Human Cervical Adenocarcinoma Research Articles

Biocompatible Hybrid Graphenic Thin Coatings on Flexible Substrates through Matrix-Assisted Pulsed Laser Evaporation (MAPLE).

This work reports the production of biocompatible thin layers for biomedical applications based on a graphene-like material (GL), a graphene-related material (GRM) obtained from carbon black. GL was combined in a hybrid fashion with polydopamine (pDA), a mussel-inspired water-resistant wet adhesive bonding obtained by the oxidative polymerization of dopamine (DA), and polyvinyl pyrrolidinone (PVP), a nontoxic synthetic polymer with intrinsic adhesion properties, to obtain a tighter adhesion of the thin layer to the substrate (silicone slices). Matrix-assisted pulsed laser evaporation (MAPLE) was used to coat PDMS slices with thin films of GL-pDA and GL-PVP directly from their frozen suspensions in water. The results indicate that the relevant chemical-physical characteristics of both thin films (evidenced by FTIR and AFM) were maintained after MAPLE deposition and that the films exhibit uniformity also at the nanometric level. After deposition, the GL-pDA and GL-PVP films underwent a biological survey toward murine fibroblasts (NIH3T3), human keratinocytes (HaCAT), and human cervical adenocarcinoma epithelial-like (HeLa) cells to assess the feasibility of this approach. Results indicate that both the GL-pDA and GL-PVP films did not perturb the biological parameters evaluated, including cytoskeleton alterations. Both hybrid films enhanced the effects of GL on cellular vitality across all cell lines. Specifically, the GL-pDA film exhibited a more stable effect over time (up to 72 h), whereas the GL-PVP film behaved similarly to the GL film in NIH3T3 and HeLa cell lines after long-term exposure. These promising results make the GL-pDA and GL-PVP films potential candidates for the manufacture of coated flexible devices for biomedical applications.

Pyrobacteriopheophorbide-a derivatives possessing various hydrophilic esterifying groups at the C17-propionate residues for photodynamic therapy.

Aiming at the application to photodynamic therapy, natural bacteriochlorophyll-a was converted to chemically stable free-base derivatives possessing different kinds of hydrophilic C17-propionate residues. These semi-synthetic bacteriochlorins were found to have self-assembling ability in an aqueous environment and formed stable J-type aggregates in a cell culture medium containing 0.2% DMSO. The electronic absorption spectra of all the sensitizers showed Qy absorption maxima at 754 nm in DMSO as their monomeric states, while a drastic shift of the red-most bands to ca. 880 nm was observed in the aqueous medium. The circular dichroism spectra in the medium showed much intense signals compared to those measured in DMSO, supporting the formation of well-ordered supramolecular structures. By introducing hydrophilic side chains, the bacteriochlorin sensitizers could be dispersed in the aqueous medium as their J-aggregates without the use of any surfactants. Cellular uptake efficiencies as well as photodynamic activities were evaluated using human cervical adenocarcinoma HeLa cells. Among the 11 photosensitizers investigated, the best result was obtained for a charged derivative possessing trimethylammonium terminal (17-CH2CH2COOCH2CH2N+(CH3)3I-) and photocytotoxicity of EC50 = 0.09 μM was achieved by far-red light illumination of 35 J/cm2 from an LED panel (730 nm).

Folic acid-mediated enhancement of the diagnostic potential of luminescent europium-doped hydroxyapatite nanocrystals for cancer biomaging

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.

Synthesis of novel coumarin-triazole hybrids and first evaluation of the 4-phenyl substituted hybrid loaded PLGA nanoparticles delivery system to the anticancer activity

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21. This coumarin derivative-loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, −16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained 21-loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV–vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21-loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21. The IC50 values were determined as IC50 (21-loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml−1 and IC50 (free 21 molecule): 5.74 ± 3.82 mg ml−1 against MCF-7 cells, and as IC50 (21-loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml−1 and IC50 (free 21 molecule): 1.32 ± 0.31 mg ml−1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.

In Vitro Antiviral and Anticancer Effects of Tanacetum sinaicum Essential Oil on Human Cervical and Breast Cancer.

