Human Cervical Epithelioid Carcinoma Research Articles

A Study on the Biological Activity of Optically Pure Aziridine Phosphines and Phosphine Oxides.

A series of optically pure aziridine phosphines and their corresponding phosphine oxides were synthesized through established chemical methodologies. The compounds were systematically investigated for their biological properties. Notably, all synthesized compounds demonstrated moderate antibacterial activity only against the reference strain of Staphylococcus aureus. However, compounds 5 and 7 exhibited noteworthy cell viability inhibition of human cervical epithelioid carcinoma HeLa cells and endometrial adenocarcinoma Ishikawa cells. Further studies of these compounds revealed additional biological effects, including disruption of the cell membrane in high concentrations, cell cycle arrest in the S phase, and the induction of reactive oxygen species (ROS). Comparative analysis of the two classes of chiral organophosphorus derivatives of aziridines indicated that chiral phosphine oxides displayed significantly higher biological activity. Consequently, these findings suggest that chiral phosphine oxides may be potential candidates for the development of anticancer drugs. In light of the significant interest in preparations whose structure is based on a three-membered aziridine ring in terms of potential anticancer therapy, this research fits into the current research trend and should constitute a valuable addition to the current state of knowledge and the existing library of aziridine derivatives with anticancer properties.

A facile heterogeneous catalytic approach for one-pot synthesis of fused benzoxazinones using Cuβ zeolite and Evaluation of biological activities

A simple heterogeneous catalytic process has been established for the single-step synthesis of fused benzoxazinones, quinazolinones, and thiadazines through Markownikoff's hydroamination followed by intramolecular cyclization using Cuβ zeolite. The probability and limitations of this catalytic approach were explored using various substrates. The efficiency and feasibility of scaling up the current catalytic system were demonstrated through gram-scale experiments. Moreover, the catalyst was reused for up to five cycles with no noticeable decrease in its catalytic effectiveness. Furthermore, the synthesized compounds were subjected to in vitro assessment to determine their potential as anticancer agents against human cervical epithelioid carcinoma (HeLa), mouse breast cancer (4T-1), and human lung adenocarcinoma (A-549) cell lines. Cytotoxicity studies revealed that 3f, 3b′, 3d′, and 3g′ compounds exhibit anti-cancer activity against breast, cervical and lung cancer cells. Additionally, their antimicrobial activity against bacteria and yeast was also evaluated. The compound 3i exhibited superior antifungal activity against Candida albicans.

Evaluation of anticancer, antimicrobial, and antioxidant activities of rosemary (Rosmarinus Officinalis) essential oil and its Nanoemulgel

Throughout history, natural herbal medicines have been used to treat a wide range of serious diseases. This study aimed to develop rosemary oil into a nanoemulgel and evaluate its antimicrobial and anticancer activities. Rosmarinus officinalis (R. officinalis) oil was developed into a nanoemulgel by using a self-nanoemulsifying technique with Tween 80 and Span 80. The hydrogel (Carbopol 940) was then incorporated into the nanoemulsion and mixed well. After this, the antioxidant activity of the R. officinalis oil was measured and its nanoemulgel droplet size, polydispersity index (PDI), rheology, antimicrobial effect, and cytotoxic activity were investigated. The optimum formulation (50% Tween, 15% Span 80, and 35% R. officinalis oil) was used to create the best nanoemulsion, that had droplet size of 159.23 ±1.22 nm and 0.206 ±0.08 PDI. R. officinalis showed strong antioxidant activity, with 22.38 ±0.7 μg/mL when compared to trolox (2.7 ±0.5 μg/mL). Interesting results were obtained with the nanoemulgel against different types of bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Methicillin-resistant staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 2.3, 3.75, and 6.5 µg/mL, respectively. In addition, the half-maximal inhibitory concentration (IC50) of the nanoemulgel when applying it to human hepatocellular carcinoma cells (Hep3B) and human cervical epithelioid carcinoma cells (HeLa) was 28.84, 28.18, and 24.54 µg/mL, respectively, which demonstrated that the nanoemulgel has anticancer effects. In conclusion, R. officinalis oil nanoemulgel would be a promising novel dosage form for pharmaceutical industries to be used for the treatment of different cancer cell lines and microbial infections.

