used for green synthesis, gold nanoparticles (AuNPs) are used for cancer therapy due to their stable structure and non-cytotoxic. Lung cancer is the most common and most dangerous cancer worldwide in terms of survival and prognosis. In this study, Nasturtium officinale (L.) extract (NO), which contains biomolecules with antioxidant and anticancer effects, was used to biosynthesize AuNPs, and after their characterization, the effect of the green-synthesized AuNPs against lung cancer was evaluated in vitro. METHODS: Ultraviolet‒visible (UV‒Vis) spectrophotometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), multiple analysis platform (MAP), and Fourier transform infrared (FT-IR) spectroscopy analyses were performed to characterize the AuNPs prepared from the N. officinale plant extract. Moreover, the antioxidant activity, total phenolic and flavonoid contents and DNA interactions were examined. Additionally, A549 lung cancer cells were treated with 2-48 µg/mL Nasturtium officinale gold nanoparticles (NOAuNPs) for 24 and 48 h to determine the effects on cell viability. The toxicity of the synthesized NOAuNPs to lung cancer cells was determined by the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay, and the anticancer effect of the NOAuNPs was evaluated by apoptosis and cell cycle analyses using flow cytometry. RESULTS: The average size of the NPs was 56.4 nm. The intensities of the Au peaks from EDS analysis indicated that the AuNPs were synthesized successfully. Moreover, the in vitro antioxidant activities of the NO and NOAuNPs were evaluated; these materials gave values of 31.78 ± 1.71% and 31.62 ± 0.46%, respectively, in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay at 200 g/mL and values of 25.89 ± 1.90% and 33.81 ± 0.62%, respectively, in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The NO and NOAuNPs gave values of 0.389 ± 0.027 and 0.308 ± 0.005, respectively, in the ferrous ion reducing antioxidant capacity (FRAP) assay and values of 0.078 ± 0.009 and 0.172 ± 0.027, respectively, in the copper ion reducing antioxidant capacity (CUPRAC) assay. When the DNA cleavage activities of NO and the NOAuNPs were evaluated via hydrolysis, both samples cleaved DNA starting at a concentration of 25 g/mL in the cell culture analysis, while the nanoformulation of the NO components gave greater therapeutic and anticancer effects. We determined that the Au nanoparticles were not toxic to A549 cells. Moreover, after treatment with the half-maximal inhibitory concentration (IC50), determined by the MTT assay with A549 cells, we found that at 24 and 48 h, while the necrosis rates were high in cells treated with NO, the rates of apoptosis were greater in cells treated with NOAuNPs. Notably, for anticancer treatment, activating apoptotic pathways that do not cause inflammation is preferred. We believe that these results will pave the way for the use of NOAuNPs in in vitro studies of other types of cancer. CONCLUSION: In this study, AuNPs were successfully synthesized from N. officinale extract. The biosynthesized AuNPs exhibited toxicity to and apoptotic effects on A549 lung cancer cells. Based on these findings, we suggest that green-synthesized AuNPs are promising new therapeutic agents for lung cancer treatment. However, since this was an in vitro study, further research should be performed in in vivo lung cancer models to support our findings and to explain the mechanism of action at the molecular level.

In silico and in vitro studies of Tyr-Lys-Thr tripeptide against human lung cancer cell line (A549).

OBJECTIVES: The main purpose of this study is to predict the effect of Tyr-Lys-Thr (YKT) tripeptide, recognized for its anticancer properties, on lung cancer through theoretical and experimental analyzes. BACKGROUND: Peptides are important therapeutic compounds that have been studied for many years. Among these, YKT tripeptide emerges as a significant therapeutic peptide, exhibiting cytotoxic effects on various cancer cell lines. METHODS: The study investigated the involvement of the PI3K/Akt/mTOR pathway, commonly activated in human cancer, and the pivotal role of caspases in apoptosis. The interactions of YKT tripeptide with mTOR, Akt, PI3K, caspase-3, and caspase-8 were investigated through the molecular docking method. Additionally, MTT test was used to determine the cytotoxic activity of YKT against the A549 cell line across concentrations set at 0.1, 0.25, 0.5, 1, 2.5 and 5 mg/mL for 24 and 48 h. RESULTS AND CONCLUSION: In silico docking studies were conducted with PI3K, Akt1, and mTOR, known to be active in human cancer, as well as caspase-3 and caspase-8, key enzymes in apoptosis. It was determined that YKT exhibited a robust binding tendency with each receptor. YKT tripeptide was also found to have a cytotoxic effect on human lung carcinoma cell line A549 (Tab. 5, Fig. 11, Ref. 28).

