Human Epithelial Carcinoma Cells Research Articles

Anti-cancer drug-mediated increase in mitochondrial mass limits the application of metabolic viability-based MTT assay in cytotoxicity screening.

The high-throughput metabolic viability-based colorimetric MTT test is commonly employed to screen the cytotoxicity of different chemotherapeutic drugs. The assay assumes a cell density-dependent linear correlation with the MTT spectral absorbance. Therefore, the present study aimed to compare the cytotoxicity assessment between the MTT assay and gold standard cell number enumeration. The cytotoxicity was induced by Cisplatin, Etoposide, and Doxorubicin in human lung epithelial adenocarcinoma cells (A549) and cervix carcinoma (HeLa) cell lines. The mitochondrial mass was estimated, and immunoblotting of succinate dehydrogenase (SDH-A) was performed following drug treatment in both cell lines. Student's t-test paired analysis was employed to calculate the significance of the results, where the value p < 0.05 was considered statistically significant. The drug-induced cytotoxic response estimated by MTT absorbance did not show any significant difference with respect to control, and no correlation was observed with the enumerated cell number in both A549 and HeLa cells. Interestingly, per-cell metabolic viability was found to be increased by 1.18 to 3.26-fold (p < 0.05) following drug treatment. Further, mechanistic investigation revealed a drug concentration-dependent significant increase in mitochondrial mass (1.21 to 4.2-fold) and upregulation of SDH protein (50-70%) as well as enzymatic activity with respect to control in both A549 and Hela cells. The limitation of the MTT assay for drug-induced cytotoxicity assessment is due to increased mitochondrial mass and SDH upregulation in surviving cells, leading to enhanced formazan formation. This leads to a lack of correlation between cell number and MTT spectral absorbance, suggesting that the MTT assay may provide an erroneous conclusion for cytotoxicity assessment.

Exploring In-Silico, In-Vitro Antioxidant, and Cytotoxic Potential of Valerian wallichii by On Cervical Epithelial Carcinoma (HeLa) Cell Lines.

Traditional medicinal practices often utilize herbal remedies for treating various diseases. This study focuses on exploring the phytochemical constituents, in-silico, in-vitro antioxidant, and anticancer activities of Valerian wallichii root extracts on human cervical epithelial carcinoma (HeLa) cell lines. The molecular docking approach was employed to predict the ligand molecule's orientation within the receptor like Epidermal growth factor receptor tyrosine kinase domain (PDB ID: 1M17) using Schrodinger's GLIDE model. Among the selected phytocompounds, hesperidin exhibited promising inhibitory activity against EGFR (Epidermal Growth Factor Receptor) domain with -8.701 kcal/mol docking score and interactions with MET 769, ASP 831, ASP776, LEU694 and ASN818 residues as compared to standard doxorubicin with -7.6 kcal/mol docking score and interactions with ASP 831, ASN818 and ASP776 residues and further, various antioxidant activity was assessed and In-vitro anticancer activity against HeLa cell lines was evaluated by hydroalcoholic root extracts demonstrated antioxidant capacities, and selective cytotoxicity was observed, with IC50 : 45.759±0.42 μg/mL for the overall extract and IC50 : 30.245±0.58 μg/mL for the EAF fraction as compared to standard doxorubicin with IC50 : 25.9891±0.25 μg/mL, respectively. The present study concluded that Valerian wallichii L possesses potential human cervical epithelial carcinoma cell line inhibition properties based on the computer aided drug design models and in-vitro activity.

Anticancer Effects of Rosmarinus officinalis Leaf Extract on KB Cell Lines.

Background The value and use of medicinal plants, including the widespread cultivation of Rosmarinus officinalis, have increased rapidly. R. officinalis, a medicinal plant native to the Mediterranean, has received attention for its potential therapeutic benefits. This study evaluates R. officinalis anticancer activity using human epithelial carcinoma (KB) cell lines derived from nasopharyngeal epidermoid carcinoma. The KB cell line is known for its increased sensitivity to specific chemotherapeutic agents (CA), making it a useful model in cancer research. The impact of R. officinalis is assessed using comprehensive analyses of cell viability and gene expression. Aim This study aims to evaluate the anti-cancer effects of R. officinalis on KB cell lines. Materials and methods TheR. officinalis leaf extract was separated and used to treat KB cell lines. The cell viability of treated KB cells was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (RT-PCR) was used to analyze the expressions of matrix metalloproteinase (MMP-9) and tumor-inducing metalloproteins (TIMP-1) messenger ribonucleic acid (mRNA) genes. The statistical analysis was performed. Results This study analyzes the anticancer properties of R. officinalis on KB cell lines. The results show that increasing the concentration of rosemary extract reduces cell viability in malignant cells. Furthermore, the R. officinalis effect on the apoptotic signaling system is demonstrated by a decrease in MMP-9 and TIMP-1 mRNA expressions, as observed by RT-PCR analysis. Conclusion Patients looking for natural anticancer treatments may benefit from biogenically prepared anticancer drugs. The currentresearch focuses on R. officinalis as a potential alternative to chemically synthesized anticancer drugs.

