Growth Of A549 Research Articles

Exploring the anti-NSCLC mechanism of phillyrin targeting inhibition of theHSP90-AKT pathway.

Phillyrin (PHN), derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a kind of Chinese herbal medicine with the effect of clearing heat, and has been used in China for thousands of years in treating various tumors. However, the mechanism of its main components on non-small cell lung cancer (NSCLC) remains unclear. PHN is a distinct component extracted from Forsythia suspensa with promising anti-cancer activity against various tumor types. This study sought to elucidate the promising effects of PHN on NSCLC. Based on network pharmacology results, we identified potential PHN targets and pathways for NSCLC treatment. CCK-8 assay, wound healing assay, apoptosis assay, western blot, and in vivo experiments verified the inhibitory effect of PHN on NSCLC. Network pharmacology identified 160 potential PHN targets, 955 NSCLC-related targets, and 54 common targets, along with 132 pathways and 2 core genes. Biological experiments demonstrated that PHN significantly inhibited the growth and migration of A549 and LLC cells while promoting their apoptosis. Western blot analysis revealed down-regulation of AKT, HSP90AA1, and CDC37 expression, suggesting that PHN inhibits A549 and LLC cell proliferation by down-regulating the HSP90-AKT pathway. In vivo experiments confirmed that PHN significantly inhibited NSCLC growth with low toxicity. This study, using network pharmacology and biological experiments, verified the effectiveness of PHN against NSCLC through the HSP90-AKT pathway. These findings provide a foundation for further research and analysis.

Synthesis, characterization and anticancer, antibacterial activities of pentacyclic triterpenoid glycoside derivatives

As a kind of glycoside, pentacyclic triterpenoid saponins have good biological activities, such as anticancer, antibacterial, antiviral and hypoglycemic effects [1]. In this paper, twenty-four pentacyclic triterpenoid derivatives, including twelve monosaccharide derivatives, were designed and synthesized. The anticancer effect and antibacterial activities of all compounds were evaluated. It is noteworthy that compound UA-2b has the strongest inhibitory effect on the growth of A549, Hela and HepG2 cancer cells (IC50 = 5.37 ± 0.22 µM, 5.82 ± 0.25 µM and 5.47 ± 0.06 µM, respectively). Compounds OA-2b, OA-6a, OA-6b, UA-2b and UA-6a have the best activity against Escherichia coli 1924 (MIC = 16 μg/ml).

Novel tris-bipyridine based Ru(II) complexes as type-I/-II photosensitizers for antitumor photodynamic therapy through ferroptosis and immunogenic cell death

Ru(II) complexes have attracted attention as photosensitizers for their promising photodynamic properties. Herein, novel tris-bipyridine based Ru(II) complexes (6a-e) were synthesized by introducing saturated heterocycles to improve photodynamic properties and lipid-water partition coefficients. Among them, 6d demonstrated significant phototoxicity towards three cancer cells, with IC50 values of 5.66–7.17 μM, exceeding values in dark (IC50s > 100 μM). Under hypoxic conditions, 6d maintained excellent photodynamic activity in A549 cells, with PI values exceeding 24, highlighting its potential for highly effective type-I/-II photodynamic therapy by inducing ROS generation, oxidative stress, and mitochondrial damage. Additionally, it induced ferroptosis and immunogenic cell death of A549 cells by regulating the expression of relevant markers. Finally, 6d remarkably inhibited the growth of A549 transplanted tumor growth by 95.4 %. This Ru(II) complex shows great potential for cancer treatment with its potent photodynamic activity and diverse mechanisms of tumor cell death.

Antioxidant properties and bioactivity of three marine microalgae on human cancer cell lines

