HeLa Research Articles

Preparation and Evaluation of a Novel 99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent.

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [99mTc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro. In HeLa cell experiments, the uptake of [99mTc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumor-bearing mice, [99mTc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [99mTc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [99mTc]Tc-CNPN is a promising tumor imaging agent that targets PARP.

Chondroitin sulfate-functionalized selenium nanoparticle-induced S-phase cell cycle arrest and apoptosis in HeLa Cells.

This study aimed to evaluate the anti-cervical cancer activity of chondroitin sulfate-functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose- and time-dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S-phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down-regulated expression levels of cyclin A and CDK2 and up-regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl-2, resulting in the release of cytochrome C from mitochondria and activating caspase-3/8/9 for caspase-dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS-induced S-phase arrest and cell apoptosis. These data show that SeCS has anti-tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. PRACTICAL APPLICATION: In our previous study, we used chondroitin sulfate to stabilize nano-selenium to obtain SeCS to improve the bioactivity and stability of nano-selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients.

Biotinylated Theranostic Amphiphilic Polyurethane for Targeted Drug Delivery.

In the area of drug delivery aided by stimuli-responsive polymers, the biodegradability of nanocarriers is one of the major challenges that needs to be addressed with the utmost sincerity. Herein, a hydrogen sulfide (H2S) responsive hydrophobic dansyl-based trigger molecule is custom designed and successfully incorporated into the water-soluble polyurethane backbone, which is made of esterase enzyme susceptible urethane bonds. The amphiphilic polyurethanes, PUx (x = 2 and 3) with a biotin chain end, formed self-assembled nanoaggregates. A hemolysis and cytotoxicity profile of doxorubicin (DOX)-loaded biotinylated PU3 nanocarriers revealed that it is nonhemolytic and has excellent selectivity toward HeLa cells (biotin receptor-positive cell lines) causing ∼60% cell death while maintaining almost 100% cell viability for HEK 293T cells (biotin receptor-negative cell lines). Furthermore, better cellular internalization of DOX-loaded fluorescent nanocarriers in HeLa cells than in HEK 293T cells confirmed receptor-mediated endocytosis. Thus, this work ensures that the synthesized polymers serve as biodegradable nanocarriers for anticancer therapeutics.

Integrated Platform for Large-Scale Quantitative Profiling of Phosphotyrosine Signaling Complexes Based on Cofractionation/Mass Spectrometry and Complex-Centric Algorithm.

The scarcity and dynamic nature of phosphotyrosine (pTyr)-modified proteins pose a challenge for researching protein complexes with pTyr modification, which are assembled through multiple protein-protein interactions. We developed an integrated complex-centric platform for large-scale quantitative profiling of pTyr signaling complexes based on cofractionation/mass spectrometry (CoFrac-MS) and a complex-centric algorithm. We initially constructed a trifunctional probe based on pTyr superbinder (SH2-S) for specifically binding and isolation of intact pTyr protein complexes. Then, the CoFrac-MS strategy was employed for the identification of pTyr protein complexes by integrating ion exchange chromatography in conjunction with data independent acquisition mass spectrometry. Furthermore, we developed a novel complex-centric algorithm for quantifying protein complexes based on the protein complex elution curve. Utilizing this algorithm, we effectively quantified 216 putative protein complexes. We further screened 21 regulated pTyr protein complexes related to the epidermal growth factor signal. Our study engenders a comprehensive framework for the intricate examination of pTyr protein complexes and presents, for the foremost occasion, a quantitative landscape delineating the composition of pTyr protein complexes in HeLa cells.

LncRNA CDKN2B-AS1 regulates collagen expression.