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 to examine 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-ß), 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-ß and SMAD2. Moreover, when compared to control cells, capsaicin-treated cells' migration was markedly reduced. Through modification of the TGF-ß/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.

Cytotoxic and ROS generation activity of anthraquinones chelate complexes with metal ions.

Anthraquinones (AQs) are very effective chemotherapeutic agent, however their fundamental shortcoming is high cardiotoxicity caused by reactive oxygen species (ROS). Therefore, development of improved antitumor drugs with enhanced efficacy but reduced side effects remains a high priority. In the present study we evaluated the cytotoxicity and ROS generation activity of chelate complex of redox-active anthraquinone 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione (Q1) with iron and copper ions. Cytotoxicity study was performed using the lung cancer cell line A549 and breast cancer cell line MDA-MB-231. Q1 and Cu-Q1 complex demonstrate high activity in these experiments, but Fe-Q1 complex inactive. The ROS generation activity has been studied by EPR spin trapping technique using A549, MDA-MB-231 cell lines, and T lymphoblast cell line MOLT-4. It was shown that Q1 is able to penetrate into these cells and participate in redox reactions with the formation of a semiquinone radical. Fe(III) chelate complex formation results in much slower kinetics of ROS generation compared with pure Q1, which could be connected with a lower penetration through the cell membrane.

Investigation of the anticancer effect of newly synthesized palladium conjugate Schiff base metal complexes on non-small cell lung cancer cell line and mouse embryonic fibroblast cell line.

Lung cancer remains one of the leading causes of death worldwide. Due to the side effects of chemotherapeutic agents on normal cells and the development of resistance by cancer cells, there is an urgent need for alternative new pharmacological agents. Palladium (Pd)-conjugated Schiff base (SB) compounds represent an alternative approach with promising potential applications in cancer treatment. This study aims to identify novel therapeutic agents on A549 cells through the synthesis and characterization of Schiff base conjugated-Palladium complexes (Pd-L1 and Pd-L2). Additionally, it seeks to elucidate the mechanism of action of these compounds on both the A549 and NIH/3T3 cell lines. In the present study, two new Pd-L1 and Pd-L2 were synthesized for the first time and characterized mainly by single crystal X-ray diffraction and 1H, 13C, 31P NMR techniques. The cytotoxic effect of the compounds was evaluated by MTT assay on A549 and NIH/3T3 cell lines for 24 and 48 h. Cisplatin was used as a positive control group. Based on the cytotoxicity results, the complexes were evaluated for their anticancer activities against A549 cell lines for 48 h through reactive oxygen species (ROS), cell cycle, apoptotic, and necrotic cell analyses. The most potent cytotoxic effects were determined for Pd-L1 (IC50: 23.33 µM), Pd-L2 (IC50: 3.19 µM), and cisplatin (IC50: 33.27 µM) on A549 cells (p < 0.05). The compounds exhibited a significant cytotoxic effect at lower concentrations on A549 cells compared to NIH/3T3 cells (p < 0.05). All compounds showed a significant increase in ROS levels in A549 cells compared to the control group (p < 0.05). While necrosis and apoptosis was observed in A549 cells treated with cisplatin, induction of apoptosis was effective in cell death for A549 cells treated with Pd-L1 and Pd-L2 (p < 0.05). Additionally, it was observed that the compounds inhibited cell proliferation in the G0/G1 and G2/M cell cycle phases (p < 0.05). All compounds induced cell cycle arrest and cell death in A549 cells by increasing ROS levels. The results obtained in the present study could advance the utilization of the compounds as anticancer agents.

Exploring the uncharted seas: Metabolite profiling unleashes the anticancer properties of Oscillatoria salina.