ABSTRACT Marine microalgae offer significant potential as sustainably cultivable microorganisms for the biorefining of a diverse array of functional metabolites. In this study, three species of marine microalgae, Tetraselmis chuii Butcher CCAP 66/21B (Chlorophyte), Phaeodactylum tricornutum Bohlin CCAP 1052/1 (Diatom) and Amphidinium carterae Hulburt CCAP 1102/8 (Dinoflagellate), were batch cultivated and their biomass retrieved for analysis in terms of pigment and fatty acid composition as well as bioactivity potential. Sequential solvent maceration of the biomass returned extracts was used to determine antioxidant capacity and assess their growth inhibition potential against A549 (a human lung carcinoma) and MCF-7 (a breast carcinoma) cell lines. The extracts of A. carterae showed higher antioxidant capacity (≤ 33.5 μmol Trolox Equivalent mg Recovered Dried Material‒1) compared to the other extracts. No major cytotoxic activity nor production of reactive oxygen species was observed using the extracts of T. chuii and P. tricornutum. However, the methanolic extraction of A. carterae inhibited the growth of both A549 and MCF-7 cells (< 4%) at 25, 50 and 100 µg ml−1 concentrations, as determined using the MTS assay and AO/PI cell staining. Microalgal metabolites have the potential for practical applications in a variety of industrial sectors. The absence of toxicity and substantial antioxidant potential of extracts of T. chuii and P. tricornutum confirm their suitability for incorporation into animal feeds or human nutrition supplements. A. carterae also appears to be a promising source of bioactives that can be further valorized via multi-compound biorefinery pipelines.

Metabolomic insights and bioactive efficacies of Tragopogon dubius root fractions: Antioxidant and antiproliferative assessments

Tragopogon dubius is commonly consumed as a vegetable and used in traditional medicine for treating inflammatory skin conditions and cutaneous swelling. Despite known pharmacological properties of its leaves and roots, many of its biological characteristics and active phytochemicals remain unexplored. The present study investigates the phytochemical composition, antioxidant, and anticancer properties of methanolic root extracts and isolated fractions (TdRM-1 and TdRM-2) of T. dubius. Utilizing preparative thin-layer chromatography, the crude extract was successfully separated into TdRM-1 and TdRM-2, characterized by GC-MS and FTIR analysis, revealing a diverse range of bioactive compounds including terpenes, flavonoids, and phenolic acids. Qualitative phytochemical screening indicated the presence of carbohydrates, tannins, alkaloids, and other phytoconstituents. Advanced UPLC-ESI-QTOF-MS analysis identified 54 metabolites, significantly contributing to the chemical profiling of the extract. The antioxidant activities of the fractions were quantitatively assessed using ABTS, DPPH, and superoxide radical scavenging assays, where TdRM-2 exhibited superior activity with IC50 values ranging from 51.29 to 60.03 μg/mL. Anticancer potential was evaluated against A549, LN-18, and MCF-7 cancer cell lines, demonstrating that TdRM-2 significantly inhibited cell proliferation with GI50 values as low as 31.62 μg/mL for A549 cells. Additionally, fluorescence microscopy revealed that TdRM-2 induces apoptosis, indicated by changes in nuclear morphology and loss of mitochondrial membrane potential. Annexin V-FITC/PI double staining indicate that the TdRM-2 fractions from T. dubius can significantly inhibit the growth of A-549, LN-18, and MCF-7 cancer cell lines by inducing apoptosis These findings suggest that T. dubius root extracts, particularly the TdRM-2 fraction, hold promising therapeutic potential due to their significant antioxidant and anticancer activities, underpinned by their rich phytochemical composition. This study underscores the importance of T. dubius as a source of natural bioactive compounds with potential health benefits.

Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms. The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model. The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and β-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3β at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction. The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

Review of Sacred Herbal Medicine Aegle marmelos: A Potent Metastasis Inhibitor

Abstract: Aegle marmelos (A. marmelos) appears to be a significantly used ayurvedic medicine. This is a brilliantly composed nutritious fruit with carbohydrates, proteins, vitamins like riboflavin, thiamine, niacin, fatty acids, and minerals. Scientific studies have proved that A. marmelos has phytochemicals: carotenoids, phenolic, alkaloids, pectins, tannins, coumarins, flavonoids and terpenoids. Recent research on the effects of A. marmelos proved its anticancer, antimicrobial, cardioprotective, antidiabetic, and hepatoprotective activities. Extracts of various parts of plants such as leaves, bark, stems, fruits, and pulp subjected to preclinical studies conducted on cell lines showed apoptosis induction, inhibition of cell cycle and inhibition of proliferation of cells. Anti-cancer activity of A. marmelos was studied on selected cell lines of lung cancer, breast cancer, colon cancer and leukaemia. A. marmelos reported significant inhibitory effect on cell proliferation in cell line studies on A549, Ehrlich Ascites Carcinoma, MNU, DMBA, MCF-7, k562 cells, t-lymphoid Jurkat cells, b lymphoid Raji cells, erythroleukemic Hel cells, melanoma Colo 38 cells which supports the anticancer potential of it. Imperatorin has shown an antiproliferative effect on several cancer cell lines. The hydroethanolic extract of A. marmelos leaves showed a decrease in cell viability on A549 Human lung cancer cell line which works by fold change over control of the β-Catenin-m RNA and Wnt-mRNA expression of A549 and tumour growth suppression in DMBA induced carcinogenesis in rats. In human promyelocytic leukaemia, HL-60 cells, imperatorin from A. marmelos has caused cytochrome c-dependent apoptosis. Drugs interfere with the proliferative and survival signals that suppress the growth of K562 cells by blocking BCR-ABL1. Proper awareness, development of formulation and consumption of it make this drug scale up commercially.