The long noncoding RNA CDKN2B-AS1 harbors a major coronary artery disease risk haplotype, which is also associated with progressive forms of the oral inflammatory disease periodontitis as well as myocardial infarction (MI). Despite extensive research, there is currently no broad consensus on the function of CDKN2B-AS1 that would explain a common molecular role of this lncRNA in these diseases. Our aim was to investigate the role of CDKN2B-AS1 in gingival cells to better understand the molecular mechanisms underlying the increased risk of progressive periodontitis. We downregulated CDKN2B-AS1 transcript levels in primary gingival fibroblasts with LNA GapmeRs. Following RNA-sequencing, we performed differential expression, gene set enrichment analyses and Western Blotting. Putative causal alleles were searched by analyzing associated DNA sequence variants for changes of predicted transcription factor binding sites. We functionally characterized putative functional alleles using luciferase-reporter and antibody electrophoretic mobility shift assays in gingival fibroblasts and HeLa cells. Of all gene sets analysed, collagen biosynthesis was most significantly upregulated (Padj=9.7 × 10- 5 (AUC > 0.65) with the CAD and MI risk gene COL4A1 showing strongest upregulation of the enriched gene sets (Fold change = 12.13, Padj = 4.9 × 10- 25). The inflammatory "TNFA signaling via NFKB" gene set was downregulated the most (Padj=1 × 10- 5 (AUC = 0.60). On the single gene level, CAPNS2, involved in extracellular matrix organization, was the top upregulated protein coding gene (Fold change = 48.5, P < 9 × 10- 24). The risk variant rs10757278 altered a binding site of the pathogen responsive transcription factor STAT1 (P = 5.8 × 10- 6). rs10757278-G allele reduced STAT1 binding 14.4% and rs10757278-A decreased luciferase activity in gingival fibroblasts 41.2% (P = 0.0056), corresponding with GTEx data. CDKN2B-AS1 represses collagen gene expression in gingival fibroblasts. Dysregulated collagen biosynthesis through allele-specific CDKN2B-AS1 expression in response to inflammatory factors may affect collagen synthesis, and in consequence tissue barrier and atherosclerotic plaque stability.

Sol–Gel Synthesis and Characterizations of Spinel Nickel Chromite (NiCr2O4) Nanoparticles to Study their Photocatalytic, Antibacterial and Anticancer Activities

A facile and cost-effective sol–gel technique has been used to synthesize nickel chromite (NiCr2O4) nanoparticles (NCNPs) at 700°C to investigate their photocatalytic together with antibacterial and anticancer activities. The synthesized nanopowder was characterized by Thermogravimetric thermal analysis (TG-DTA), X-ray Diffraction Spectroscopy (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), High-Resolution Transmission Electron Microscopy (HR-TEM), Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Photon Electroscopy (XPS) and UV–Visible Diffuse Reflectance Spectroscopy (UV-DRS) and Photoluminescence (PL). Beyond 700°C, the thermal durability of NCNPs was confirmed by TG-DTA analysis. The synthesized NPs were cubic structured corresponding to their spinel structure, a crystallite size of 38[Formula: see text]nm and an optical bandgap of 2.7[Formula: see text]eV. The PL spectra revealed emission bands in the visible and UV regions. The surface-phase-pure elemental and electronic arrangement of the NCNPs were verified by X-ray photon spectroscopy. Photocatalytic activity of NCNPs against Methylene Blue dye revealed 89% degradation in 1[Formula: see text]h. The in vitro antibacterial and anticancer activities of NCNPs were also examined. Among the tested microbes, Staphylococcus aureus exhibited the highest level of sensitivity (9[Formula: see text]mm), while Escherichia coli had the lowest (5[Formula: see text]mm) against NCNPs. The MTT test revealed the significant cytotoxicity of NCNPs against carcinogenic HeLa and MCF-7 cells. Thus, the synthesized NCNPs could be rated as potential photocatalytic, bactericidal and anticarcinogenic agents.

Picoliter Single-Cell Reactor for Proteome Profiling by In Situ Cell Lysis, Protein Immobilization, Digestion, and Droplet Transfer.