In vitro cytotoxic activity of Verbascum alceoides against cervix carcinoma cells

Background: Verbascum species showed various pharmacological activities including anti-inflammatory, antitussive, antiulcerogenic, immunomodulatory, antimicrobial, antimalarial, antioxidant, and anticancer activities. Objectives: The aim of this work was to evaluate cytotoxicity of different fractions of Verbascum alceoides, which belongs to this genus. Materials and Methods: Aerial parts of this plant were collected from Doveiseh area in Kordestan province. The plant was extracted using a four-step extraction method with increasing solvent polarity (i.e., hexane, dichloromethane, chloroform-methanol [9:1], and methanol). The methanol extract was finally separated between water and butanol. Hexane, dichloromethane, chloroform-methanol, butanol, and aqueous partitions were then subjected to cytotoxicity evaluation. Showing the most potent cytotoxic effects, the butanolic partition was further fractionated by medium-performance liquid chromatography and similar eluates were pooled to prepare five final butanolic fractions, named A–E. Results: In vitro cytotoxicity of these fractions against human cervical epithelioid carcinoma (HeLa) and human umbilical vein endothelial cell (HUVEC) was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Fractions D, E, and A showed a significant and dose-dependent inhibition of cell proliferation (half maximal inhibitory concentration [IC50] of 30, 39.8, and 188.6 µg/mL, respectively). According to the preliminary thin-layer chromatography analysis, these cytotoxic effects may be mainly due to presence of saponin and flavonoid compounds. Conclusion: Future studies will be aimed to isolate and purify active constituents and investigate the effect of them on more different kinds of cancer cells.

Cultivar-Dependent Anticancer and Antibacterial Properties of Silver Nanoparticles Synthesized Using Leaves of Different Olea Europaea Trees

The green synthesis of nanoparticles (NPs) is currently under worldwide investigation as an eco-friendly alternative to traditional routes (NPs): the absence of toxic solvents and catalysts make it suitable in the design of promising nanomaterials for nanomedicine applications. In this work, we used the extracts collected from leaves of two cultivars (Leccino and Carolea) belonging to the species Olea Europaea, to synthesize silver NPs (AgNPs) in different pH conditions and low temperature. NPs underwent full morphological characterization with the aim to define a suitable protocol to obtain a monodispersed population of AgNPs. Afterwards, to validate the reproducibility of the mentioned synthetic procedure, we moved on to another Mediterranean plant, the Laurus Nobilis. Interestingly, the NPs obtained using the two olive cultivars produced NPs with different shape and size, strictly depending on the cultivar selected and pH. Furthermore, the potential ability to inhibit the growth of two woman cancer cells (breast adenocarcinoma cells, MCF-7 and human cervical epithelioid carcinoma, HeLa) were assessed for these AgNPs, as well as their capability to mitigate the bacteria concentration in samples of contaminated well water. Our results showed that toxicity was stronger when MCF-7 and Hela cells were exposed to AgNPs derived from Carolea obtained at pH 7 presenting irregular shape; on the other hand, greater antibacterial effect was revealed using AgNPs obtained at pH 8 (smaller and monodispersed) on well water, enriched with bacteria and coliforms.

Analysis and evaluation of the antimicrobial and anticancer activities of the essential oil isolated from Foeniculum vulgare from Hamedan, Iran

In this study, biological properties of the essential oil isolated from seeds of Foeniculum vulgare (F. vulgare) were evaluated. GC-MS analysis revealed Trans-Anethole (80.63%), L-Fenchone (11.57%), Estragole (3.67%) and Limonene (2.68%) were the major compounds of the essential oil. Antibacterial activity of the essential oil against nine Gram-positive and Gram-negative strains was studied using disc diffusion and micro-well dilution assays. Essential oil exhibited the antibacterial activity against three Gram-negative strains of Pseudomonas aeruginosa, Escherichia coli, and Shigella dysenteriae. The preliminary study on toxicity of seed oil was performed using Brine Shrimp lethality test (BSLT). Results indicated the high toxicity effect of essential oil (LC50 = 10 μg/mL). In vitro anticancer activity of seed oil was investigated against human breast cancer (MDA-Mb) and cervical epithelioid carcinoma (Hela) cell lines by MTT assay. Results showed the seed oil behave as a very potent anticancer agent with IC50 of lower than 10 μg/mL in both cases.