Cervical cancer has been linked to human papillomavirus (HPV) types 16 and 18. Essential oils (EOs) are vital natural products of plants with various therapeutic and biological properties. The purpose of this study is to investigate and assess Tanacetum sinaicum essential oil's possible antiviral and anticancer properties, with a focus on its in vitro effects on human cervical cancer and human breast adenocarcinoma cell lines. Tanacetum sinaicum EO was extracted via hydrodistillation (HD) and characterized using gas chromatography-mass spectrometry (GC-MS). MTT assay was used to determine the cell viability of Hela (a human epithelial cervical cancer) and MCF-7 (human breast adenocarcinoma) cell lines. Quantitative real-time polymerase chain reaction (PCR) was utilized to assess the antiviral efficacy of EO against HPV-16 and 18, and anti-metastatic characteristics. The biological activity of EO was assessed using Autophage and Cell genotoxicity via the comet assay. EO is mostly composed of chrysanthenyl acetate, thujone, and verbenol. The cell viability was reduced after 24 hours of incubation at doses from 100 to 400 µg/ml. Concentrations of 800 to 3,200 µg/ml significantly inhibit cell growth. After a 24-hour incubation period, doses ranging from 100 to 400 µg/ml reduced cell viability from 62 to 72%. Concentrations of 800 to 3,200 µg/ml significantly suppress cell growth by over 95%. In MCF7 and HeLa cell lines, EO lowered virus copy numbers in a dose-dependent manner, with higher concentrations of the oil inhibiting virus replication more effectively. EO treatment increased the number of autophagosomes/autolysosomes and acidic vesicular organelles in both cell lines. On the HeLa and MCF7 cell lines, EO demonstrated antiproliferative and antimetastatic effects. The results demonstrated that EO had dose-dependent genotoxic effects on both cancer cell lines, as evidenced by DNA damage. Tanacetum sinaicum EO is a prospective source of natural bioactive compounds that can be employed in pharmaceutical and medicinal applications due to its antiviral, antiproliferative, anti-metastatic and genotoxic properties.

Anthelminthic and antimicrobial effects of hedge woundwort (Stachys sylvatica L.) growing in Southern Kazakhstan.

The Stachys L. genus has been widely used in traditional medicine in many countries throughout the world. The study aimed to investigate the chemical composition and bioactivity of the hydroethanolic extract (50% v/v) obtained by ultrasonication from the aerial flowering parts of Stachys sylvatica L. (SSE) collected in Almaty region (Southern Kazakhstan). According to RP-HPLC/PDA analysis the leading metabolites of the SSE belonged to polyphenols: chlorogenic acid and its isomers (2.34mg/g dry extract) and luteolin derivatives (1.49mg/g dry extract), while HPLC-ESI-QTOF-MS/MS-based qualitative fingerprinting revealed the presence of 17 metabolites, mainly chlorogenic acid and its isomers, flavonoid glycosides, and verbascoside with its derivatives. GC-MS analysis of the volatile metabolites showed mainly the presence of diterpenoids and fatty acid esters. A reduction in the viability of nematodes Rhabditis sp. was obtained for the SSE concentration of 3.3mg/mL, while 11.1mg/mL showed activity comparable to albendazole. The SSE exhibited higher activity against Gram-positive (MIC = 0.5-2mg/mL) than Gram-negative bacteria and yeast (MIC = 8mg/mL), exerting bactericidal and fungicidal effects but with no sporicidal activity. The SSE showed some antiviral activity against HCoV-229E replicating in MRC-5 and good protection against the cytopathic effect induced by HHV-1 in VERO. The SSE was moderately cytotoxic towards human cervical adenocarcinoma (H1HeLa) cells (CC50 of 0.127mg/mL after 72h). This study provides novel information on the SSE extract composition and its biological activity, especially in the context of the SSE as a promising candidate for further antiparasitic studies.