Marine cyanobacteria offer a rich source of varied natural products with both chemical and biological diversity. Oscillatoria salina (O. salina) is a filamentous non-heterocystous marine cyanobacterium from Oscillatoriaceae family. In this investigation, we have unveiled bioactive extracts from O. salina using two distinct solvent systems, revealing significant anticancer properties. Our assessment of the organic and aqueous extracts (MCE and AE) of O. salina demonstrated pronounced antiproliferative and antimetastatic effects. Notably, this study is the first to elucidate the anticancer and anti-metastatic potential of O. salina extracts in both 2D and 3D cell culture models. Both MCE and AE induced apoptosis, hindered cell proliferation, invasion, and migration in A549 non-small cell lung cancer cells, accompanied by alterations in cell morphology and cytoskeleton collapse. Moreover, MCE and AE induced spheroid disintegration in A549 cells. Transcriptomics analysis highlighted the significant involvement of Rap1 and p53 signaling pathways in mediating the observed antitumor effects. Mass spectroscopy characterization of these extracts identified 11 compounds, some known for their anticancer potential. HPLC analysis of AE revealed six peaks with UV absorption spectra resembling phycocyanin, a cyanobacterial pigment with well-known anticancer activity. Collectively, these findings underscore the anticancer potential of MCE and AE, containing bioactive metabolites with anticancer and antimetastatic properties.

New 6-nitro-4-substituted quinazoline derivatives targeting epidermal growth factor receptor: design, synthesis and in vitro anticancer studies.

Aim: Twenty compounds of 6-nitro-4-substituted quinazolines were synthesized.Materials & methods: The new derivatives were evaluated for their epidermal growth factor receptor (EGFR) inhibitory activity. The most potent derivatives were assessed for their cytotoxicity against colon cancer and lung cancer cells, in addition to normal fibroblast cells.Results & discussion: compound 6c showed a superior to nearly equal cytotoxicity in comparison to gefitinib, it also revealed a good safety profile. Compound 6c caused a cell cycle arrest at G2/M phase in addition to induction of apoptosis. A molecular docking study was conducted on the most active compounds to gain insights of their binding mode in the active site of EGFR enzyme besides ADME prediction of their physicochemical properties and drug likeness profile.

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Mechanistic insights into Retama raetam's anti-proliferative and pro-apoptotic effects in A549 lung cancer cells: targeting PI3K/Akt pathway and ROS production.

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths worldwide. This study investigates the molecular mechanisms behind the anti-cancer effects of the tropical desert plant Retama raetam (R. raetam) on the A549 NSCLC cell line. The research examined R. raetam's anti-proliferative effects, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and cell morphology in NSCLC A549 and L-132 cells. In addition, the influence of R. raetam on DNA fragmentation, apoptotic signaling, and PI3K/Akt pathways for its anti-cancer mechanism was examined. Our results indicated that R. raetam's effects were dose- and time-dependent to exhibit anti-proliferative effects on A549 cells. R. raetam treatment promoted apoptotic cell death cycle arrest, increased apoptotic cells, depolarized the mitochondrial membrane, and induced morphological alterations in cells and nuclei. It also inhibited A549 cell migration (P < 0.05), colonization, and invasiveness. Moreover, the study demonstrated that R. raetam treatment resulted in the upregulation of Bax expression, downregulation of Bcl-2 expression, and apoptotic fragmented DNA in A549 cells. The top five bioactive compounds derived from R. raetam exhibited molecular interactions that inhibit PIK3CA and AKT1. This inhibition leads to an increased frequency of apoptosis and subsequent death of cancer cells. Additionally, R. raetam extract induced an increase in ROS formation and cytochrome c levels, indicating that its toxic effects on A549 cells involve both ROS-dependent cytotoxicity through the disruption of mitochondrial transmembrane potential ΔΨm and ROS-independent cell cycle arrest through downregulation BCL-2, PARP, E-Cadherin, PI3K, and Akt expressions pathways.

Steroidal constituents in the whole plants of Helleborus niger and their cytotoxic activity in vitro.

Phytochemical investigation of the whole plants of Helleborus niger L. (Ranunculaceae) resulted in the isolation of five undescribed compounds, including one bufadienolide (1), two bufadienolide rhamnosides (2 and 3), and two ecdysteroids (12 and 13), along with eight known compounds (4-11). The chemical structures of 1-3, 12, and 13 were determined by spectroscopic studies, including 2D NMR, and chromatographic and spectroscopic analyses of the hydrolyzed products. Compounds 1-13 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, SBC-3 human small-cell lung cancer cells, and TIG-3 human normal diploid lung cells. Compounds 1-12 showed cytotoxic activity against HL-60, A549, and SBC-3 cells, with IC50 values ranging from 0.0016 to 6.1 µM. Bufadienolide rhamnoside 2 exhibited potent cell proliferation inhibitory activity against SBC-3 cells after 24-48 h of treatment and apoptosis-inducing activity in SBC-3 cells via an intrinsic pathway after 72 h of treatment. The JFCR39 panel screening of 2 suggests that the molecular target of 2 is Na+,K+-ATPase.