The Fatty Acid Composition and the MTT-Cytotoxicity Test of Commercially Available Commiphora Gileadensis Balsam Oil

Commiphora gileadensis, an aromatic plant, is traditionally used in Middle Eastern countries to prevent pain and inflammation. Fatty acid composition, peroxide number and free fatty acidity analyzes of commercially available C. gileadensis balsam oil and investigation of its effect on cell viability. Commercially available C. gileadensis balsam oil fatty acid composition, peroxide number and free fatty acidity values were determined by the IUPAC IID19 method, and MTT cell viability tests were performed on L929 fibroblast and HeLa (human epithelial cervical carcinoma) cell lines. Commercially available C. gileadensis balsam oil did not exert cytotoxic effects on both L929 fibroblast and HeLa (human epithelial cervical carcinoma) cell lines and promoted the growth of cell lines. Due to its growth promoting feature on L929 fibroblast cells, which is a healthy cell line, this material can be used as a cell culture medium additive.

Identification by methods of steady-state and kinetic spectrofluorimetry of endogenous porphyrins and flavins sensitizing the formation of reactive oxygen species in cancer cells.

The question about acceptor molecules of optical radiation that determine the effects of photobiomodulation in relation to various types of cells still remains the focus of attention of researchers. This issue is most relevant for cancer cells, since, depending on the parameters of optical radiation, light can either stimulate their growth or inhibit them and lead to death. This study shows that endogenous porphyrins, which have sensitizing properties, may play an important role in the implementation of the effects of photobiomodulation, along with flavins. For the first time, using steady-state and kinetic spectrofluorimetry, free-base porphyrins and their zinc complexes were discovered and identified in living human cervical epithelial carcinoma (HeLa) cells, as well as in their extracts. It has been shown that reliable detection of porphyrin fluorescence in cells is hampered by the intense fluorescence of flavins due to their high concentration (micromolar range) and higher (compared to tetrapyrroles) fluorescence quantum yield. Optimization of the spectral range of excitation and the use of extractants that provide multiple quenching of the flavin component while increasing the emission efficiency of tetrapyrroles makes it possible to weaken the contribution of the flavin component to the recorded fluorescence spectra.

Phytochemical composition, biological activity and anti-inflammatory potential of acetone extract from the lichen Platismatia glauca (L.) W.L. Culb. & C.F. Culb

This investigation examined the antioxidant, antimicrobial, cytotoxic, and anti-inflammatory activities of the acetone extract of the lichen Platismatia glauca (L.) W.L. Culb. & C.F. Culb. (PGAE). The phytochemical study of PGAE showed presence of seven compounds: salazinic acid, β-orcinol carboxylic acid, 3-hydroxyphysodalic acid, physodalic acid, physodic acid, atranorin, and chloroatranorin. The antimicrobial potential was determined by microdilution which showed that S. aureus was most sensitive to the effect of PGAE with MIC value 0.312 mg/ml. Antioxidant activity was evaluated by using DPPH method. The obtained IC50 value for PGAE was 194.30 ± 3.32 µg/ml. The cytotoxic effect of the extract was evaluated by MTT test and the strongest activity was towards human epithelial carcinoma cells with IC50 value of 59.10 ± 0.46 µg/ml. The findings revealed that the application of lichen extracts decreased the paw edoema in a dose-dependent manner at 1, 2, 3, and 4 h following carrageenan administration.

Effect of COVID-19 mRNA Vaccine on Human Lung Carcinoma Cells In Vitro by Means of Raman Spectroscopy and Imaging.