Global profiling of single-cell proteomes can reveal cellular heterogeneity, thus benefiting precision medicine. However, current mass spectrometry (MS)-based single-cell proteomic sample processing still faces technical challenges associated with processing efficiency and protein recovery. Herein, we present an innovative sample processing platform based on a picoliter single-cell reactor (picoSCR) for single-cell proteome profiling, which involves in situ protein immobilization and sample transfer. PicoSCR helped minimize surface adsorptive losses by downscaling the processing volume to 400 pL with a contact area of less than 0.4 mm2. Besides, picoSCR reached highly efficient cell lysis and digestion within 30 min, benefiting from optimal reagent and high reactant concentrations. Using the picoSCR-nanoLC-MS system, over 1400 proteins were identified from an individual HeLa cell using data-dependent acquisition mode. Proteins with copy number below 1000 were identified, demonstrating this system with a detection limit of 1.7 zmol. Furthermore, we profiled the proteome of circulating tumor cells (CTCs). Data are available via ProteomeXchange with the identifier PXD051468. Proteins associated with epithelial-mesenchymal transition and neutrophil extracellular traps formation (which are both related to tumor metastasis) were observed in all CTCs. The cellular heterogeneity was revealed by differences in signaling pathways within individual cells. These results highlighted the potential of the picoSCR platform to help discover new biomarkers and explore differences in biological processes between cells.

Retraction Note: Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

Retraction Note: Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

Ethanolic extract from Sophora moorcroftiana inhibit cell proliferation and alter the mechanical properties of human cervical cancer

BackgroundCervical cancer is one of the most common gynecological malignancies. Previous studies have shown that the ethanol extract of Sophora moorcroftiana seeds (EESMS) possesses an antiproliferative effect on several tumors in vitro. Therefore, in this study, we assessed the impact of EESMS on human cervical carcinoma (HeLa) cell proliferation.MethodsThe proliferation and apoptotic effects of HeLa cells treated with EESMS were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, dual acridine orange/ethidium bromide double staining, flow cytometry, and western blotting. Single-cell level atomic force microscopy (AFM) was conducted to detect the mechanical properties of HeLa cells, and proteomics and bioinformatics methods were used to elucidate the molecular mechanisms of EESMS.ResultsEESMS treatment inhibited HeLa cell proliferation by blocking the G0/G1 phase, increasing the expression of Caspase-3 and affecting its mechanical properties, and the EESMS indicated no significant inhibitory effect on mouse fibroblasts L929 cell line. In total, 218 differentially expressed proteins were identified using two-dimensional electrophoresis, and eight differentially expressed proteins were successfully identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The differentially expressed proteins were involved in various cellular and biological processes.ConclusionThis study provides a perspective on how cells change through biomechanics and a further theoretical foundation for the future application of Sophora moorcroftiana as a novel low-toxicity chemotherapy medication for treating human cervical cancer.

Identification of novel compound heterozygous ZFP36L2 variants implicated in oocyte maturation defects and female infertility.

To explore the pathogenesis of oocyte maturation defects. Whole exome sequencing was conducted to identify potential variants, which were then confirmed within the pedigree through Sanger sequencing. The functional characterization of the identified variants responsible for the disease, including their subcellular localization, protein levels, and interactions with other proteins, was verified through transient transfection in HeLa cells in vitro. Additionally, we employed real-time RT-PCR and single-cell RNA sequencing to examine the impact of ZFP36L2 pathogenic variants on mRNA metabolism in both HeLa cells and mouse or human oocytes. A novel compound heterozygous variant in ZFP36L2 (c.186T > G, p.His62Gln and c.869C > T, p.Pro290Leu) was discovered in a patient with oocyte maturation defects. Our findings indicate that these variants lead to compromised binding capacity of the ZFP36L2-CONT6L complex and impaired mRNA degradation in HeLa cells and mouse oocytes. Furthermore, we characterized the changes in the human oocyte transcriptome associated with ZFP36L2 variants, with a particular emphasis on cell division, mitochondrial function, and ribosome metabolism. This study broadens the mutation spectrum of ZFP36L2 and constitutes the first report of human oocyte transcriptome alterations linked to ZFP36L2 variants. In conjunction with existing knowledge of ZFP36L2, our research lays the groundwork for genetic counseling aimed at addressing female infertility.