Depside and depsidone-rich hydroalcoholic extract, resourced from the lichen Parmelinella wallichiana (Taylor) Elix & Hale selectively restricts Non-Small Cell Lung Cancer by modulating p53, FOXO1 and PALLADIN genes.

The non-specificity of contemporary cancer therapeutics has enticed us to develop safer, anticancer alternatives from natural resources. Lichens are unique natural entities which have long been neglected for explorations in cancer therapy, despite their vast potential. Our present study aims to investigate the anti-cancer potential of a wild lichen Parmelinella wallichiana. The anti-proliferative efficacy of the lichen extracts were screened through MTT assay against a panel of cell lines and the potent hydroalcoholic extract was selected for further evaluation against the most sensitive lung-cancer cell line A549 by implementing a wide range of microscopic and flow cytometric applications. The observations suggest that the extract could selectively induce apoptosis by augmenting ROS and disrupting the mitochondrial membrane potentiality. It was also found that the lichen-induced apoptosis was regulated by two crucial tumor suppressor genes, FOXO1, and p53, along with cell cycle inhibitor p21 which ultimately resulted in robust apoptosis through the up-regulation of pro-apoptotic BAX expression. Moreover, the extract also restricted the cancer progression by down-regulating the PALLADIN expression. Further, an LC-MS-based metabolomic profile highlighted a number of depsides, depsidones and dibenzofurans, which included atranorin, physodalic acid, salazinic acid, constictic acid and usnic acid. Then, an in silico docking with these lichen-derived metabolites against the PI3Kα receptor predicted these compounds has a binding affinity close to a standard PI3Kα inhibitor copanlisib. The study concludes that the extract restricts lung cancer possibly through the PI3Kα/FOXO1 axis and thus Parmelinella wallichiana represents a potential resource for anti-lung cancer drug development in future.

Overcoming obstacles in three-dimensional cell culture model establishment: Approaches for growing A549 non-small cell lung cancer spheroids using a clinostat system.

INTRODUCTION: Non-small cell lung cancer (NSCLC) accounts for 80-85 % of lung cancer cases globally. And the A549 cell line is widely used in pharmacological and toxicity screening. Due to its popularity as a NSCLC model, it was inevitable that three-dimensional (3D) cultures of A549 cells would be established. 3D models increase physiological relevance, and their advanced structure allows researchers to obtain more translatable and reliable results. However, establishing this cell line as a 3D model may come with challenges, like clumping. METHODS: In this study, A549 spheroids were established using a clinostat-based rotating bioreactor system and were characterised in terms of morphology, planimetry, and viability. RESULTS: The main challenge faced included continuous aggregation of the spheroids, which constrained growth and development. This challenge was successfully overcome by supplementation with ascorbic acid, foetal bovine serum coating, and minimising handling, and a NSCLC mini-tumour model was established and semi-characterised. The spheroids survived for 25 days and had a significant increase in growth. CONCLUSION: The A549 spheroid model cultured in a clinostat-based microgravity system was shown to be stable, viable, and suitable to be used in pharmacological and toxicological investigations.

Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway.

Lung cancer has the highest incidence and mortality rates of all cancer types in China and therefore represents a serious threat to human health. In the present study, the mechanism of rabdoternin E against the proliferation of the lung cancer cell line A549 was explored. It was found that rabdoternin E caused the accumulation of large amounts of reactive oxygen species (ROS), promoted cell S phase arrest by reducing the expression of CDK2 and cyclin A2, induced apoptosis by increasing the Bax/Bcl­2 ratio and promoted the phosphorylation of proteins in the ROS/p38 MAPK/JNK signaling pathway, which is associated with apoptosis and ferroptosis. In addition, it was also found that Z­VAD­FMK (an apoptosis inhibitor), ferrostatin­1 (ferroptosis inhibitor) and N­acetylcysteine (a ROS inhibitor) could partially or greatly reverse the cytotoxicity of rabdoternin E to A549 cells. Similarly, NAC (N­acetylcysteine) treatment notably inhibited the rabdoternin E­stimulated p38 MAPK and JNK activation. Furthermore, in vivo experiments in mice revealed that Rabdoternin E markedly reduced tumor volume and weight and regulated the expression levels of apoptosis and ferroptosis­related proteins (including Ki67, Bcl­2, Bax, glutathione peroxidase 4, solute carrier family 7 member 11 and transferrin) in the tumor tissues of mice. Histopathological observation confirmed that the number of tumor cells decreased markedly after administration of rabdoternin E. Taken together, rabdoternin E induced apoptosis and ferroptosis of A549 cells by activating the ROS/p38 MAPK/JNK signaling pathway. Therefore, the results of the present study showed that rabdoternin E is not toxic to MCF­7 cells (normal lung cells), had no significant effect on body weight and was effective and therefore may be a novel therapeutic treatment for lung cancer.