The effect of COVID-19 mRNA vaccine on human lung epithelial carcinoma cells (A549) in vitro as a convenient preclinical model was studied by means of Raman spectroscopy and imaging. The article focuses on Raman imaging as a tool to explore apoptosis and oxidative phosphorylation in mitochondrial dysfunctions. The Raman results demonstrate alterations in the oxidation-reduction pathways associated with cytochrome c. We found that the COVID-19 mRNA vaccine downregulates the concentration of cytochrome c upon incubation with tumorous lung cells. The concentration of the oxidized form of cytochrome c in the mitochondria of lung cells decreases upon incubation with the COVID-19 mRNA vaccine. A lower concentration of oxidized cytochrome c in mitochondria illustrates lower effectiveness of oxidative phosphorylation (respiration), reduced apoptosis, and lessened ATP production. Moreover, mRNA vaccine significantly increases de novo lipids synthesis in lipid droplets up to 96 h and alterations in biochemical composition. It seems that the lipid composition of cells returns to the normal level for a longer incubation time (14 days). In the cell nucleus, the mRNA vaccine does not produce statistically significant changes.

Rhamnetin, a nutraceutical flavonoid arrests cell cycle progression of human ovarian cancer (SKOV3) cells by inhibiting the histone deacetylase 2 protein

Overexpression of HDAC 2 promotes cell proliferation in ovarian cancer. HDAC 2 is involved in chromatin remodeling, transcriptional repression, and the formation of condensed chromatin structures. Targeting HDAC 2 presents a promising therapeutic approach for correcting cancer-associated epigenetic abnormalities. Consequently, HDAC 2 inhibitors have evolved as an attractive class of anti-cancer agents. This work intended to investigate the anti-cancer abilities and underlying molecular mechanisms of Rhamnetin in human epithelial ovarian carcinoma cells (SKOV3), which remain largely unexplored. We employed various in vitro methods, including MTT, apoptosis study, cell cycle analysis, fluorescence microscopy imaging, and in vitro enzymatic HDAC 2 protein inhibition, to examine the chemotherapeutic sensitivity of Rhamnetin in SKOV3 cells. Additionally, we conducted in silico studies using molecular docking, MD simulation, MM-GBSA, DFT, and pharmacokinetic analysis to investigate the binding interaction mechanism within Rhamnetin and HDAC 2, alongside the compound’s prospective as a lead candidate. The in vitro assay confirmed the cytotoxic effects of Rhamnetin on SKOV3 cells, through its inhibition of HDAC 2 activity. Rhamnetin, a nutraceutical flavonoid, halted at the G1 phase of the cell cycle and triggered apoptosis in SKOV3 cells. Furthermore, computational studies provided additional evidence of its stable binding to the HDAC 2 protein’s binding site cavity. Based on our findings, we conclude that Rhamnetin effectively promotes apoptosis and mitigates the proliferation of SKOV3 cells through HDAC 2 inhibition. These results highlight Rhamnetin as a potential lead compound, opening a new therapeutic strategy for human epithelial ovarian cancer. Communicated by Ramaswamy H. Sarma

Steric hindrance and charge influence on the cytotoxic activity and protein binding properties of diruthenium complexes

Paddlewheel diruthenium complexes are being used as metal-based drugs. It has been proposed that their charge and steric properties determine their selectivity towards proteins. Here, we explore these parameters using the first water-soluble diruthenium complex bearing two formamidinate ligands, [Ru2Cl(DPhF)2(O2CCH3)2], and two derivatives, [Ru2Cl(DPhF)(O2CCH3)3] and K2[Ru2(DPhF)(CO3)3] (DPhF− = N,N′-diphenylformamidinate), with one formamidinate. Their protein binding properties have been assessed employing hen egg white lysozyme (HEWL). The results confirm the relationship between the type of interaction (coordinate/non-coordinate bonds) and the charge of diruthenium complexes. The crystallization medium is also a key factor. In all cases, diruthenium species maintain the M–M bond and produce stable adducts. The antiproliferative properties of these diruthenium complexes have been evaluated on an eukaryotic cell-based model. Our data show a correlation between the number of the formamidinate ligands and the anticancer activity of the diruthenium derivatives against human epithelial carcinoma cells. Increased cytotoxicity may be related to increased steric hindrance and Ru25+ core electronic density. However, the effect of increasing the lipophilicity of diruthenium species by introducing a second N,N′-diphenylformamidinate must be also considered. This work illustrates a systematic approach to shed light on the relevant properties of diruthenium compounds to design metal-based metallodrugs and diruthenium metalloenzymes.