Bioinspired Hg2+-sensing fluorogenic probe based on amino acid–functionalized rhodamine

Inspired by the suitability of rhodamine spirolactam switching for superresolution imaging and fluorescent probe development, we herein synthesized rhodamine-based probes with sulfur-bearing amine and amino acid moieties and screened their abilities to respond to Hg2+ in the presence of other metal ions. The probe based on S-methylcysteine methyl ester–substituted rhodamine 6G (Rho6G-6) was identified as optimal because of its straightforward synthesis and rapid, selective, and sensitive (detection limit = 8 × 10–9 M) response to Hg2+ manifested by absorption spectrum and emission color changes. The complexation of Hg2+ by Rho6G-6 was examined by absorbance and fluorescence analyses, electrospray ionization–mass spectrometry, and 1H nuclear magnetic resonance (NMR) titration experiments. Furthermore, the practical applicability of the above probe was demonstrated by naked-eye colorimetric Hg2+ detection using paper test strips and the fluorescence-based qualitative mapping of the Hg2+ distribution in living HeLa cells and the organs of live mice. Thus, unlike other probe design strategies, the use of flexible S-methyl amino acids for Hg2+ binding provides new opportunities and strategies for photopromoting the ring switching of the rhodamine spirothiolactam.

Bloom syndrome DNA helicase mitigates mismatch repair-dependent apoptosis

Generation of O6-methylguanine (O6-meG) by DNA-alkylating agents such as N-methyl N-nitrosourea (MNU) activates the multiprotein mismatch repair (MMR) complex and the checkpoint response involving ATR/CHK1 and ATM/CHK2 kinases, which may in turn trigger cell cycle arrest and apoptosis. The Bloom syndrome DNA helicase BLM interacts with the MMR complex, suggesting functional relevance to repair and checkpoint responses. We observed a strong interaction of BLM with MMR proteins in HeLa cells upon treatment with MNU as evidenced by co-immunoprecipitation as well as colocalization in the nucleus as revealed by dual immunofluorescence staining. Knockout of BLM sensitized HeLa MR cells to MNU-induced cell cycle disruption and enhanced expression of the apoptosis markers cleaved caspase-9 and PARP1. MNU-treated BLM-deficient cells also exhibited a greater number of 53BP1 foci and greater phosphorylation levels of H2AX at S139 and RPA32 at S8, indicating the accumulation of DNA double-strand breaks. These findings suggest that BLM prevents double-strand DNA breaks during the MMR-dependent DNA damage response and mitigates O6-meG-induced apoptosis.

Hydrophilically-modified poly(ε-caprolactone) with zwitterionic sulfobetaine/tertiary amine and their self-assemblies in water

To achieve hydrophilic modification of poly(ε-caprolactone) (PCL), a series of amphiphilic copolymers, poly(ε-caprolactone)-b-poly(N,N-dimethylaminoethyl methacrylate-co-sulfobetaine methacrylate) (PCDSs), were synthesized with varying sulfobetaine compositions using a three-step synthetic strategy. Firstly, the hydroxyl-terminated polymer, PDMAEMA-OH was synthesized through free radical polymerization using AIBN as an initiator and 2-mercaptoethanol as a chain transfer agent. Subsequently, the block copolymer poly(ε-caprolactone)-b- poly(N,N-dimethylamino ethylmethacrylate) (PCD) was prepared through ring-opening polymerization of PDMAEMA-OH and ε-caprolactone employing Sn(OCt)2 as the catalyst. Finally, zwitterionization of the tertiary amine groups in PCD was achieved by treating it with 1,3-propane sultone (1,3-PS) in THF to obtain the desired PCDSs copolymers. The chemical compositions and the structures of PCDSs were confirmed by 1H nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). Additionally, self-assembly behavior in water was systematically investigated for both PCD and PCDSs copolymers. The results showed that these copolymers could form stable, pH-responsive micelles with diameters less than 150 nm via solvent evaporation method while also exhibiting efficient loading and release capabilities for the anti-tumor drug doxorubicin (DOX). Furthermore, cytotoxicity assay revealed low cell cytotoxicity of PCDS micelles towards L929, HeLa, and MCF-7 cells; however DOX-loaded PCDS micelles (PCDS/DOX), particularly those composed of 47% sulfobetaine content exhibited significant inhibitory effects on HeLa and MCF-7 cells along with enhanced cellular uptake efficiency. These findings highlight that pH-responsive zwitterionic sulfobetaine-based polymeric micelles derived from the PCDSs hold great promise for effective DOX delivery.

