Human Cervical Adenocarcinoma Cells Research Articles

Antitumoral action of carvedilol–a repositioning study of the drug incorporated into mesoporous silica MCM-41

We have studied repositioning of carvedilol (an antihypertensive drug) incorporated into MCM-41 mesoporous silica. The repositioning proposes a reduction in the slow pace of discovery of new drugs, as well as toxicological safety and a significant reduction in high research costs, making it an attractive strategy for researchers and large pharmaceutical companies. We obtained MCM-41 bytemplatesynthesis and functionalized it by post-synthesis grafting with aminopropyltriethoxysilane (APTES) only or with folic acid (FA), which gave MCM-41-APTES and MCM-41-APTES-FA, respectively. We characterized the materials by scanning and transmission electron microscopy, zeta potential (ZP) measurements, Fourier transform infrared absorption spectroscopy, x-ray diffractometry, nitrogen gas adsorption, and CHNS elemental analysis. We quantified the percentage of drug that was incorporated into the MCM-41 materials by thermogravimetric analysis and evaluated their cytotoxic activity in non-tumor human lung fibroblasts and the tumor human melanoma and human cervical adenocarcinoma cell lines by XTT salt reduction (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-arboxanilide). The x-ray diffractograms of the MCM-41 materials displayed low-angle peaks in the 2θrange between 2° and 3°, and the materials presented type IV nitrogen adsorption isotherms and H2 hysteresis typical of the MCM-41hexagonal network. The infrared spectra, the charge changes revealed by ZP measurements, and the CHN ratios obtained from elemental analysis showed that MCM-41 was amino-functionalized, and that carvedilol was incorporated into it. MCM-41-APTES incorporated 23.80% carvedilol, whereas MCM-41 and MCM-41-APTES-FA incorporated 18.69% and 12.71% carvedilol, respectively. Incorporated carvedilol was less cytotoxic to tumor and non-tumor cells than the pure drug. Carvedilol repositioning proved favorable and encourages further studies aimed at reducing its cytotoxicity to non-tumor cells. Such studies may allow for larger carvedilol incorporation into drug carriers or motivate the search for a new drug nanocarrier to optimize the carvedilol antitumoral activity.

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.

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.

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.

Оценка эффективности применения активированной глицирризиновой кислоты у пациенток с ВПЧ-ассоциированными поражениями шейки матки с учетом уровня половых стероидных и гонадотропных пептидных гормонов