Abstract 3273: Tirapazamine sensitizes homologous recombination-proficient cancers by enhancing DNA damage andferroptosis

Abstract Despite its success in HR-deficient tumors, the application of PARP inhibitors (PARPis) in HR-proficient cancers is very limited. Since the majority of cancers are HR-proficient, there is a need for developing strategies to extend the use of PARPis to HR-proficient cancers. We investigated whether the hypoxic cytotoxin, tirapazamine (TPZ) sensitizes HR-proficient cancer cells to PARPis under normoxia and hypoxia (2% O2), and found that TPZ enhanced PARPi cell killing to a greater extent under hypoxia compared to normoxia. Mechanistically, this enhanced killing was due to the induction of DNA double-strand breaks and free radicals that lead to ferroptotic cell death. To determine the role of hypoxia in the anti-tumor effect of the combination treatment, we examined the efficacy of TPZ and PARPi treatment in hypoxic spheroids and subcutaneous xenograft models derived from a panel of HR-proficient human non-small cell lung cancer (NSCLC) cells. We found that PARPis combined with TPZ significantly inhibited the growth of the hypoxic NSCLC spheroids. In addition, the combination treatment significantly inhibited the growth of A549 and CORL105 xenografts that possess significant hypoxic fractions, but did not significantly inhibit the growth of well-oxygenated Calu3 and H3122 xenografts. Taken together, this study demonstrates that TPZ can sensitize HR-proficient tumor cells to PARPi through the introduction of DNA strand breaks and free radicals, suggesting that TPZ treatment can broaden the usage of PARPi to HR-proficient cancers. Citation Format: Yanyan Jiang, Hala Estephan, Yizhou Wang, Ftoon Aljarbou, Nuria V. Lopera, Eui Jung Moon, Ester M. Hammond, Amato J. Giaccia. Tirapazamine sensitizes homologous recombination-proficient cancers by enhancing DNA damage andferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3273.

Identification and functional analysis of phycocyanin-derived bioactive peptides with non-small cell lung cancer cell inhibition

Non-small cell lung cancer (NSCLC) is one of the most lethal types of malignancies around the world. Phycocyanin, a type of functional food additive derived from photosynthetic pigment protein in Spirulina cells, has been verified to exhibit antineoplastic effect on NSCLC. However, the investigation on bioactive peptides of phycocyanin, especially in NSCLC, remains poorly documented. The goal of this work is to identify novel phycocyanin-derived bioactive peptides with NSCLC cell inhibition function. Phycocyanin was hydrolysed by trypsin, followed by peptides isolation, purification and identification through ultrafiltration, high performance liquid chromatography (HPLC) and mass spectrometry (MS), respectively. Three phycocyanin peptides (PCP1: AGDASVLEDR, PCP2: ADSLLSGLR and PCP3: MFDAFTK) predicted to exhibiting anticancer ability were identified. Molecular docking analysis indicated the peptides had strong interaction with epidermal growth factor receptor (EGFR), a proto-oncogene in cells. Phenotype experiments showed that peptides significantly inhibited growth and migration of A549, H1299 and LTEP-a2 cells. Moreover, they also suppressed the activity of Akt pathway of NSCLC cells. Three phycocyanin-derived peptides might be suitable for development as new anti-lung cancer agents, owing to their antineoplastic activities. The current work also provides a vital basis for further utilization of marine algae nutrient components.