Induction of apoptosis in HeLa cancer cells by an ultrasonic-mediated synthesis of curcumin-loaded chitosan-alginate-STPP nanoparticles.

Natural herbal compounds have been widely introduced as an alternative therapeutic approach in cancer therapy. Despite potent anticancer activity of curcumin, its clinical application has been limited because of low water solubility and resulting poor bioavailability. In this study, we designed a novel ultrasonic-assisted method for the synthesis of curcumin-loaded chitosan–alginate–sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). Furthermore, antitumor effect of curcumin-loaded NPs was evaluated in vitro. Field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) were used to characterize the properties of NPs. Antitumor activity of curcumin-loaded NPs was assessed by using MTT and quantitative real-time polymerase chain reaction (qRT-PCR). FE-SEM and AFM data revealed the spherical morphology, and the average size of NPs was <50 nm. In vitro cytotoxicity assay suggested that curcumin-loaded CS-ALG-STPP NPs displayed significant antitumor activity compared with the free curcumin. Gene expression level analyses showed that curcumin NPs significantly increased the apoptotic gene expression. Collectively, our results suggest that curcumin-loaded NPs significantly suppressed proliferation and promoted the induction of apoptosis in human cervical epithelioid carcinoma cancer cells, which might be regarded as an effective alternative strategy for cancer therapy.

Photophysical, Cellular‐Uptake, and Bioimaging Studies of Luminescent Ruthenium(II)–Polypyridine Complexes Containing a d‐Fructose Pendant

Two luminescent ruthenium(II)–polypyridine complexes, appended with a d‐fructose unit, [Ru(N^N)2(bpy‐fructose)](PF6)2 [bpy‐fructose = 4‐(1‐deoxy‐d‐fructos‐1‐yl)aminocarbonyl‐4′‐methyl‐2,2′‐bipyridine; N^N = 4,7‐diphenyl‐1,10‐phenanthroline (Ph2‐phen) (1a) and 2,2′‐bipyridine (bpy) (2a)] and their d‐fructose‐free counterparts [Ru(N^N)2(bpy‐Et)](PF6)2 [bpy‐Et = 4‐(ethylaminocarbonyl)‐4′‐methyl‐2,2′‐bipyridine; N^N = Ph2‐phen (1b) and bpy (2b)] are synthesized and characterized. The photophysical properties, lipophilicity, cytotoxicity, and cellular uptake of the complexes are studied. Laser‐scanning confocal microscopy reveals that both complexes 1a and 1b display intense membrane staining toward human breast adenocarcinoma (MCF‐7) cells. However, while complex 1a retains its membrane‐staining characteristic when incubated with human cervical epithelioid carcinoma (HeLa) cells, complex 1b is localized in the mitochondria. Additionally, fructose‐dependent cellular‐uptake experiments suggest that complex 1a is transported into MCF‐7 cells through a glucose transporter (GLUT) mediated pathway.

Normonanchocidins G and H, New Pentacyclic Guanidine Alkaloids from the Far-Eastern Marine Sponge Monanchora pulchra

Two new pentacyclic guanidine alkaloids, normonanchocidins G (1) and H (2) containing an unusual ω-2-hydroxy fatty acid moiety were isolated from the Far-Eastern marine sponge Monanchora pulchra. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopic and mass spectrometric data interpretation. Compounds 1 and 2 exhibit potent cytotoxic activities against human leukemia THP-1, HL-60 cells, human cervical epithelioid carcinoma HeLa cells and also have high impact on ability of HeLa cells to migrate.