Background: the persistence of human papillomavirus (HPV) infection with oncogenic protein expression causes changes in the stratified squamous epithelium, which is the immediate cause of cervical cancer manifestation. The use of the activated glycyrrhizic acid (GA) for HPV-associated cervical lesions is pathogenetically justified. During an experimental study on a culture of human cervical adenocarcinoma cells (HeLa line), it was shown that the antiproliferative effect of GA is enhanced by low concentrations of estradiol and weakened by testosterone. Aim: to evaluate the efficacy of the activated GA in female patients with HPV-associated cervical pathology with respect to the level of sex steroid and gonadotropin-releasing hormones Patients and Methods: a prospective study was conducted with the inclusion of 51 female patients with HPV-associated cervical pathology (ASCUS — atypical squamous epithelial cells of undetermined significance, LSIL — low-grade squamous intraepithelial lesion, HSIL— high-grade squamous intraepithelial lesion according to the Bethesda classification) and the absence of clinical and/or laboratory signs of hyperandrogenism. The following studies were performed: clinical examination, colposcopy, microscopic examination, cytology and immunocytochemistry, as well as hormonal status was evaluated. All female patients received Epigen Intim spray 0.1%, 3 times a day, for 30 days from the moment of inclusion in the study. If indicated, cervical conization was also performed. The treatment efficacy was evaluated 90±7 days after the therapy initiation based on the liquid-based HPV-PAP test results with the determination of p16/Ki67 oncogenic protein co-expression in the cervical epithelium. Changes in the colposcopy results were also evaluated. Results: it was found that the level of estradiol in patients with HSIL was lower versus the patients with ASCUS and LSIL (32 [32.0; 36.0] pg/ml versus 40 [34.5; 45.5] and 40 [33.0; 44.0] pg/ml, respectively, but the difference did not reach statistical significance (p=0.453). 90 days after the follow-up start, according to the cytology results of the cervical epithelium, 50 (98.0%) patients showed the absence of cervical intraepithelial lesions and the absence of p16/Ki67 oncogenic protein co-expression, 48 (94.1%) patients showed no high-risk (HR) HPV DNA, whereas HPV-associated colposcopy signs (anogenital warts, chronic cervicitis signs) persisted only in 6 (11.8%) patients. Conclusion: the use of activated GA in female patients of reproductive age with HPV-associated cervical lesions without clinical and/or laboratory signs of hyperandrogenism allowed to achieve high efficiency indicators: 98.5% — according to the cytology results, 83.3% — in reducing the HR-HPV viral load, 85.7% — in terms of p16/Ki67 oncogenic protein co-expression. KEYWORDS: human papillomavirus, squamous intraepithelial lesion of the cervix, oncogenic protein co-expression, sex steroid hormones, activated glycyrrhizic acid FOR CITATION: Mandrykina Zh.A., Dobrokhotova Yu.E., Ibragimova D.M., Kazieva M.D., Filimonova M.S., Shimanovsky N.L., Akhmetgaliev A.R. Assessment of the activated glycyrrhizic acid efficacy in female patients with HPV-associated cervical lesions with respect to the level of sex steroid and gonadotropin-releasing hormones. Russian Journal of Woman and Child Health. 2024;7(2):127–134 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-7.

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.

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.

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.

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.

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.

Synthesis, substitution kinetics, DNA/BSA binding and cytotoxicity of tridentate N^E^N (E = NH, O, S) pyrazolyl palladium(II) complexes.

The pincer complexes, [Pd(L1)Cl]BF4 (PdL1), [Pd(L2)Cl]BF4 (PdL2), [Pd(L3)Cl]BF4 (PdL3), [Pd(L4)Cl]BF4 (PdL4) were prepared by reacting the corresponding ligands, 2,6-bis[(1H-pyrazol-1-yl)methyl]pyridine (L1), bis[2-(1H-pyrazol-1-yl)ethyl]amine (L2), bis[2-(1H-pyrazol-1-yl)ethyl]ether (L3), and bis[2-(1H-prazol-1-yl)ethyl]sulphide (L4) with [PdCl2(NCMe)]2 in the presence NaBF4. The solid-state structures of complexesPdL1-PdL4 confirmed a tridentate coordination mode, with one chloro ligand completing the coordination sphere to afford square-planar complexes. Chemical behaviour of the complexes in solution confirms their stability in both aqueous and DMSO stock media. The electrochemical properties of the compounds showed irreversible two-electron reduction process. Kinetic reactivity of Pd complexes with the biological nucleophiles viz, thiourea (Tu), L-methionine (L-Met) and guanosine 5'-diphosphate disodium salt (5'-GMP) followed the order: PdL2 < PdL3 < PdL4, and PdL2 < PdL1. The kinetic reactivity is subject to the electronic effects of the spectator ligand(s), and the trend was supported by the DFT computed results. The palladium complexes PdL1-PdL4 bind to calf thymus (CT-DNA) via intercalation mode. In addition, the bovine serum albumin (BSA) showed good binding affinity to the complexes. The mode of quenching mechanism of the intrinsic fluorescence of CT-DNA and BSA by the complexes was found to be static. The order of interactions of the complexes with DNA and BSA was in tandem with the rate of substitution kinetics. The complexes, however, displayed relatively low cytotoxicity (IC50 > 100µM) when tested against the human cervical adenocarcinoma (HeLa) cell line and the transformed human lung fibroblast cell line (MRC-5 SV2).