Synthesis, Biological Investigation, and Molecular Docking of Novel Benzimidazole‐Hydrazone Hybrids as Potential Anticancer Agent Candidates

AbstractIn this study, six novel Benzimidazole‐hydrazone derivatives starting from the commercially available 1H‐benzo[d]imidazole‐2‐amine were synthesized, and the molecular structure of the obtained compounds were confirmed by NMR, FTIR and MS spectroscopic techniques. The anticancer activities of the synthesized compounds were investigated against HT29 (Human colon adenocarcinoma) and A549 (Human non‐small cell lung cancer) cancer cell lines using xCELLigence real‐time cell analysis. Cell apoptosis was determined by DNA laddering assay and Annexin V/FITC flow cytometer. Compound 4 c exhibited the best anticancer potency against both cancer cell lines (A549 and HT29) with IC50 values of 0.0019 μM and 0.0093 μM, respectively. Compound 4 c reduced the growth of A549 and HT29 cells in vitro and induced early apoptosis of A549 and HT29 cells. Additionaly, all compounds demonstrated favorable pharmacokinetics properties compared to Paclitaxel (reference compound) and the best docking scores were obtained for compounds 4 e and 4 b among the compounds.

Novel tetrahydroisoquinolines as DHFR and CDK2 inhibitors: synthesis, characterization, anticancer activity and antioxidant properties

In this study, we synthesized new 5,6,7,8-tetrahydroisoquinolines and 6,7,8,9-tetrahydrothieno[2,3-c]isoquinolines based on 4-(N,N-dimethylamino)phenyl moiety as expected anticancer and/or antioxidant agents. The structure of all synthesized compounds were confirmed by spectral date (FT-IR, 1H NMR, 13C NMR) and elemental analysis. We evaluated the anticancer activity of these compounds toward two cell lines: A459 cell line (lung cancer cells) and MCF7 cell line (breast cancer cells). All tested compounds showed moderate to strong anti-cancer activity towards the two cell lines. Compound 7e exhibited the most potent cytotoxic activity against A549 cell line (IC50: 0.155 µM) while compound 8d showed the most potent one against MCF7 cell line (IC50: 0.170 µM) in comparison with doxorubicin. In addition, we examined the effect of compounds 7e and 8d regarding the growth of A549 and MCF7 cell lines, employing flow cytometry and Annexin V-FITC apoptotic assay. Our results showed that compound 7e caused cell cycle arrest at the G2/M phase with a 79-fold increase in apoptosis of A459 cell line. Moreover, compound 8d caused cell cycle arrest at the S phase with a 69-fold increase in apoptosis of MCF7 cell line. Furthermore, we studied the activity of these compounds as enzyme inhibitors against several enzymes. Our findings by docking and experimental studies that compound 7e is a potent CDK2 inhibitor with IC50 of 0.149 µM, compared to the Roscovitine control drug with IC50 of 0.380 µM. We also found that compound 8d is a significant DHFR inhibitor with an IC50 of 0.199 µM, compared to Methotrexate control drug with IC50 of 0.131 µM. Evaluation of the antioxidant properties of ten compounds was also studied in comparison with Vitamin C. Compounds 1, 3, 6, 7c and 8e have higher antioxidant activity than Vitamin C which mean that these compounds can used as potent antioxidant drugs.Graphical

The Investigation of Quercus Infectoria Gall Aqueous Extract Effect on the Cell Proliferation, Apoptosis and Expression of CCND1, TP53, BCL2 and BAX Genes in Cell Line of Lung, Gastric and Esophageal Cancers.