Bioactivity evaluation of cudraxanthone I, neocyclomorusin and (9βh)-3β-acetoxylanosta-7,24-diene isolated from Milicia excelsa Welw. C. C. Berg (Moraceae)

This study aimed to investigate the cytotoxic, antioxidant, and antimicrobial activities of three compounds isolated from the methanolic extract of the roots bark of Milicia excelsa (Moraceace) namely cudraxanthone I (1), neocyclomorusin (2) and (9βH)-3β-acetoxylanosta-7,24-diene (3). The cytotoxic activities of the compounds were determined using the xCELLigence system (Real Time Cell Analyzer). The compounds of cudraxanthone I and neocyclomorusin exhibited the excellent cytotoxic effects on the growth of human cervical epithelioid carcinoma (HeLa) cell lines (IC50 < 10 µg/mL). Among the compounds; neocyclomorusin showed the highest radical scavenging activity (IC50 = 0.73 ± 0.01 mg/mL). The compounds exhibited low antimicrobial activity against Staphylococcus aureus ATCC 25923. This study supports the documented medicinal effects of the compounds and opens up the possibilities of pharmaceutical applications.

Inhibitory Effects of the Active Components Isolated from Satureja Boissieri Hausskn. Ex Boiss. On Human Cervical Cancer Cell Line

The aim of this study was to isolate the active components from the essential oil (EO) of Satureja boissieri and to investigate the cytotoxic effects of these components on human cervical epithelioid carcinoma (HeLa) cell line. The major components of EO were found to be p-cymene (23.15%), γ-terpinene (22.84%), thymol (18.96%) and carvacrol (21.25%) using GC-MS. The components were separated by column chromatography and p-cymene, thymol and spathulenol were isolated as pure terpenoids. The cytotoxic activity of the components was investigated using the xCELLigence system (Real Time Cell Analyzer). The pure compounds, p-cymene and thymol exhibited excellent cytotoxic effects against HeLa cell line. Practical Applications Satureja boissieri Hausskn. ex Boiss.(Lamiaceae) is known as Catri/Kekik and used as a condiment and herbal tea in the kitchen of local people in Turkey. The genus Satureja has therapeutic properties because of its high amounts of active components such as thymol, carvacrol, p-cymene and γ-terpinene. The results demonstrated that S. boissieri and its active components may be suggested as a promising natural agents for alleviating human cervical epithelioid carcinoma cell growth.

5′-Norcarbocyclic analogues of furano[2,3-d]pyrimidine nucleosides

Abstract 5′-Norcarbocyclic analogues of furano[2,3-d]pyrimidine nucleosides as well as 5-bromo and 5-iodouracil derivatives were synthesized to evaluate their potential antitumor activity. The halogenated derivatives display no cytotoxicity with respect to all tested cells: KB-3-1 (human epidermoid carcinoma), HeLa (human cervical epithelioid carcinoma), HuTu-80 (human duodenal cancer), B16 (mouse melanoma), and MDCK (normal epithelial). The cytotoxicity of the non-halogenated furano[2,3-d]pyrimidine derivatives increases with the lengthening of the alkyl chain of the substituent from 45 to 60 μm for octyl to from 3 to 10 μm for dodecyl.

Synthesis, cytotoxic activity, and computational analysis of N10-substituted acridone analogs

A series of twenty N10-substituted acridone derivatives were synthesized, tested for in vitro cytotoxic activity, and analyzed computationally to predict their multi-drug resistance (MDR) modulation potential. All synthesized N10-substituted acridone analogs were tested for their in vitro cytotoxic activity against human breast adenocarcinoma (MCF-7), human small cell lung carcinoma (A-549), human colon adenocarcinoma (HT-29), and human cervical epithelioid carcinoma (HeLa) cell lines by MTT assay. The compounds were observed to be inactive against the HT-29 cell line. Among the synthesized compounds, compound 14 showed good in vitro activity against MCF-7, A-549, and HeLa cancer cell lines in the low micromolar (µM) range as compared to other compounds. Additionally, in silico study was performed to check the multi-drug resistance modulator (MDR) effect of these compounds using docking simulations in the ATP binding site of P-gp. The results of docking simulation displayed important interactions of molecules 6, 7, 13, 14, 19, and 20 in the active site of this protein and proposed their dual action, i.e., anti-cancer and MDR modulation.