Enzymatic production process of capric acid-rich structured lipids: Development of formulation as a new therapeutic approach

The present work reports an optimization of the synthesis of MLM-type (medium, long, medium) structured lipids (SL) through an acidolysis reaction of grape seed oil with capric acid catalyzed by Rhizopus oryzae lipase immobilized. At first, tests were carried out by preparing the biocatalysts using enzyme loadings (0.15 to 1 g of enzymatic powder) for each gram of support. Enzyme loading was used 0.3 g of enzymatic powder, and hydrolytic activity of 1860 ± 23.4 IU/g was reached. Optimized conditions determined by the Central Composite Rotatable Design (CCRD) revealed that the acidolysis reaction reached approximately 59 % incorporation degree (%ID) after 24 h, in addition to the fact that the biocatalyst could maintain the incorporation degree in five consecutive cycles. From this high incorporation degree, cell viability assays were performed with murine fibroblast cell lines and human cervical adenocarcinoma cell lines. Concerning the cytotoxicity assays, the concentration of MLM-SL to 1.75 and 2 % v/v were able to induce cell death in 56 % and 64 % of adenocarcinoma cells, respectively. Human cervical adenocarcinoma cells showed greater sensitivity to the induction of cell death when using emulsions with MLM-SL > 1.75 % v/v compared to emulsions with lower content indicating a potential for combating carcinogenic cells.

Salvia officinalis-Hydroxyapatite Nanocomposites with Antibacterial Properties.

In the present study, sage-coated zinc-doped hydroxyapatite was incorporated into a dextran matrix (7ZnHAp-SD), and its physico-chemical and antimicrobial activities were investigated. A 7ZnHAp-SD nanocomposite suspension was obtained using the co-precipitation method. The stability of the nanocomposite suspension was evaluated using ultrasound measurements. The stability parameter calculated relative to double-distilled water as a reference fluid highlights the very good stability of the 7ZnHAp-SD suspension. X-ray diffraction (XRD) experiments were performed to evaluate the characteristic diffraction peak of the hydroxyapatite phase. Valuable information regarding the morphology and chemical composition of 7ZnHAp-SD was obtained via scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) studies. Fourier-transform infrared spectroscopy (FTIR) measurements were performed on the 7ZnHAp-SD suspensions in order to evaluate the functional groups present in the sample. Preliminary studies on the antimicrobial activity of 7ZnHAp-SD suspensions against the standard strains of Staphylococcus aureus 25923 ATCC, Enterococcus faecalis 29212 ATCC, Escherichia coli 25922 ATCC, and Pseudomonas aeruginosa 27853 ATCC were conducted. More than that, preliminary studies on the biocompatibility of 7ZnHAp-SD were conducted using human cervical adenocarcinoma (HeLa) cells, and their results emphasized that the 7ZnHAp-SD sample did not exhibit a toxic effect and did not induce any noticeable changes in the morphological characteristics of HeLa cells. These preliminary results showed that these nanoparticles could be possible candidates for biomedical/antimicrobial applications.

Exploring the Influence of Spacers in EDTA-β-Cyclodextrin Dendrimers: Physicochemical Properties and In Vitro Biological Behavior.

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four β-cyclodextrin (βCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the βCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-βCD platforms and the classical PAMAM-βCD dendrimer. Finally, we determined the toxicity for all EDTA-βCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-βCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

Anticancer effect of novel luteolin capped gold nanoparticles selectively cytotoxic towards human cervical adenocarcinoma HeLa cells: An in vitro approach