The therapeutic potential of Quercus infectoria (QI) gall, including its anti-inflammatory, antioxidant, and anticancer properties, is well-known. However, its impact on lung, gastric, and esophageal cancer cells remain unclear. This study aims to explore the effects of QI gall aqueous extract on cell viability, apoptosis, and gene expression in A549, BGC823, and KYSE-30 cell lines. A549, BGC823, and KYSE-30 cells were seeded in complete medium and incubated with different concentrations of QI gall extract for 24 hours. Cell viability was measured by an MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The induction of apoptosis was assessed through flow cytometric analysis after the adding FITC-conjugated Annexin V (Annexin V-FITC) and propidium iodide (PI). The mRNA expression levels of CCND1, TP53, BCL2 and BAX genes were determined using Real-time Quantitative Polymerase Chain Reaction analysis. The MTT assay demonstrated that treatment with QI gall extract significantly reduced the number of viable cells in the A549, BGC823, and KYSE-30 cell lines at IC50 concentrations of 440.1, 437.1, and 465.2 mg/ml, respectively. Additionally, compared to untreated cell population, the percentages of early apoptosis, late apoptosis, and necrosis in the A549, BGC823, and KYSE-30 cells significantly increased following treatment with QI gall extract (P< 0.05). Also, the treatment with QI gall extract influenced the expression of CCND1, TP53, BCL2 and BAX genes. The present findings indicated that the gall extract of QI can inhibit the growth of A549, BGC823, and KYSE-30 cells by inducing apoptosis, which may be mediated via mitochondria-dependent pathway.

Targeted therapies for breast and lung cancers by using Propolis loaded albumin protein nanoparticles

BackgroundCancer is a popular disease among many others that can threaten human life. This is not only because of its invasiveness but also because of its resistance and the highly effective cost of its treatments. Propolis is rich in natural bioactive and polyphenolic compounds that have proven their strong effect on cancer cells such as MCF-7 and A549 cell lines. MethodsPropolis extract was immobilized into the bovine serum albumin (BSA) conjugated to folic acid (FA), to increase control of its delivery and to strengthen its cellular uptake. ResultsThe growth of MCF-7 was significantly decreased by propolis extract and BSA-propolis NPs after their incubation for 48 and 72 h by (54 ± 0.01 %, and 45 ± 0.005 %, P ≤ 0.001) and (20 ± 0.01 % and 10 ± 0.005 %, P ≤ 0.0001), respectively. Similarly, there is a significant inhibition in the growth of A549 obtained after their incubation with (propolis extract and albumin-propolis NPs) for 72 h (15 ± 0.03 % and 5 ± 0.01 %, P ≤ 0.00001). Propolis extract and BSA-propolis NPs exhibited a greater effect on protein expression of MCF-7 and A549, showing significant modulation of caspase-3, cyclin D1, and light chain 3 (LC3II). The result was supported by nuclear fragmentations and activation of acidic/neutral autophagosomes in acridine orange/ethidium bromide (AO/EB) and 4′,6-diamidino-2-phenylindole (DAPI) nuclear stains. According to this study, the expression of phospho-GSK3β (Ser9) (p < 0.001) increased significantly in MCF-7 and A549 cells after their exposure to propolis extract and BSA-propolis NPs. ConclusionResults support the potency application of propolis and its encapsulation as an alternative therapeutic agent for cancer treatments instead of chemotherapies because of its action on multi-signaling pathways.

Unveiling the oncogenic significance of thymidylate synthase in human cancers.

Thymidylate synthase (TYMS) constitutes a pivotal and potent target in the context of chemoresistance. However, the oncogenic role of TYMS has received insufficient attention. Leveraging data from the Cancer Genome Atlas (TCGA) and various public databases, we conducted an extensive investigation into the oncogenic role of TYMS across 33 cancer types. Subsequently, TYMS was inhibited using small interfering RNA (siRNA) in four different cell lines, and cell proliferation and migration were assessed using CellTiter-Glo and Transwell assays. TYMS exhibited pronounced expression across a spectrum of cancers and demonstrated associations with clinical outcome in diverse cancer patient cohorts. Furthermore, genetic alterations were identified as potential influencers of overall survival in specific tumor types. Notably, the expression of thymidylate synthase correlated with tumor-infiltrating CD4+ cells in select cancers. Additionally, the functional mechanism of TYMS encompassed nucleotidase activity, chromosome segregation, and DNA replication progress. In vitro experiments further substantiated these findings, demonstrating that the suppression of TYMS impeded the cell growth and invasive capabilities of HeLa, A549, 786-O, and U87_MG cells. This study furnishes a comprehensive understanding of the oncogenic role played by TYMS in human tumors.