Characterization and Bioactivity of Piper chaudocanum L. Extract-Doped ZnO Nanoparticles Biosynthesized by Co-Precipitation Method.

Green synthesis and nanomaterials have been the current trends in biomedical materials. In this study, Piper chaudocanum L. leaf extract-doped ZnO nanoparticles (PLE-doped ZnO NPs), a novel nanomaterial, were studied including the synthesis process, and the biomedical activity was evaluated. PLE-doped ZnO NPs were synthesized by the co-precipitation method, with differences in the synthesis procedures and dosages of the extract. The X-ray diffraction, Fourier transform infrared, scanning electron microscopy, energy dispersive X-ray spectroscopy, Brunauer-Emmett-Teller, ultraviolet-visible diffuse reflectance spectroscopy, and photoluminescence spectrum analysis results showed that the biosynthesized PLE-doped ZnO NPs were pure and in a hexagonal wurtzite phase. The PLE-doped NPs were synthesized by adding the extract to the zinc acetate solution before adjusting the pH and exhibited the smallest size (ZPS50 was 22 nm), the richest in the surface organic functional groups and the best optical activity. The highest antibacterial activity against P. aeruginosa and S. aureus was observed at 100 µg/mL of ZPS50 NPs, and the inhibition zone reached 42 and 39 nm, respectively. Moreover, ZPS50 NPs showed a moderate effectiveness against KB cancer cells with an IC50 value of 43.53 ± 2.98 µg/mL. This present study's results suggested that ZPS50 NPs could be a promising nanomaterial in developing drugs for treating human epithelial carcinoma cells and infectious illnesses.

Reduction of oral pathogens and oxidative damage in the CAL 27 cell line by Rosmarinus officinalis L. and Taraxacum officinale Web. extracts

Ethnopharmacological relevanceDandelion (Taraxacum officinale Web.) and rosemary (Rosmarinus officinalis L.) are treasured botanicals with a long usage history in traditional herbal practices worldwide. Dandelion was used to treat kidney, spleen, and liver disease, as well as cardiovascular disease, diabetes, and bacterial infections, whereas rosemary was used to treat pain, spasms, and to improve blood circulation. Aim of the studyThe aim of this study was to determine the influence of rosemary and dandelion leaves aqueous extracts on the human tongue epithelial carcinoma cell line (CAL 27) at the level of interaction between oral microbiota and tongue epithelial cells, genomic damage, and H2O2 - induced oxidative damage protection. Materials and methodsThe polyphenolic composition of the extracts was determined by spectrophotometric and HPLC analyses. After extract treatment, cytotoxic impact and ROS generation in CAL 27 cells were measured using the MTT assay and the 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay, respectively. Microdilutions were applied to investigate the antimicrobial and adhesive properties against representatives of the oral microbiota. The single-cell gel electrophoresis (comet assay) and cytokinesis-blocked micronucleus cytome assay (CBMN cyt) were used to detect induced genomic damages. ResultsBoth extracts increased the adhesion of the lactic acid bacteria L. plantarum but decreased the adhesion of the bacterial pathogens S. enterica serovar Typhimurium LT21 and E. coli K-12 MG1655 adhesion onto CAL 27 cells. 1 h treatment with 5x concentrated dandelion extract and 1x, 2.5x, and 5x of rosemary extract caused an increase in comet tail intensity. CBMN cyt results demonstrated a significant increase in micronucleus formation even at concentrations several times lower than the usual bioactive compound concentrations found in a cup of beverage, with higher concentrations also inducing cell apoptosis and necrosis. Rosemary extract showed a protective effect against H2O2 - induced oxidative damage by decreasing the apoptotic cell number, probably preventing mutations leading to tumor aggressiveness, invasion, and metastasis. ConclusionsBoth tested extracts demonstrated their usefulness in maintaining good oral bacteria balance and their protective capability as powerful antitumor agents by causing a protective apoptotic effect in tumor cell line already at the dosage of an average daily cup.