BackgroundAlthough luteolin has been confirmed as potent anticancer agent, its potential application as therapeutic is limited by its water solubility. To overcome this shortcoming nanoparticle technology approach was applied. Owing to their proven low toxicity and the possibility to be easily functionalized gold nanoparticles (AuNP) were the nanosystem of choice used in this study. Novel luteolin capped gold nanoparticles (AuNPL) were synthesized and their anticancer effect towards human cervical adenocarcinoma HeLa cells was investigated in vitro. MethodsAuNPL were synthesized by reducing chloroauric acid by trisodium citrate with subsequent addition of luteoline during synthesis and their physicochemical characterization was done. AuNPL cytotoxicity against HeLa, human malignant melanoma A375, and normal human keratinocytes HaCaT cells was tested by MTT cell survival assay, and their IC50 values were determined. The capability of AuNPL to induce cell cycle arrest and apoptosis in HeLa cells were demonstrated by flow cytometry. The antioxidant activity of AuNPL was assessed by DPPH· and ABTS·+ scavenging assays. Cytoprotective properties of AuNPL towards HaCaT cells were examined by measuring the physiological and H2O2 induced intracellular reactive oxygen species (ROS) levels using flow cytometry. Also, genotoxicity of AuNPL in HaCaT cells was investigated by the single cell alkaline comet assay. ResultsSpherical AuNPL, stable in aqueous solution up to six months at 4 °C were obtained in the synthesis. The selectivity in the cytotoxic action of AuNPL on HeLa and A375 cancer cells compared with their cytotoxicity on normal keratinocytes HaCaT was observed. AuNPL exerted their cytotoxic activity against HeLa cells through accumulation of the cells in the subG1 phase of the cell cycle, inducing the apoptotic cell death mediated by the activation of caspase-3 − 8, and − 9. AuNPL antioxidative potential was confirmed by DPPH· and ABTS·+ scavenging assays. IC50 concentration of AuNPL exerted cytoprotective effect against HaCaT cells by the significant reduction of the physiological intracellular ROS level. Additionally, AuNPL were shown as more cytoprotective towards HaCaT cells then luteolin due to the more successful elimination of H2O2 induced intracellular ROS. Moreover, nontoxic concentrations of AuNPL did not cause considerable DNA damage of HaCaT cells, indicating low genotoxicity of the nanoparticles. ConclusionSynthesized AuNPL showed selective cytotoxic activity against HeLa cells, while being nontoxic and cytoprotective against HaCaT cells. The observed findings encourage further investigation of AuNPL as a promising novel anticancer agent.

Cytotoxic activity of Galantamine hydrobromide against HeLa cell line

Cytotoxic activity of Galantamine HBr against human cervical adenocarcinoma cell line HeLa in different concentrations (1.875 μМ ÷ 30 μМ) was evaluated. Inhibition of HeLa cell growth after treatment with Galantamine HBr and index of cell viability were determined. From the experimental results was proven that the drug exerts cytotoxic activity towards HeLa cell line, with antiproliferative activity presented as the value of IC50 = 30 μM ± 0.22.

Zinc(II) Complex with 2-Hydroxy-5-ethylphenylphosponic Acid: Synthesis, Structure, Toxicity, and Accumulation in HeLa Cells

A complex of zinc(II) with 2-hydroxy-5-ethylphenylphosphonic acid (H3L) of the composition [Zn(H2L)2(Н2О)2][Zn(HL)(Н2О)]·H2O (I) was synthesized, the structure of which was established based on data of X-ray diffraction and elemental analysis, quantum chemical calculations, as well as IR and electron absorption spectroscopies. The stability constants of H3L acid complexes with zinc(II) perchlorate in water were determined by potentiometric titration. The cytotoxic properties of H3L acid and complex I were studied for the first time on HeLa cells (human cervical adenocarcinoma). The results on the accumulation of complex I in HeLa cells were obtained by laser confocal microscopy.

BIIB021, an orally available and small-molecule inhibitor of HSP90, activates intrinsic apoptotic pathway in human cervical adenocarcinoma cell line (HeLa).

Heat shock protein 90 (HSP90) is a highly conserved ATP-dependent chaperone protein that plays a vital role in tumorigenesis. This study aims to investigate the apoptosis inducer role of BIIB021 (orally available HSP90 inhibitors) compound via inhibition of HSP90 activity in the human cervical cancer cell line (HeLa). The anticancer potential of BIIB021 was determined by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)] cell proliferation assay against the human cervical cancer cell line (HeLa). ATPase and luciferase aggregation assays were carried out to detect the HSP90 inhibitor potential of BIIB021. To determine the antiproliferative mechanism of the BIIB021, the expression level of the pro-apoptotic and antiapoptotic markers was determined by reverse transcription polymerase chain reaction (RT-PCR) and ELISA experiments. BIIB021 exhibited a cytotoxic effect on HeLa cell proliferation and the inhibitory concentration (IC)50 dose of BIIB021 was found to be 14.79 nM at 48 h. BIIB021 decreased the ATP hydrolysis rate of HSP90 and blocked the refolding of the desaturated luciferase in the presence of ATP. To understand the antiproliferative mechanism of the BIIB021 in HeLa cells, the mRNA and protein expression levels of the apoptotic markers [BCL-2 associated X (BAX), B-cell lymphoma 2 (BCL-2), cytochrome-c (CYT-c), and caspase-3 (CAS-3)] were determined by RT-PCR and ELISA experiments. The results obtained indicated that BIIB021 decreased BCL-2 levels and increased BAX, CYT-c, and CAS-3 levels in human cervical cancer cells. These results confirmed that BIIB021 inhibited the chaperone activity of HSP90, resulting in anti-proliferating effects in cervical cancer cells via the induction of the intrinsic apoptotic pathways.