α-Conotoxin recombinant protein ImI-AFP3 efficiently inhibits the growth and migration of lung cancer cells

α-Conotoxin ImI is a selective antagonist of alpha7 nicotinic acetylcholine receptor (α7 nAChR) that is involved in cancer development. Human alpha fetoprotein domain 3 (AFP3) is a prototype of anticancer agents. In an effort to design drugs for anticancer treatments, we fused the ImI peptide to AFP3 as a fusion protein for testing. The fusion protein (ImI-AFP3) was highly expressed in the insect Bac-to-Bac system. The purified fusion protein was found to have improved anticancer activity and synergized with the drug gefitinib to inhibit the growth and migration of A549 and NCI-H1299 lung cancer cells. Our data have demonstrated that the recombinant protein ImI-AFP3 is a promising candidate for drug development to suppress lung cancer cell growth, especially to suppress hepatoid adenocarcinoma of the lung (HAL) cell growth.

Benzylisoquinoline alkaloids with their antitumor activity from the aerial parts of Corydalis impatiens (pall.) Fisch

Phytochemical investigation on the aerial parts of Corydalis impatiens (pall.) Fisch (Papaveraceae) resulted in the identification of four previous undescribed benzylisoquinoline alkaloids, impatienines A-D (1–4), together with 14 known analogues (5–18). The structures of these compounds were elucidated by extensive spectroscopic analysis (IR, HR-ESIMS, 1D- and 2D-NMR) as well as ECD calculations. All the compounds obtained were investigated for their inhibitory effect on the growth of A549, H1299 and HepG2 cancer cells. Compounds 7 and 15 exhibited pronounced inhibition against the A549 cancer cells with IC50 values of 6.81 μM and 3.17 μM, while the positive control cisplatin was 1.83 μM. Compounds 1–3 showed moderate inhibitory on the H1299 cancer cells. Compounds 4, 10–12, and 16 showed signiffcant activity against HepG2 cancer cells with IC50 values range of 4.41–8.75 μM.

Preparation and photothermal therapy of gold nanorods modified by Belamcanda chinensis (L.) DC polysaccharide

In recent years, the application of nanoparticles formed by coupling metal nanomaterials of photothermal therapy with polysaccharides as modified carriers in the targeted treatment of liver cancer has attracted extensive attention. In the present work, an undescribed homogeneous polysaccharide BCP50–2 was obtained from Belamcanda chinensis (L.) DC. The structural analysis displayed that BCP50–2 contained galactose and a small amount of arabinose, and was mainly composed of six monosaccharide residues: →3,5)-α-l-Araf-(1→, →4)-β-d-Galp-(1→, →4,6)-β-d-Galp-(1→, →3)-α-l-Galp-(1→, terminal α-l-Araf, and terminal β-d-Galp. To enhance the antitumor activity of BCP50–2, BCP50–2-AuNRs were prepared by coupling BCP50–2 with gold nanorods for the treatment of liver cancer. BCP50–2-AuNRs were rod-shaped with a long diameter of 26.8 nm and had good photothermal conversion effects. Under near-infrared (NIR) light irradiation, BCP50–2-AuNRs possessed photothermal effects and suppressed the growth of HepG2, A549, and MCF-7 cells. In addition, BCP50–2-AuNRs inhibited the development of liver cancer by inducing cell apoptosis, arresting the cell cycle in G2/M phases, and inhibiting cell migration. Moreover, BCP50–2-AuNRs inhibited tumor proliferation, migration, and angiogenesis in zebrafish. In summary, BCP50–2-AuNRs may be potentially useful for cancer treatment.

Conditioned media of tonsil derived mesenchymal stem cells shows different rates of cytotoxicity on solid cancer cells