Chemical Composition, Antioxidant Capacity, and Anticancerous Effects against Human Lung Cancer Cells of a Terpenoid-Rich Fraction of Inula viscosa.

Inula viscosa is a widely used plant in traditional Mediterranean and Middle Eastern medicine for various illnesses. I. viscosa has been shown to have anticancer effects against various cancers, but its effects against lung cancer have been under limited investigation. At the same time, I. viscosa is rich in terpenoids whose anti-lung cancer effects have been poorly investigated. This study aimed to examine the potential anticancer properties of methanolic and aqueous extracts of stems and leaves of I. viscosa and its terpenoid-rich fraction against human lung cancer A549 cells. Results showed that the methanolic extracts of I. viscosa had significantly higher polyphenol and flavonoid content and radical scavenging capacity than the aqueous extracts. In addition, leaves methanolic extracts (IVLM) caused the highest reduction in viability of A549 cells among all the extracts. IVLM also reduced the viability of human ovarian SK-OV-3, breast MCF-7, liver HepG2, and colorectal HCT116 cancer cells. A terpenoid-rich I. viscosa fraction (IVL DCM), prepared by liquid-liquid separation of IVLM in dichloromethane (DCM), displayed a substantial reduction in the viability of A549 cells (IC50 = 27.8 ± 1.5 µg/mL at 48 h) and the panel of tested cancerous cell lines but was not cytotoxic to normal human embryonic fibroblasts (HDFn). The assessment of IVL DCM phytochemical constituents using GC-MS analysis revealed 21 metabolites, highlighting an enrichment in terpenoids, such as lupeol and its derivatives, caryophyllene oxide, betulin, and isopulegol, known to exhibit proapoptotic and antimetastatic functions. IVL DCM also showed robust antioxidant capacity and decent polyphenol and flavonoid contents. Furthermore, Western blotting analysis indicated that IVL DCM reduced proliferation (reduction of proliferation marker Ki67 and induction of proliferation inhibitor proteins P21 and P27), contaminant with P38 MAP kinase activation, and induced the intrinsic apoptotic pathway (P53/BCL2/BAX/Caspase3/PARP) in A549 cells. IVL DCM also reduced the migration of A549 cells, potentially by reducing FAK activation. Future identification of anticancer metabolites of IVL DCM, especially terpenoids, is recommended. These data place I. viscosa as a new resource of herbal anticancer agents.

Cytotoxic and antibacterial compounds from Schinus terebinthifolia Raddi fruits.

Chromatographic procedures of extracts of Schinus terebinthifolia Raddi fruits afforded (Z)-masticadienoic (1) and 3ß-masticadienolic (2) acids, tetrahydroamentoflavone (3), and 4-O-methyl gallic acid (4). Addicionally, the derivative 6-oxo masticadienoic acid (1a) was prepared by an allylic oxidation. The chemical structures of obtained compounds were elucidated by spectrometric data analyses. Furthermore, both the semi-synthetic derivative and the metabolites were subjected to in vitro cytotoxicity against the A549 human lung cancer cell line, as well as antimicrobial activity tests. Compounds 2 and 1a exhibited cytotoxicity towards A549 cells with IC50 values of 20.13 and 6.11 µM, respectively. In the tests against pathogens, the CHCl3 and EtOAc soluble fractions of MeOH extract along with the pure compounds, exhibited antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Except for 4-O-methyl gallic acid, the other pure compounds showed inhibitory microbial activities with MIC values ranging from 0.25 µg/mL to 25 µg/mL doses.

The anticancer mechanisms of Toxoplasma gondii rhoptry protein 16 on lung adenocarcinoma cells.