Radixin modulates the plasma membrane localization of CD47 in human uterine cervical adenocarcinoma cells

Despite the dramatic success of immune checkpoint blockers in treating numerous cancer cell types, current therapeutic modalities provide clinical benefits to a subset of patients with cervical cancers. CD47 is commonly overexpressed in a broad variety of cancer cells, correlates with poor clinical prognosis, and acts as a dominant macrophage checkpoint by interacting with receptors expressed on macrophages. It allows cancer cells to escape from the innate immune system and hence is a potential therapeutic target for developing novel macrophage checkpoint blockade immunotherapies. As the intracellular scaffold proteins, ezrin/radixin/moesin (ERM) family proteins post-translationally regulate the cellular membrane localization of numerous transmembrane proteins, by crosslinking them with the actin cytoskeleton. We demonstrated that radixin modulates the plasma membrane localization and functionality of CD47 in HeLa cells. Immunofluorescence analysis and co-immunoprecipitation assay using anti-CD47 antibody showed the colocalization of CD47 and all three ERM families in the plasma membrane, and the molecular interactions between CD47 and all three ERM. Interestingly, gene silencing of only radixin, reduced the CD47 plasma membrane localization and functionality by means of flow cytometry and phagocytosis assay but had little influence on its mRNA expression. Together, in HeLa cells radixin may function as a principal scaffold protein responsible for the CD47 plasma membrane localization.

Copper(II) сomplexes with 2-hydrохy-5-ethylphenylphosphosphonic acid: synthesis, structure, cytotoxicity, and accumulation in HeLa cells

In order to study the physicochemical and biological properties of the coordination compounds of bioactive metal ions with 2-hydroxyphenylphosphonic acid derivatives, the reaction of 2-hydroxy-5-ethylphenylphosphonic acid (Н3L1) with copper(II) perchlorate, sulfate, nitrate, and acetate in water was studied for the first time. It has been established that, regardless of the ratio of reagents, in the case of copper(II) perchlorate, sulfate, and nitrate, a complex of the composition [Cu(H2L1)2(Н2О)2] is formed in high yield, while in the case of using copper(II) acetate a complex [Cu(HL1)(H2O)2] is formed, the composition of which is established on the basis of a combination of elemental analysis data, IR and electronic spectra. Quantum-chemical calculations of the structure of [Cu(H2L1)2(H2O)2] and [Cu(HL1)(H2O)2] complexes were performed for the first time by the density functional theory (DFT) method. The cytotoxic properties of H3L1 acid and copper complexes [Cu(HL1)(H2O)2] and [Cu(H2L1)2(H2O)2] with respect to HeLa tumor cells of human cervical adenocarcinoma were studied. The accumulation of the resulting copper(II) complexes in HeLa cells was proved by laser confocal microscopy.

Synthesis of Brominated Lactones Related to Mycalin A: Selective Antiproliferative Activity on Metastatic Melanoma Cells and Inhibition of the Cell Migration.