Polymorphic strategies for encapsulating polyindole@nido-carborane fluorescent polymeric nanocapsules: Their release, imaging, and biological evaluation in the gastrointestinal microenvironment

In this experiment, by combining water-soluble nido-carborane with indole dyes, and used non-toxic and non-irritating sodium alginate and acrylic resin as coating materials to obtain four fluorescent complexes, indol-nido-carborane-sodium alginate- Polymer-A (INS-A) 、indol-nido-carborane-sodium alginate-Polymer-B (INS-B)、indol-nido-carborane-sodium alginate-Polymer-C (INS-C) and indol-nido-carborane-sodium alginate-Polymer-D (INS-D).The transmission electron microscopy (TEM) results showed that the four complexes have different morphologies, with INS-A showing irregular clusters, INS-B being uniformly spherical, INS-C demonstrating a cashew-nut shape and INS-D manifesting a semi-encapsulated state. The spectroscopic properties and in vitro release experiments of the four complexes were performed in different simulated gastrointestinal environments. The results indicated that INS-A and INS-C had excellent photophysical properties and high cumulative release, so INS-A and INS-C were selected for subsequent experiments. Atomic Force Microscope (AFM) test manifested that the surfaces of INS-A and INS-C were relatively smooth. Imaging of HeLa cells with different channels was performed, the Pearson correlation coefficients of both INS-A and INS-C could be calculated to be distributed between 0.21 and 0.60, indicating that the complexes exhibited good imaging performance and could enter the cell and distribute around the nucleus. The results of cell proliferation toxicity (CCK8) experiments showed that at the concentration of 125 μg/mL, the inhibition rates of INS-A and INS-C on HCT-116 and HeLa cells were 47.15 %, 36.70 % and 42.81 %, 35.52 %, respectively, demonstrating that the complexes had an inhibitory effect on cancer cells. In summary, the fluorescent complexes prepared in this paper have good imaging ability and tumor targeting, and are potential fluorescent anticancer reagent.

Preparation and biological evaluation of coumarin amide derivatives bearing fluorine as potential fungicides and anticancer agents

In order to find new potential fungicides and anticancer agents, a series of new coumarin amide derivatives bearing fluorine were synthesized and characterized spectroscopically. Compounds A6, B11, C2 and C7 were confirmed by X-ray diffraction further. The antifungal bioassays against five typical pathogenic fungi showed that compound C5 exhibited more remarkable fungicidal activities against Alternaria alternata (EC50 = 11.5 μg/mL), Colletotrichum gloeosporioides (EC50 = 18.0 μg/mL), Pyricularia grisea (EC50 = 33.8 μg/mL), surpassing kresoxim-methyl. Molecular docking result indicated that C5 displayed high binding affinity to chitinase, which plays crucial role in degradation and remodeling of fungal cell walls. In addition, the anticancer bioassays against three cancer cells demonstrated that compound A4 displayed excellent growth inhibitory effect against Hela cells with IC50 value of 8.13 μM, and low cytotoxicity against human normal cells BEAS-2B. Flow cytometric analysis further demonstrated that A4 significantly arrested cell cycle at the S phase and trigger apoptosis. With the above interesting biological profile, these coumarin derivatives could be used as anfungicides and anticancer candidates.

2-Deoxy-D-Glucose Downregulates Fatty Acid Synthase Gene Expression Via an Endoplasmic Reticulum Stress-Dependent Pathway in HeLa Cells.