Suppressive effects of azobenzene-imidazolium ionic conjugates on human cervical adenocarcinoma cells: Effects of alkyl chains and ortho-fluorination

This is the first report of cytotoxic effects of non-fluorinated and difluorinated azobenzene-imidazolium ionic conjugates of varying alkyl chain length in the cationic imidazolium head group were prepared and characterised using FTIR and NMR spectroscopy, and elemental microanalysis. The cytotoxic effects of these ionic conjugates against human cervical adenocarcinoma (HeLa) cells and normal human skin fibroblasts (Hs27) were investigated using the MTT assay. A positive correlation between cytotoxicity and the alkyl chain length in the imidazolium moiety as well as lateral fluorination was observed. In both series, the long homologues (C = 16 and 18) were found to be the most active. All the salts exhibited excellent concentration-dependent cytotoxic effects against HeLa cells. The IC50 values of the non-fluorinated salts ranged between 1.17 µM and 5.43 µM. Fluorination selectively enhanced the cytotoxic potency of azobenzene-imidazolium salts on cancer cells but not on normal Hs27 fibroblasts, wherein for analogues of the same length; the difluorinated salts were relatively more potent and selective. These azobenzene-imidazolium salts could provide insights into preparing alternatives for effective and safe anticancer agents.

Red Wine Inspired Chromophores as Photodynamic Therapy Sensitizers.

Hydroxypyranoflavylium (HPF) cations are synthetic analogs possessing the same basic chromophore as the pyranoanthocyanins that form during the maturation of red wine. HPF cations absorb strongly in the visible spectral region, and most are fluorescent, triplet-sensitize singlet oxygen formation in solution and are strong photooxidants, properties that are desirable in a sensitizer for photodynamic therapy (PDT). The results of this study demonstrate that several simple HPF dyes can indeed function as PDT sensitizers. Of the eight HPF cations investigated in this work, four were phototoxic to a human cervical adenocarcinoma cell line (HeLa) at the 1-10 μmol dm-3 level, while only one of the eight compounds showed noticeable cytotoxicity in the dark. Neither a Type I nor a Type II mechanism can adequately rationalize the differences in phototoxicity of the compounds. Colocalization experiments with the most phototoxic compound demonstrated the affinity of the dye for both the mitochondria and lysosomes of HeLa cells. The fact that relatively modest structural differences, e.g., the exchange of an electron-donating substituent for an electron-withdrawing substituent, can cause profound differences in the phototoxicity, together with the relatively facile synthesis of substituted HPF cations, makes them interesting candidates for further evaluation as PDT sensitizers.

Antitumor and Immunomodulatory Properties of the Bulgarian Endemic Plant Betonica bulgarica Degen et Neič. (Lamiaceae).

Background: Extracts obtained from different Betonica species have been shown to possess important biological properties. The present study aimed to investigate the cytotoxicity, antitumor and immunomodulatory potential of the endemic plant Betonica bulgarica (Lamiaceae) and thus, reveal new aspects of its biological activity. Methods: Methanolic extract obtained from inflorescences was analyzed for cytotoxicity against mammalian cell lines. The antitumor potential of the sample was determined using human cervical and lung adenocarcinoma cells (HeLa and A549). Programmed cell death-inducing effects against HeLa cells and peripheral blood lymphocytes, as well as immunomodulatory properties of the extract were determined by flow cytometry analysis. Results: The research results demonstrated that the extract has significant inhibitory potential against HeLa cells (mean IC50 value 119.2 μg/mL). The sample selectively induced apoptotic death in tumor cells. Cytotoxic effects towards mouse cell lines were detected following treatment with high concentrations of Betonica bulgarica extract (200 and 250 μg/mL). Twenty-four-hour ex vivo incubation of peripheral blood leucocytes in growth medium containing plant extract induced prominent effects in distinct immune cell populations. They included elevated levels of CD25+ and CD56+ T cells’ lymphocytes, particularly CD4+CD25+ and CD8+CD56+ cells. Conclusions: The present study demonstrates that Betonica bulgarica inflorescence extract possesses potential beneficial antitumor and immunomodulatory activity and could serve as a source of bioactive compounds with biomedical application.