Starting from D-xylonolactone and D-ribonolactone, several five-membered bromolactones, related to the C1-C5 portion of mycalin A lactone, have been synthesized. The bromination of D-ribonolactone with HBr/AcOH, without a subsequent transesterification step, has been studied for the first time, giving us most of the acetylated lactones investigated in the present study. For each compound, where possible, both the C-3 alcohol and the corresponding acetate were prepared. Evaluation of their anti-tumor activity showed that all the acetates possess a good cytotoxicity towards human melanoma (A375), human cervical adenocarcinoma (HeLa) and human metastatic melanoma (WM266) cancer cells, comparable or even higher than that displayed by the original mycalin A lactone. Lactone acetates derived from D-ribonolactone showed the higher selectivity of action, exhibiting a strong cytotoxicity on all the tested tumor cells but only a limited toxicity on healthy human dermal fibroblast (HDF) cells, used as a control. Wound healing assays showed that two of these substances inhibit the migration of the WM266 cells.

Biogenic Synthesis of Silver Nanoparticles using Lasiosiphon eriocephalus (Decne): In vitro Assessment of their Antioxidant, Antimicrobial and Cytotoxic Activities.

The emergence of novel nanobiomedicine has transformed the management of various infectious as well as non-infectious diseases.Lasiosiphon eriocephalus, a medicinal plant, revealed the presence of active secondary metabolites and biological potentials. The present study was aimed to demonstrate the biosynthesis of silver nanoparticles using L. eriocephalus leaf extract (LE-AgNPs) and their biological properties, such as antioxidant, antibacterial and anticancer potential. The biosynthesized LE-AgNPs were characterized by UV-Visible spectroscopy, Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR) analysis. The antibacterial activity was checked by minimum inhibitory concentration (MIC) and zone of inhibition assays against Gram-positive and Gram-negative bacteria. The anticancer potential of biogenic LE-AgNPs was checked by cytotoxicity and genotoxicity assay against human cervical adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cells. UV-visible spectroscopy confirmed the formation of silver nanoparticles by measuring the surface plasmon resonance peak of the colloidal solution at 410-440 nm. The results of SEM and TEM revealed the distribution and spherical shape of 20-50 nm sized AgNPs. XRD spectrum confirmed the characteristic peaks at the lattice planes 110, 111, 200, 220 and 311 of silver which confirmed the crystalline nature of biosynthesized LE-AgNPs. FTIR spectrum of plant extract and biogenic LE-AgNPs was recorded in between 1635-3320 cm-1 which confirmed stretching vibrations of possible functional groups C=C and O-H, responsible for the reduction of silver ions to silver nanoparticles. The in vitro antioxidant potential of LE-AgNPs was evaluated using DPPH (IC50 = 26.51 ± 1.15 μg/mL) and ABTS radical assays (IC50 =74.33 ± 2.47 μg/mL). The potential antibacterial effects of LE-AgNPs confirmed that 92.38 ± 2.70% growth inhibition occurred in E. coli in response to 0.1mg/mL concentration of LE-AgNPs followed by P. aeruginosa (75.51 ± 0.76), S. aureus (74.53 ± 1.26) and K. pneumoniae (67.4 ± 3.49). The cytotoxicity results interpreted that the biogenic silver nanoparticles exhibited strong dose and time dependent cytotoxicity effect against selected cancer cell lines where IC50 concentration of LE-AgNPs required to inhibit the growth of HeLa cells after 24 h exposure was 4.14 μg/mL and MCF7 cells 3.00 μg/mL, respectively. Significant DNA fragmentation was seen in the DNA extracted from HeLa and MCF-7 cells exposed to more than 2.5 to 10 μg/mL concentrations of LE-AgNPs. The overall findings from the present investigation indicated that the AgNPs synthesized using L. eriocephalus exerted strong biological potentials such as antioxidant, antimicrobial and extensive cytotoxicity and genotoxicity activities.

Betaxanthin Profiling in Relation to the Biological Activities of Red and Yellow Beta vulgaris L. Extracts.