Lung adenocarcinoma is the most prevalent subtype of lung cancer, which is the leading cause of cancer-related mortality worldwide. Toxoplasma gondii (T.gondii) Rhoptry protein 16 (ROP16) has been shown to quickly enter the nucleus, and through activate host cell signaling pathways by phosphorylation STAT3 and may affect the survival of tumor cells. This study constructed recombinant lentiviral expression vector of T. gondii ROP16 I/II/III and stably transfected them into A549 cells, and the effects of ROP16 on cell proliferation, cell cycle, apoptosis, invasion, and migration of A549 cells were explored by utilizing CCK-8, flow cytometry, qPCR, Western blotting, TUNEL, Transwell assay, and cell scratch assay, and these effects were confirmed in the primary human lung adenocarcinoma cells from postoperative cancer tissues of patients. The type I and III ROP16 activate STAT3 and inhibited A549 cell proliferation, regulated the expression of p21, CDK6, CyclinD1, and induced cell cycle arrest at the G1 phase. ROP16 also regulated the Bax, Bcl-2, p53, cleaved-Caspase3, and Caspase9, inducing cell apoptosis, and reduced the invasion and migration of A549 cells, while type II ROP16 protein had no such effect. Furthermore, in the regulation of ROP16 on primary lung adenocarcinoma cells, type I and III ROP16 showed the same anticancer potential. These findings confirmed the anti-lung adenocarcinoma effect of type I and III ROP16, offering fresh perspectives on the possible application of ROP16 as a target with adjuvant therapy for lung adenocarcinoma and propelling the field of precision therapy research toward parasite treatment of tumors.

Astragalus Polysaccharides and Metformin May Have Synergistic Effects on the Apoptosis and Ferroptosis of Lung Adenocarcinoma A549 Cells.

Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin on apoptosis and ferroptosis were compared. Furthermore, the combination treatment of APS and metformin was also investigated. We found that APS not only reduced the growth of lung cancer cells but also had a synergistic effect with metformin on A549 cells. The study results showed that it may be promising to use APS and metformin as a combination therapy for the treatment of lung adenocarcinoma.

Fractionated Leaf Extracts of Ocimum gratissimum Inhibit the Proliferation and Induce Apoptosis of A549 Lung Adenocarcinoma Cells.

Previous in vitro studies in our laboratory demonstrated that ethyl acetate (P2) and water- soluble (PS/PT1) fractionated leaf extracts of Ocimum gratissimum inhibit the proliferation of prostate cancer cells. It has been reported that the crude aqueous extract induces apoptosis in lung adenocarcinoma cells; however, the efficacy of the fractionated extracts against these cells remains unclear. In the present study, we hypothesized that the ability of the fractionated extracts to inhibit proliferation and induce apoptosis is associated with the activation of pro-apoptotic proteins and induction of DNA condensation in A549 cells. Ocimum gratissimum was cultivated and its leaves were harvested, extracted, and fractionated to produce fractions P2 and PS/PT1. Anti-proliferative activity was assessed by direct cell count. For morphological characterization of apoptosis, 4',6-diamidino-2-phenylindole staining was employed. Western blot analysis was performed to evaluate the apoptotic activity of the fractionated extracts. In data generated from anti-proliferation studies, P2 significantly inhibited cell proliferation in a concentration-dependent manner; PS/PT1 elicited a decrease in the viability of cells, occurring at 500 µg/mL. 4',6-diamidino-2-phenylindole staining revealed the induction of apoptosis, as evidenced by the formation of apoptotic bodies. Increased levels of pro-apoptotic proteins were observed as the concentrations of the fractionated extracts increased. These results suggest that fractionated leaf extracts of Ocimum gratissimum inhibit the proliferation and induce apoptosis of A549 cells.

Chrysin-functionalized gold nanoparticles and paclitaxel exhibit synergistic impact on lung cancer cell lines via regulating the AKT/PPAR-ϒ/ß-catenin pathway.