Fatty acid synthase (FASN) catalyzes the rate-limiting step of cellular lipogenesis. FASN expression is upregulated in various types of cancer cells, implying that FASN is a potential target for cancer therapy. 2-Deoxy-D-glucose (2-DG) specifically targets cancer cells by inhibiting glycolysis and glucose metabolism, resulting in multiple anticancer effects. However, whether the effects of 2-DG involve lipogenic metabolism remains to be elucidated. We investigated the effect of 2-DG administration on FASN expression in HeLa human cervical cancer cells. 2-DG treatment for 24 h decreased FASN mRNA and protein levels and suppressed the activity of an exogenous rat Fasn promoter. The use of a chemical activator or inhibitors or of a mammalian expression plasmid showed that neither AMPK nor the Sp1 transcription factor is responsible for the inhibitory effect of 2-DG on FASN expression. Administration of thapsigargin, an endoplasmic reticulum (ER) stress inducer, or 4-(2-aminoethyl) benzenesulfonyl fluoride (AEBSF), a site 1 protease inhibitor, mimicked the inhibitory effect of 2-DG on FASN expression. 2-DG did not further decrease FASN expression in the presence of thapsigargin or AEBSF. Site 1 protease mediates activation of ATF6, an ER stress mediator, as well as sterol regulatory element-binding protein 1 (SREBP1), a robust transcription factor for FASN. Administration of 2-DG or thapsigargin for 24 h suppressed activation of ATF6 and SREBP1, as did AEBSF. We speculated that these effects of 2-DG or thapsigargin are due to feedback inhibition via increased GRP78 expression following ER stress. Supporting this, exogenous overexpression of GRP78 in HeLa cells suppressed SREBP1 activation and Fasn promoter activity. These results suggest that 2-DG suppresses FASN expression via an ER stress-dependent pathway, providing new insight into the molecular basis of FASN regulation in cancer.

Design, in silico Evaluation, and Determination of Antitumor Activity of Potential Inhibitors Against Protein Kinases: Application to BCR-ABL Tyrosine Kinase.

Despite significant progress made over the past two decades in the treatment of chronic myeloid leukemia (CML), there is still an unmet need for effective and safe agents to treat patients with resistance and intolerance to the drugs used in clinic. In this work, we designed 2-arylaminopyrimidine amides of isoxazole-3-carboxylic acid, assessed insilico their inhibitory potential against Bcr-Abl tyrosine kinase, and determined their antitumor activity in K562 (CML), HL-60 (acute promyelocytic leukemia), and HeLa (cervical cancer) cells. Based on the analysis of computational and experimental data, three compounds with the antitumor activity against K562 and HL-60 cells were identified. The lead compound efficiently suppressed the growth of these cells, as evidenced by the low IC50 values of 2.8±0.8μM (K562) and 3.5±0.2μM (HL-60). The obtained compounds represent promising basic structures for the design of novel, effective, and safe anticancer drugs able to inhibit the catalytic activity of Bcr-Abl kinase by blocking the ATP-binding site of the enzyme.

Photocytoxicity in vitro studies of ruthenium (II) complexes inducing cell death through targeting DNA

Photodynamic therapy (PDT) has been proven to be an important and effective therapy method with good spatial and temporal accuracy in clinical cancer treatment. Among many PDT candidates, Ru(II)-based compounds have received more attention due to their excellent photochemical and photophysical properties, high singlet oxygen (1O2) photogeneration, and DNA affinities. In this study, three ruthenium(II) complexes (RC1, RC2, RC3) have been designed by varying the aromatic plane area of the main ligand to adjust their 1O2 photogeneration, DNA affinities, DNA photodamage, and photocytoxicity. All complexes display no cytotoxicity in the dark against Hela, A549, HepG2, and BEL-7402 cells. RC1 displays no photocytotoxicity against all tumor cells. RC2 and RC3 showed high photocytotoxicity against BEL-7402 cells. The cellular uptake, cell migration, colonies assay, apoptosis analysis, and cell cycle analysis of RC2 and RC3 confirmed that the ruthenium(II) complexes might effectively enter the cancer cells, and lead to BEL-7402 cells apoptosis through DNA damage pathway. DNA photocleavage, DNA binding, and 1O2 measurement experiments demonstrated the DNA damage caused by RC2 and RC3 under light, compared to RC1, might be due to their high DNA affinities, large 1O2 quantum yields, and large lipophilicity by varying the aromatic plane area of the main ligand. Time dependent density functional theory (TDDFT) calculated results further show that two complexes exhibit the photocytotoxicity possibly via type II photoreaction mechanism because of the larger ΔS-T than O2 and strong SOC between Sn and Tm. Hence, rational design of ruthenium(II) complexes by increasing DNA affinities, 1O2 quantum yields and lipophilicity can be regarded as an effective approach for enhanced photodynamic therapy (PDT).