Chitosan membrane drafting silver-immobilized graphene oxide nanocomposite for banana preservation: Fabrication, physicochemical properties, bioactivities, and application

In this study, silver-immobilized graphene oxide/chitosan (AGC/CTS) membranes were assembled by the solvent evaporation method, wherein Curcuma longa extract was used to synthesize silver-immobilized graphene oxide (AGC) nanocomposite. The characterization results showed that the AGC was successfully synthesized with AgNPs distributed quite evenly on GO sheets. The as-prepared AGC also exhibited high antibacterial activity and low cytotoxicity towards normal cell lines compared to human epithelial carcinoma cell lines. Besides, the fabrication of AGC/CTS membranes was additionally assessed with different AGC ratios and thicknesses. The results revealed the membrane containing 3 wt% of AGC with great hygroscopicity and elastic modulus of 27.03 ± 3.07 MPa. The samples also performed excellent bactericidal capability, along with good mechanical properties for banana preservation. Therewithal, the membrane-coated bananas were also elucidated to ripen at slower paces and less damage, with no appearance of patches of mold on the banana peel surface, eventually prolonging the shelf life of bananas up to 10 days as compared to the non-coated ones. The aforesaid results confirm the potential application of the AGC/CTS membrane as a safe and alternative fruit preservation agent in the food industry.

COMPOSITION ANALYSIS OF E-LIQUIDS AND THEIR EFFECTS ON HEALTHY LIVER AND PHARYNGEAL CARCINOMA CELL LINES

Electronic cigarettes have become popular worldwide in recent years although their effects on human health are still not properly known. The lack of regulations brings a problem of inconsistency between ingredients and the product label. We aimed to analyse the contents of widely used e-liquids and their effects on two different cell lines. Eleven e-liquid samples were selected according to their availability and popularity. Nicotine, propylene glycol (PG), glycerine (GLY), and volatile compounds in e-liquids were analysed by High-Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC). 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay was used to determine the effects of e-liquids on transformed human normal liver epithelial cell line (THLE-2) and human pharyngeal carcinoma cell line (Detroit 562). Nicotine amounts were found to be consistent with product labels. and GLY were not only different between brands but also for products within the same brand. THLE-2 cell viability was inversely correlated with e-liquid concentration. However, decreases in cell viability were not correlated with nicotine amount. Interestingly, effects of several samples on Detroit 562 cells were triphasic; decrease in viability at lower doses, cell survival in mid-concentrations and loss of viability in highest doses. The analytical composition of e-liquids differs greatly among products which corresponds to different cellular effects. Viability of cancer cells does not change in a dose-dependent manner, which suggest that cellular differences may play role in the outcome of these products.

Effects of Drying Temperature and Solvents on In Vitro Diabetic Wound Healing Potential of Moringa oleifera Leaf Extracts.

The delayed healing of wounds among people with diabetes is a severe problem worldwide. Hyperglycemia and increased levels of free radicals are the major inhibiting factors of wound healing in diabetic patients. Plant extracts are a rich source of polyphenols, allowing them to be an effective agent for wound healing. Drying temperature and extraction solvent highly affect the stability of polyphenols in plant materials. However, there is a need to optimize the extraction protocol to ensure the efficacy of the final product. For this purpose, the effects of drying temperature and solvents on the polyphenolic composition and diabetic wound healing activity of Moringa oleifera leaves were examined in the present research. Fresh leaves were oven dried at different temperatures (10 °C, 30 °C, 50 °C, and 100 °C) and extracted in three solvents (acetone, ethanol, and methanol) to obtain twelve extracts in total. The extracts were assessed for free radical scavenging and antihyperglycemic effects using DPPH (2,2-diphenylpicrylhydrazyl) and α- glucosidase inhibition assays. Alongside this, a scratch assay was performed to evaluate the cell migration activity of M. oleifera on the human retinal pigment epithelial cell line. The cytotoxicity of the plant extracts was assessed on human retinal pigment epithelial (RPE) and hepatocellular carcinoma (Huh-7) cell lines. Using high-performance liquid chromatography, phenolic compounds in extracts of M. oleifera were identified. We found that an ethanol-based extract prepared by drying the leaves at 10 °C contained the highest amounts of identified polyphenols. Moringa oleifera extracts showed remarkable antioxidant, antidiabetic, and cell migration properties. The best results were obtained with leaves dried at 10 °C and 30 °C. Decreased activities were observed with drying temperatures of 50 °C and above. Moreover, M. oleifera extracts exhibited no toxicity on RPE cells, and the same extracts were cytotoxic for Huh-7 cells. This study revealed that M. oleifera leaves extracts can enhance wound healing in diabetic conditions due to their antihyperglycemic, antioxidant, and cell migration effects. The leaves of this plant can be an excellent therapeutic option when extracted at optimum conditions.