Lung cancer has become progressively widespread, posing a challenge to traditional chemotherapeutic drugs such as platinum compounds and paclitaxel (PTX) owing to growing resistance. Along with that, the chemotherapeutic drugs infer major side effects. The usage of natural compounds as chemosensitizers to boost the efficacy of these chemotherapeutic drugs and minimizing their toxicity is a plausible approach. In our investigation, we employed PTX as the standard chemotherapeutic agent and utilized chrysin-functionalized gold nanoparticles (CHR-AuNPs) to augment its cytotoxicity. Gold nanoparticles were chosen for their inherent cytotoxic properties and ability to enhance chrysin's bioavailability and solubility. Characterization of CHR-AuNP revealed spherical nanoparticles within the nano-size range (35-70 nm) with a stable negative zeta potential of -22 mV, confirmed by physicochemical analyses including UV-visible spectroscopy, Fourier transform infrared (FTIR) spectral analysis, and visual observation of the wine-red coloration. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay cytotoxicity studies demonstrated CHR-AuNP's superior efficacy compared to CHR alone, with synergistic effects observed in combination with PTX, validated by Compusyn software. Morphological changes indicative of apoptosis were more pronounced with combined treatment, corroborated by acridine orange/ethidium bromide (AO/EtBr) staining and Annexin V assays. Furthermore, the combination treatment amplified reactive oxygen species (ROS) production and destabilized mitochondrial membrane potential, while altering the expression of pro-apoptotic and anti-apoptotic proteins. Exploring the mechanistic pathways, we found that the drugs upregulated PPAR-γ expression while suppressing Akt and overexpressing PTEN, thereby impeding the Wnt/ß-catenin pathway commonly dysregulated in lung cancer. This highlights the potential of low-dose combination therapy with PTX and CHR-AuNP as a promising strategy for addressing lung cancer's challenges.

Preparation of Biomimetic Selenium-Baicalein Nanoparticles and Their Targeted Therapeutic Application in Nonsmall Cell Lung Cancer.

In this study, we prepared bionic selenium-baicalein nanoparticles (ACM-SSe-BE) for the targeted treatment of nonsmall cell lung cancer. Due to the coating of the A549 membrane, the system has homologous targeting capabilities, allowing for the preparation of target tumor cells. The borate ester bond between selenium nanoparticles (SSe) and baicalein (BE) is pH-sensitive and can break under acidic conditions in the tumor microenvironment to achieve the targeted release of BE at the tumor site. Moreover, SSe further enhances the antitumor effect of BE by increasing the production of ROS in tumor cells. Transmission electron microscopy (TEM) images and dynamic light scattering (DLS) showed that the ACM-SSe-BE had a particle size of approximately 155 ± 2 nm. FTIR verified the successful coupling of SSe and BE. In vitro release experiments indicated that the cumulative release of ACM-SSe-BE at pH 5.5 after 24 h was 69.39 ± 1.07%, which was less than the 20% release at pH 7.4, confirming the pH-sensitive release of BE in ACM-SSe-BE. Cell uptake experiments and in vivo imaging showed that ACM-SSe-BE had good targeting ability. The results of MTT, flow cytometry, Western blot, and cell immunofluorescence staining demonstrated that ACM-SSe-BE promoted A549 cell apoptosis and inhibited cell proliferation. The in vivo antitumor results were consistent with those of the cell experiments. These results clearly suggested that ACM-SSe-BE will be a promising bionic nanosystem for the treatment of nonsmall cell lung cancer.

Engineering aptamers to enhance their interaction with protein target for selective inhibition of cell surface receptors.

Cell surface receptors play a key role in intracellular signaling, and their overexpression and activation are among the drivers of multiple diseases. Selective inhibition of cell surface receptors is important for regulating intracellular signaling pathways and cell behavior. Here, we design engineered aptamers to selectively inhibit receptor function. In this strategy, the aptamer specifically recognizing the extracellular structural domain of the EGFR, was conjugated to an adamantane moiety through linking arms of various lengths in order to obtain better performances toward EGFR. These interactions inhibit EGFR dimerization, thereby impeding the activation of downstream signaling pathways. It is shown that the adamantane-modified aptamers exhibit superior inhibition of downstream effector proteins relative to the unmodified aptamers. The optimal inhibitory effect was observed with a linker arm of 40 T-base in length. Notably, the best-performing adamantane-modified aptamer specifically binds to A549 cells with a dissociation constant (22.6 ± 4.5 nM) that is approximately 4-fold lower than that of the parent EGFR aptamer (94.4 ± 21.9 nM). We further combine the use of the adamantane-modified aptamer with that of genistein, a natural isoflavone compound with EGFR tyrosine kinase inhibition activity, to enhance the inhibitory effect on EGFR and its downstream signaling employing a synergistic action. This study is expected to provide a versatile approach for the improvement of existing aptamers obtaining increased selective inhibition of cell surface receptors.