Multifaceted toxicity assessment of Au, Ag, and TiO2 nanoparticles synthesized by quorum quenching bacterium Salmonella bongori: Impact on bacterial pathogens, cancer cells, mosquitoes, zebrafish, and brine shrimp

The present study pertained to evaluate biological properties of the nanoparticles synthesised using quorum quenching-QQ Salmonella bongori-SB. The QQ potential of SB was confirmed through streaking (halos) and diffusing cell-free-supernatant (decolored) against Chromobacterium violaceum-CV and significant antagonistic effect on Pseudomonas aeruginosa-PA and P. fluorescens-PF. HPLC peaks confirmed the degradation of 3-oxo-C12-HSL (3.185) by QQ-SB at 2.579 and 2.924. The morphological characteristics-(crystallite size; shape with size range), and significant antibacterial-ABA, antibiofilm-ABFA and anti-proliferative-APA (with IC50 values on HeLa and A549 cells) activities of different-NPs were recorded as follows: SB-AuNPs (31.61 nm; aggregated spherical (13.66–18.38 nm)) resulted in good ABA (on PF and Serratia marcescens), ABFA (on PF) and APA (IC50: 33.79 and 33.74 µgmL−1). Similarly, SB-AgNPs (19.83 nm; clustered spherical; 4.81–8.58 nm) showed the most-significant ABA (CV and PF), ABFA (PA, CV and PF) and APA (IC50: 24.57, and 22.7 µgmL−1). Whereas, SB-TiO2NPs (47.33 nm; spherical with 75.13 nm) did not produced significant activities. Overall, the first report on the QQ potential of SB and its NPs emerged to be good candidate that might combat the pragmatic difficulties against MDR strains and drug failures in cancer treatments. Therefore, standardizing its applications in quorum sensing inhibitory mechanisms and anti-proliferative effects is warranted.

Green Synthesis of AgNPs and Fe2O3NPs Using Garlic Plant and Study their Anticancer Activity against Cervical Cancer Cells

In this study, silver and iron nanoparticles were biosynthesized using the garlic plant, an economical and environmentally friendly method. A blend of chitosan (CS) and polyvinylalcohol (PVA) was prepared. The silver nanoparticles (AgNPs), iron oxide nanoparticles (Fe2O3NPs), and the (CS/PVA) blend were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Field Emission Scanning Electron Microscopy (FE-SEM) analyses. The FE-SEM images revealed that Fe2O3NPs were cubical and hexagonal, and AgNPs were spherical aggregates. AgNPs with blend (CS/PVA) and Fe2O3NPs with blend (CS/PVA) and (Fe2O3NPs/blend (CS/PVA) /AgNPs) composite were synthesized and tested for anticancer activity against cervical cancer cells (Hela) using the MTT assay. Best kills and the highest inhibitory effect were observed in (AgNPs/blend (CS/PVA)) and (Fe2O3NPs/Blend (CS/PVA)/AgNPs) composite. These findings demonstrated the method's ability to synthesize nanocomposites with desirable physical, chemical and biological properties. Therefore, these findings demonstrate the new antibacterial and robust cytotoxicity features of the nanocomposite material, which has promising medical applications.