Phosphinogold(I) dithiocarbamate complexes: effect of the nature of phosphine ligand on anticancer properties.

The reactions of potassium salts of the dithiocarbamates L {where L = pyrazolyldithiocarbamate (L1), 3,5-dimethylpyrazolyldithiocarbamate (L2), or indazolyldithiocarbamate (L3)} with the gold precursors [AuCl(PPh3)], [Au2Cl2(dppe)], [Au2Cl2(dppp)], or [Au2Cl2(dpph)] lead to the new gold(I) complexes [AuL(PPh3)] (1–3), [Au2L2(dppe)] (4–6), [(Au2L2)(dppp)] (7–9), and [Au2(L)2(dpph)] (10–12) {where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, and dpph = 1,6-bis(diphenylphosphino)hexane}. These gold compounds were characterized by a combination of NMR and infrared spectroscopy, microanalysis, and mass spectrometry; and in selected cases by single-crystal X-ray crystallography. Compounds 4–6, which have dppe ligands, are unstable in solution for prolonged periods, with 4 readily transforming to the Au18 cluster [Au18S8(dppe)6]Cl2 (4a) in dichloromethane. Compounds 1–3 and 7–12 are all active against human cervical epithelioid carcinoma (HeLa) cells, but the most active compounds are 10 and 11, with IC50 values of 0.51 μM and 0.14 μM, respectively. Compounds 10 and 11 are more selective toward HeLa cells than they are toward normal cells, with selectivities of 25.0 and 70.5, respectively. Further tests, utilizing the 60-cell-line Developmental Therapeutics Program at the National Cancer Institute (U.S.A.), showed 10 and 11 to be active against nine other types of cancers.

Novel synthesis of palladium (II) complexes derived from 3-arylsydnone-4-carbaldehyde N(4)-phenylthiosemicarbazones and biological activity

The aim of this research is to investigate whether the oxygen atom O(6) in the sydnone ring of 3-arylsydnone-4-carbaldehyde N(4)-phenylthiosemicarbazones (HArSYTSCs, 3a-d) is a good electron donor atom upon metal complexation. Furthermore, ligands 3a-d and the corresponding palladium complexes (Pd(ArSYTSC)Cl, 4a-d) would be expected to find their potent biological activities. The desired palladium complexes 4a-d were first synthesized from thiosemicarbazones 3a-d. Then, the antiproliferative activity of ligands 3a-d and complexes 4a-d were tested against human hepatocellular carcinoma and human cervical epithelioid carcinoma (HeLa) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trazolium bromide (MTT) assay. According to X-ray analyses, ligands 3a-d are bonded to the Pd (II) center in an O, N, S-tridentate coordination mode through sydnone carbonyl oxygen O(6), azomethine nitrogen and the thiolate sulfur atom. The carbonyl oxygen of the sydnone ring is found to be a good electron donor site upon metal complexation. Moreover, MTT assay results reveal that the palladium complexes 4a-d have greater antiproliferative activity than 5-fluorouracil. In particular, the complexes exhibit obvious better activity than the corresponding ligands 3a-d against HeLa cell. The results indicate that the synthesized novel palladium complexes have greater antiproliferative activity than both 5-fluorouracil and the corresponding ligands against HeLa cell. Accordingly, the study of sydnonyl complexes bearing anticancer activities may support the development of coordination chemistry.

Synthesis and antiproliferative activity of helonioside A, 3′,4′,6′-tri-O-feruloylsucrose, lapathoside C and their analogs

The first total synthesis of natural phenylpropanoid sucrose esters (PSEs) helonioside A 1, 3′,4′,6′-tri-O-feruloylsucrose 2 and lapathoside C 3 along with 17 unnatural PSE analogs has been successfully accomplished in a short and simple synthetic route. A selected set of 17 synthesized PSEs were evaluated for the antiproliferative activity against human cervical epithelioid carcinoma (HeLa) cell lines using MTS assay method. Eleven (11) compounds showed significant antiproliferative activity with their IC50values ranging from 0.16 to 6.01 μM. The structure–activity-relationship studies revealed that the antiproliferative activity is influenced by the lipophilicity and number of feruloyl substituents on these compounds. The preliminary screening indicated that these compounds are potentially very valuable source for new lead chemotherapeutics.