Novel Non-Viral Vectors Based on Pluronic® F68PEI with Application in Oncology Field.

Copolymers composed of low-molecular-weight polyethylenimine (PEI) and amphiphilic Pluronics® are safe and efficient non-viral vectors for pDNA transfection. A variety of Pluronic® properties provides a base for tailoring transfection efficacy in combination with the unique biological activity of this polymer group. In this study, we describe the preparation of new copolymers based on hydrophilic Pluronic® F68 and PEI (F68PEI). F68PEI polyplexes obtained by doping with free F68 (1:2 and 1:5 w/w) allowed for fine-tuning of physicochemical properties and transfection activity, demonstrating improved in vitro transfection of the human bone osteosarcoma epithelial (U2OS) and oral squamous cell carcinoma (SCC-9) cells when compared to the parent formulation, F68PEI. Although all tested systems condensed pDNA at varying polymer/DNA charge ratios (N/P, 5/1−100/1), the addition of free F68 (1:5 w/w) resulted in the formation of smaller polyplexes (<200 nm). Analysis of polyplex properties by transmission electron microscopy and dynamic light scattering revealed varied polyplex morphology. Transfection potential was also found to be cell-dependent and significantly higher in SCC-9 cells compared to the control bPEI25k cells, as especially evident at higher N/P ratios (>25). The observed selectivity towards transfection of SSC-9 cells might represent a base for further optimization of a cell-specific transfection vehicle.

Cytotoxic Properties of C17 Polyacetylenes from the Fresh Roots of Panax ginseng on Human Epithelial Ovarian Cancer Cells.

Although C17 polyacetylenes from Panax ginseng exhibit cytotoxic properties against various tumor cells, there have been few experiments on epithelial ovarian carcinoma cells. This study aimed to investigate the cytotoxic effects of C17 polyacetylenes from P. ginseng against ovarian cancer cell lines. Four unreported (1–4) and fifteen known (5–19) C17 polyacetylenes were obtained from the roots of P. ginseng using repeated chromatography (open column, MPLC, and preparative HPLC). The chemical structures of all the compounds were determined by analyzing their spectroscopic data (NMR, IR, and optical rotation) and HR-MS. The structures of new polyacetylenes were elucidated as (3S,8S,9R,10R)-(-)-heptadeca-9,10-epoxy-4,6-diyne-3,8-diyl diacetate (1), (3S,8S,9R,10R)-(−)-heptadeca-1-en-9,10-epoxy-4,6-diyne-3,8-diyl diacetate (2), (−)-haptadeca-9,10-epoxy-8-methoxy-4,6-diyne-3,11-diol (3), and (3R,9R,10R)-(+)-3-acetoxy-9,10-dihydroxyheptadeca-1-en-4,6-diyne (4), named ginsenoynes O, P, and Q, and 3-acetyl panaxytriol, respectively. Subsequently, in vitro experiments on A2780 and SKOV3 human epithelial ovarian carcinoma cells were performed to assess the cytotoxic properties of the isolates. Among the isolates, panaquinquecol 4 (15) exhibited the most remarkable cytotoxic effects on both human ovarian cancer cells A2780 (IC50 value of 7.60 μM) and SKOV3 (IC50 value of 27.53 μM). Therefore, C17 polyacetylenes derived from P. ginseng may warrant further investigation for their therapeutic potential in epithelial ovarian cancer.

A novel tumor-targeting strain of Xenorhabdus stockiae exhibits potent biological activities.

Xenorhabdus are symbionts of soil entomopathogenic nematodes of the genus Steinernema presenting two distinct forms in their life cycle, and can produce a broad range of bioactive compounds. In this study, a novel Xenorhabdus stockiae strain HN_xs01 was isolated from a soil sample via an entrapment method using Galleria melonella nematodes. The supernatants of strain HN_xs01 exhibited antimicrobial properties against Gram-negative and Gram-positive bacteria, and insecticidal properties against Helicoverpa armigera larvae, and antitumor properties as well. Moreover, three linear rhabdopeptides (1, 2 and 3) were identified from strain HN_xs01 using nuclear magnetic resonance analysis, which exhibited significant cytotoxic activity against the human epithelial carcinoma cell line A431 and the human chronic myelogenous leukemia cell line K562. Some bacteria have been reported to colonize the tumor region, and we determined that HN_xs01 could grow in tumor xenografts in this study. HN_xs01 invaded and replicated in B16 melanoma cells grafted into C57BL/6 mice, resulting in tumor inhibition. Moreover, strain HN_xs01 not only merely aggregated in the tumor environment, but also prevented pulmonary metastasis. It caused fragmentation of vessels and cell apoptosis, which contributed to its antitumor effect. In conclusion, X. stockiae HN_xs01 is a novel tumor-targeting strain with potential applications in medicinal and agricultural fields.