Ginsenoside Rg5 Sensitizes Paclitaxel-Resistant Human Cervical-Adeno-Carcinoma Cells to Paclitaxel-And Enhances the Anticancer Effect of Paclitaxel.

In cervical cancer chemotherapy, paclitaxel (PTX) chemoresistance has become a major difficulty, and it also affects the survival rate of numerous tumor patients. Thus, for the reversal of chemoresistance, it is imperative to develop combinatory drugs with petite or almost no side effects to sensitize cells to paclitaxel. Ginsenoside Rg5 (GRg5) may act as a chemosensitizer by reversing multidrug resistance. The present study aimed to determine the potential of GRg5 as a chemosensitizer in PTX-resistant human cervical adeno-carcinoma cell lines (HeLa cells). MTT assay was carried out to assess whether GRg5 can potentiate the cytotoxic effect of PTX in PTX- resistant HeLa cells; using flow cytometry-based annexin V-FITC assay, cellular apoptosis was analyzed; the rate of expression of the cell cycle, apoptosis and major cell-survival-signaling-related genes and its proteins were examined using RT-PCR and Western blotting technique. We found increased mRNA expression of Bak, Bax, Bid, and PUMA genes, whereas the mRNA expression of Bcl2, Bcl-XL, c-IAP-1, and MCL-1 were low; GRg5 combination triggered the efficacy of paclitaxel, which led to increased expression of Bax with an enhanced caspase-9/-3 activation, and apoptosis. Moreover, the study supports GRg5 as an inhibitor of two key signaling proteins, Akt and NF-κB, by which GRg5 augments the susceptibility of cervical cancer cells to PTX chemotherapy. GRg5 drastically potentiated the antiproliferative and pro-apoptotic activity of paclitaxel in PTX-resistant human cervical cancer cells in a synergistic mode. Moreover, in the clinical context, combining paclitaxel with GRg5 may prove to be a new approach for enhancing the efficacy of the paclitaxel.

Core-Sheath-Like Poly(Ethylene Oxide)/Beeswax Composite Fibers Prepared by Single-Spinneret Electrospinning. Antibacterial, Antifungal, and Antitumor Activities.

Composite fibrous materials are prepared from poly(ethylene oxide) (PEO) and beeswax (BW) by single-spinneret electrospinning using chloroform as a common solvent. The obtained fibers have core-sheath-like structure, as evidenced by the water contact angle values and corroborated by the results on the elemental composition of the fiber's surface determined by X-ray photoelectron spectroscopy (XPS) and by analyses with scanning electron microscopy of fibers before and after selective extraction of PEO or BW. Furthermore, the core-sheath-like structure is proven by transmission electron microscopy. This is attributed to self-assembly of BW molecules on the surface of the formed fibers driven by the incompatibility between PEO and BW. 5-Nitro-8-hydroxyquinoline (NQ) is embedded as a model drug with antibacterial, antifungal, and anticancer properties in the PEO/BW fibrous materials. XPS analyses reveal that NQ is present on the surface of the PEO/BW/NQ materials. Using a purposely designed cell for fixation of the fibrous materials the NQ release in phosphate buffer solution with рН 7.4 is followed. The new PEO/BW/NQ fibrous materials exhibit antibacterial activity against S. aureus and E. coli, antifungal effect against C. albicans, and selective anticancer activity against HeLa (human cervical adenocarcinoma cells) and SH-4 (human melanoma cells) cell lines.

A new sesquiterpenoid juvenile hormone III from the stems of Cananga latifolia

A new juvenile hormone III, canangalia I (1), along with six known juvenile hormone III analogues (2–7), was isolated from the methanolic extract of Cananga latifolia stems. All structures were elucidated using spectroscopic data and compared with data from previous literature. Canangalia I (1) was found to be cytotoxic against human cervical adenocarcinoma (HeLa) cells with an IC50 value of 35.00 ± 2.15 µg/ml after 72 h, but was not toxic to Vero cells.