Beta vulgaris L. is an edible plant with health-beneficial activities. The profile of betaxanthins is more complex than previously described in beetroot cultivars. Twenty-four betaxanthins were detected in extracts of the peel and flesh of five cultivars by HPLC-DAD-ESI-MS, of which two new betaxanthins (arginine-Bx and ornithine-Bx) were detected for the first time in B. vulgaris cultivars. The content of betaxanthins in the studied cultivars decreased in the Tytus > Ceryl > Chrobry > Forono > Boldor sequence. The highest content of compounds (1231 mg/100 g DE) was observed in the Tytus cultivar (peel). The peel of B. vulgaris, which is often considered a waste, appeared to be a richer source of betaxanthins compared to its flesh. Antibacterial and antifungal activities were determined against twenty-three microorganisms. Tytus (peel) showed a moderate or good bactericidal effect, especially against the majority of Gram-positive bacteria as well as against most of the tested fungi (MIC = 0.125-0.5 mg/mL) and additionally characterized by low cytotoxicity towards non-cancerous cells (CC50 = 405 μg/mL, CC50-50% cytotoxic concentration). Tytus flesh also showed a high cytotoxicity value against human cervical adenocarcinoma (HeLa), with CC50 of 282 μg/mL. Correlation analysis was used to determine the relationship between the betaxanthin profiles and antimicrobial and anticancer activities. Arginine-Bx, proline-Bx, and tryptophan-Bx were indicated as active against HeLa and the colon cancer cell line (RKO), while asparagine-Bx and phenylalanine-Bx was responsible for activity against all tested bacterial and yeast species. The significant effectiveness and safety of these beetroots make indicated compounds promising applicants as antimicrobial and anticancer agents.

Chlorambucil-Loaded Graphene-Oxide-Based Nano-Vesicles for Cancer Therapy.

In this study, the authors have designed biocompatible nano-vesicles using graphene oxide (GO) for the release of chlorambucil (CHL) drugs targeting cancerous cells. The GO sheets were first sulfonated and conjugated with folic acid (FA) molecules for controlled release and high loading efficiency of CHL. The chlorambucil (CHL) drug loading onto the functionalized GO surface was performed through π-π stacking and hydrophobic interactions with the aromatic planes of GO. The drug loading and "in vitro" release from the nano-vesicles at different pH were studied. The average particle size, absorption, and loading efficiency (%) of FA-conjugated GO sheets (CHL-GO) were observed to be 300 nm, 58%, and 77%, respectively. The drug release study at different pH (i.e., 7.4 and 5.5) showed a slight deceleration at pH 7.4 over pH 5.5. The amount of drug released was very small at pH 7.4 in the first hour which progressively increased to 24% after 8 h. The rate of drug release was faster at pH 5.5; initially, 16% to 27% in the first 3 h, and finally it reached 73% after 9 h. These observations indicate that the drug is released more rapidly at acidic pH with a larger amount of drug-loading ability. The rate of drug release from the CHL-loaded GO was 25% and 75% after 24 h. The biotoxicity study in terms of % cell viability of CHL-free and CHL-loaded GO against human cervical adenocarcinoma cell line was found to have lower cytotoxicity of CHL-loaded nano-vesicles (IC50 = 18 μM) as compared to CHL-free (IC50 = 8 μM). It is concluded that a high drug-loading efficiency and controlled release with excellent biotoxicity of CHL-GO offers an excellent application in the biomedical field.

Metabolic profiling of Ochradenus baccatus Delile. utilizing UHPLC-HRESIMS in relation to the in vitro biological investigations

Ochradenus baccatus Delile (Resedaceae) is a desert plant with edible fruits native to the Middle East. Few investigators have reported antibacterial, antiparasitic and anti-cancer activities of the plant. Herein we evaluated the cytotoxic activity of O. baccatus using four cell lines and a zebrafish embryo model. Additionally, liquid chromatography coupled with mass spectroscopy was performed to characterize the extract’s main constituents. The highest cytotoxicity was observed against human cervical adenocarcinoma (HeLa), with CC50 of 39.1 µg/mL and a selectivity index (SI) of 7.23 (p < 0.01). Metabolic analysis of the extract resulted in the annotation of 57 metabolites, including fatty acids, flavonoids, glucosinolates, nitrile glycosides, in addition to organic acids. The extract showed an abundance of hydroxylated fatty acids (16 peaks). Further, 3 nitrile glycosides have been identified for the first time in Ochradenus sp., in addition to 2 glucosinolates. These identified phytochemicals may partially explain the cytotoxic activity of the extract. We propose O. baccatus as a possible safe food source for further utilization to partially contribute to the increasing food demand specially in Saharan countries.