Effect of Cell Position on Impedance Measurement in Microfluidic Channel with Planar Microelectrodes and a Three-Pillar Structure

Impedance analysis of single cells offers the possibility of obtaining accurate, reliable, and in-depth information about their pathological condition. In this work, we present the physical capture of a single cell using a microfluidic device with a three-pillar microstructure, impedance measurement using a set of planar microelectrodes, and the derivation of an electrical model that fits the experimental results. The relationship between impedance characteristics and the location of a single HeLa cell (human cervical epithelioid carcinoma) is investigated by impedance spectroscopy. When a single cell fell toward the electrodes after it has been trapped by the three-pillar microstructure, the impedance and the phase change are measured in an operating frequency range of 1 to 100 kHz. The equivalent circuit model is established and two elements that depend on cell location are used to investigate the impedance change of a single HeLa cell.

Effect of Cell Position on Impedance Measurement in Microfluidic Channel with Planar Microelectrodes and a Three-Pillar Structure

Impedance analysis of single cells offers the possibility of obtaining accurate, reliable, and in-depth information about their pathological condition. In this work, we present the physical capture of a single cell using a microfluidic device with a three-pillar microstructure, impedance measurement using a set of planar microelectrodes, and the derivation of an electrical model that fits the experimental results. The relationship between impedance characteristics and the location of a single HeLa cell (human cervical epithelioid carcinoma) is investigated by impedance spectroscopy. When a single cell fell toward the electrodes after it has been trapped by the three-pillar microstructure, the impedance and the phase change are measured in an operating frequency range of 1 to 100 kHz. The equivalent circuit model is established and two elements that depend on cell location are used to investigate the impedance change of a single HeLa cell.

Synthesis and antitumor activity of lapathoside D and its analogs

Phenylpropanoid sucrose esters are important class of plant-derived natural products and have greater potential to be leads for new drugs because of their structural diversity and broad-array of pharmacological and biological activities. Regio- and chemo-selective acylation of 2,1′:4,6-O-di-isopropylidene sucrose 4 with cinnamoyl chloride 5 and p-acetoxycinnamoyl chloride 6 afforded mono-, di-, tri- and tetra- variant PSEs in moderate yields. The first total synthesis of di-substituted PSE, lapathoside D 1′ has been achieved successfully in short and simple synthetic steps from sucrose 3 as an inexpensive starting material. Lapathoside D 1 and a set of selected synthesized PSEs were tested for in vitro cytotoxicity against human cervical epithelioid carcinoma (HeLa) cell lines. Most of the compounds exhibited significant antitumor activity with their IC50 values ranging from 0.05 to 7.63 μM. The primary screening results indicated that PSEs might be valuable source for new potent anticancer drug candidates.

The elicited two-stage submerged cultivation of Antrodia cinnamomea for enhancing triterpenoids production and antitumor activity

A two-stage submerged fermentation with elicitation was used to increase triterpenoids production of Antrodia cinnamomea in an airlift bioreactor with dual net draft tube. The dual net draft tube bioreactor had higher kLa value (7.3h−1) than the solid tube bioreactor (5.5h−1). The fungus was cultured at 25°C for 12days, then elicited with chemicals and physical factors. It was found that comparing to calcium chloride, chitosan was a more potent chemical elicitor. At dosage level of 100mg/L, it not only resulted in more biomass production but also yielded higher crude triterpenoids production. The triterpenoids production could be significantly enhanced by means of the oxygen limitation and temperature fluctuation strategies. The maximum triterpenoids production could be achieved by using static culture (oxygen limitation) with temperature fluctuation between 25°C (for 10h) and 10°C (for 14h). The in vitro anticancer activity assay indicated that the crude triterpenoids produced by A. cinnamomea using the developed elicited two-stage cultivation protocol effectively inhibited proliferation of human cervical epithelioid carcinoma HeLa cells in a dosage dependent manner. The IC50 of the crude triterpenoids from the mycelium of A. cinnamomea after 21days cultivation for HeLa cells was 25μg/mL.