Aims: Mesenchymal stem cells (MSCs) are the apple of the eye of cancer studies. It was indicated that the secreted factors, especially released by MSCs, have tumoral or anti-tumoral effects on tumor progression. MSCs obtained from different sources show different anti-tumoral effects, while MSCs originating from the same source also show different tumoral effects in different cancer cells. Here, we investigated the anti-tumor effects of soluble factors secreted from palatine tonsil MSCs (TMSC) as a new source of MSC on human lung carcinoma (A549) and pancreatic cancer (PANC-1) cell lines.&#x0D; Methods: Conditioned medium (CM) was obtained from TMSCs isolated from palatine tonsil tissue, and the cytotoxic effect of CM on the growth of A549 and PANC-1 in a dose-dependent manner was demonstrated by MTT analysis. In addition, the function of CM treatment on the cell cycle status of cancer cells and the apoptosis process were investigated through cell cycle analysis with propidium iodide (PI) and Annexin-V/PI detection method by flow cytometry analysis, respectively. &#x0D; Results: We demonstrated that TMSC-CM treatment significantly decreased the viability of A549 and PANC-1 cell lines in a dose-dependent manner post-48 hours. In addition, CM treatment differentially induced the apoptosis on A549 and PANC-1 cells and also, caused G2/M arrest in the cells.&#x0D; Conclusion: In light of these findings, our study is the first to show that TMSC-CM has an anti-tumoral effect by stimulating apoptosis on A549 and PANC-1 cells. These findings reveal that the usage of CM has a cell-free cellular therapeutic potential.

Ebselen Inhibits the Growth of Lung Cancer Cells via Cell Cycle Arrest and Cell Death Accompanied by Glutathione Depletion.

Ebselen is a glutathione (GSH) peroxidase (GPx) mimic originally developed to reduce reactive oxygen species (ROS). However, little is known about its cytotoxicological effects on lung cells. Therefore, this study aimed to investigate the effects of Ebselen on the cell growth and cell death of A549 lung cancer cells, Calu-6 lung cancer cells, and primary normal human pulmonary fibroblast (HPF) cells in relation to redox status. The results showed that Ebselen inhibited the growth of A549, Calu-6, and HPF cells with IC50 values of approximately 12.5 μM, 10 μM, and 20 μM, respectively, at 24 h. After exposure to 15 μM Ebselen, the proportions of annexin V-positive cells were approximately 25%, 65%, and 10% in A549, Calu-6, and HPF cells, respectively. In addition, Ebselen induced arrest at the S phase of the cell cycle in A549 cells and induced G2/M phase arrest in Calu-6 cells. Treatment with Ebselen induced mitochondrial membrane potential (MMP; ΔΨm) loss in A549 and Calu-6 cells. Z-VAD, a pan-caspase inhibitor, did not decrease the number of annexin V-positive cells in Ebselen-treated A549 and Calu-6 cells. Intracellular ROS levels were not significantly changed in the Ebselen-treated cancer cells at 24 h, but GSH depletion was efficiently induced in these cells. Z-VAD did not affect ROS levels or GSH depletion in Ebselen-treated A549 or Ebselen-treated Calu-6 cells. In conclusion, Ebselen inhibited the growth of lung cancer and normal fibroblast cells and induced cell cycle arrest and cell death in lung cancer cells with GSH depletion.

Anti-proliferative activity, molecular genetics, docking analysis, and computational calculations of uracil cellulosic aldehyde derivatives

In this study, the oxidation of microcrystalline cellulose using NaIO4 to yield the corresponding cellulose aldehyde utilized microwave irradiation as a green tool, the obtained cellulosic aldehyde was confirmed through spectral analysis and it has an active site to react with the synthesized uracil acetamide to afford the corresponding arylidene cellulosic MDAU(4), the latter compound which can easily due to presence of active CH=group behind a cyano group react with nitrogen nucleophile’s and cyclized with hydrazine hydrate to give pyrazole cellulosic MDPA(5). The spectral analysis of the obtained cellulosic derivatives was confirmed with FT-IR, NMR, and SEM. Additionally, a neutral red uptake analysis has been used to investigate the cytotoxic activity of the cellulosic compounds MDAC(2), MDAU(4), and MDAP(5) against the cancer cells A549 and Caco2. After 48 h, Compound MDAU(4) had a stronger inhibitory effect on the growth of A549 and Caco2, compared to control cells. Then, using QRT-PCR, the expression levels of the genes β-Catenin, c-Myc, Cyclin D1, and MMP7 in A549 cells were examined. By reducing the expression levels of the Wnt signaling cascade genes (β-Catenin, c-Myc, Cyclin D1, and MMP7) when administered to A549 cells, compound MDAU(4) was shown in this investigation to be a viable candidate compared to lung cancer. Additionally, docking simulation was used to explore the uracil cellulosic heterocycles attached to different proteins, and computational investigations of these compounds looked at how well their physical characteristics matched the outcomes of their experiments.