Microwave Reduced Graphene Oxide as Efficient NIR Photothermal Agent

Current study reports the enhanced cancer cells photothermal ablation efficiency of Microwave Reduced Graphene Oxide (MRGO). Reduction of chemically exfoliated graphene oxide has been carried out using a microwave (700W for 5 minutes). The produced MRGO have been characterized with TEM, SEM, XRD, FTIR, RAMAN, AFM and UV-Vis spectroscopy. MRGO nano size sheets with average lateral dimension ~200nm, exhibited higher NIR absorption efficiency, in comparison to Graphene Oxide (GO). Photothermal efficacy (at optimized NIR laser 808 nm, power of 5.0W/cm2 for 5 min) of MRGO have been tested against human alveolar epithelial carcinoma cell (A549) and human colorectal carcinoma cells (HCT116). As a result, a significant decrease in cell viability by 84% and 80% for A549 and HCT116 cell lines respectively has been estimated. No significant toxicity has been observed with MRGO (in absence of NIR treatment) at the concentrations well above the doses needed for photothermal heating against the same cancer cells. Our study introduces MRGO as a biocompatible and efficient photothermal agent.

Combined experimental and theoretical analyses on design, synthesis, characterization, and in vitro cytotoxic activity evaluation of some novel imino derivatives containing pyrazolone ring

In this research, some novel Schiff base derivatives 10–18 were synthesized for the first time, characterized, and tested for their anticancer activities. Spectroscopic characterization of the synthesized molecules 1–18 was carried out by using elemental analysis (C, H, N, S), FT-IR, HRMS, 1H- and 13C- NMR and DEPT-135 spectroscopic techniques. The antiproliferative activity studies of all newly synthesized compounds were tested against different human cancer cell lines, including colon and liver, using an MTT assay for 48 h. Under specified experimental conditions, three molecules (13-15) demonstrated higher cytotoxic activity than other molecules (1-12, 16-18) toward human epithelial colon colorectal cancer cell line (DLD-1) with IC50 values of 67.88, 56.53, and 48.70 μM, respectively. Besides, two different molecules (8 and 17) were found to have more toxic effects than molecules (1-7, 9-16, 18) against human liver epithelial hepatocellular carcinoma cell line (HepG2) with IC50 values of 65.72 and 54.84 μM, respectively. The selectivity of these compounds, which show high activity, was also tested on a healthy human cell line (Wl-38). Compounds (1–18) were docked against target proteins (PDB ID: 5ETY and 6V9C) representing DLD-1 and HepG2 cell lines.

Critical roles for EGFR and EGFR-HER2 clusters in EGF binding of SW620 human carcinoma cells.

Epidermal growth factor (EGF) signalling regulates normal epithelial and other cell growth, with EGF receptor (EGFR) overexpression reported in many cancers. However, the role of EGFR clusters in cancer and their dependence on EGF binding is unclear. We present novel single-molecule total internal reflection fluorescence microscopy of (i) EGF and EGFR in living cancer cells, (ii) the action of anti-cancer drugs that separately target EGFR and human EGFR2 (HER2) on these cells and (iii) EGFR–HER2 interactions. We selected human epithelial SW620 carcinoma cells for their low level of native EGFR expression, for stable transfection with fluorescent protein labelled EGFR, and imaged these using single-molecule localization microscopy to quantify receptor architectures and dynamics upon EGF binding. Prior to EGF binding, we observe pre-formed EGFR clusters. Unexpectedly, clusters likely contain both EGFR and HER2, consistent with co-diffusion of EGFR and HER2 observed in a different model CHO-K1 cell line, whose stoichiometry increases following EGF binding. We observe a mean EGFR : EGF stoichiometry of approximately 4 : 1 for plasma membrane-colocalized EGFR–EGF that we can explain using novel time-dependent kinetics modelling, indicating preferential ligand binding to monomers. Our results may inform future cancer drug developments.