Human Cancer HeLa Cells Research Articles

Steroidal esters from Ferula sinkiangensis

Two new steroidal esters with an unusual framework, Sinkiangenorin A and B, a new organic acid glycoside, Sinkiangenorin C, and four known lignin compounds were isolated from the seeds of Ferula sinkiangensis. The structures of these compounds were established by spectroscopic analysis and single-crystal X-ray diffraction. All of the isolated compounds were tested against Hela, K562 and AGS human cancer cell lines. Sinkiangenorin C showed cytotoxic activity against AGS cells with an IC50 of 36.9μM.

Cytotoxic cucurbitane triterpenoids isolated from the rhizomes of Hemsleya amabilis

Two new cucurbitane triterpenoids, 7β-hydroxycucurbitacin F-25-O-acetate (1) and 2β,3β,20(S),26,27-pentahydroxy-16α,23(S)-epoxycucurbita-5,24-dien-11-one (2) along with eleven known cucurbitane triterpenoids (3–13, resp.) were isolated from the rhizomes of Hemsleya amabilis Diels. The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of the isolated cucurbitane triterpenoids were evaluated against the HeLa human cancer cell lines. Hemslecin A (5), the main ingredient of H. amabilis, exhibited the significant cytotoxicity with IC50 value of 0.389μM.

In vitro and in vivo antischistosomal activity of ferroquine derivatives.

BackgroundSchistosomiasis is a neglected tropical disease and drug-repurposing is a useful strategy to fill its exhausted drug development pipeline. The ferrocenyl analogue of chloroquine, ferroquine, is an antimalarial in late-stage drug development. The aim of the present work was to study the antischistosomal activity of ferroquine against Schistosoma mansoni adult worms and newly transformed schistosomula (NTS) in vitro and in vivo. Hydroxyl-ferroquine and ruthenoquine were included to study the potential role of reactive oxygen species in the antischistosomal activity. Chloroquine and mefloquine, the later described for its antischistosomal properties, served as comparators.FindingsAll metal complexes were shown to be moderately cytotoxic on human cervix HeLa cancer cells and human fetal lung fibroblasts MRC-5. 72 hours post-incubation NTS exposed to 33.3 µM ruthenoquine had died, while ferroquine and hydroxyl-ferroquine treated worms were strongly affected. No activity was observed treating NTS with chloroquine at 33.3 µM. Incubation of adult S. mansoni with 33.3 µM of the organometallic derivatives were highly affected in viability but were still alive 72 hours post-incubation. Mefloquine showed the highest activity against NTS and adult S. mansoni. Low total worm burden reductions of 0-36% were observed following oral administration of 200–800 mg/kg of the ferroquine derivatives to S. mansoni-infected mice.ConclusionsThe organometallic compounds evaluated in this study revealed moderate in vitro activity against both larval and adult stages of S. mansoni but low in vivo activity. No correlation can be drawn between the antimalarial and antischistosomal activity of chloroquine analogues and oxidative shock does not seem to play a role in the activity of these compounds against S. mansoni.

Effects of Depsidones from Hypogymnia physodes on HeLa Cell Viability and Growth

The anti-proliferative activitiy of Hypogymnia physodes methanol extracts (ME) and its main constituents, physodalic acid (P1), physodic acid (P2), and 3-hydroxy physodic acid (P3), was tested on human cancer HeLa cell lines. Three lichen depsidones, P1, P2 and P3, were isolated from H. physodes ME using column chromatography and their structures were determined by UV, ESI TOF MS, 1H and 13C NMR. The content of P1, P2 and P3 in ME was determined using reversed-phase highperformance liquid chromatography with photodiode array detection. P1–3 represented even 70 % of the studied extract. The HeLa cells were incubated during 24 and 72 h in the presence of ME and depsidones P1, P2 and P3, at concentrations of 10–1000 μg/ml. Compounds P2 and P3 showed higher activity than compound P1. Half maximal inhibitory concentrations (IC50, μg/ml) of P1, P2, P3 and ME for 24-h incubation were 964, 171, 97 and 254 μg/ml, respectively, while for 72-h incubation they were 283, 66, 63 and 68 μg/ml. As far as we know, this is the first report on the effect of H. physodes ME and their depsidones on HeLa cells.

Fabrication and evaluation of the novel reduction-sensitive starch nanoparticles for controlled drug release

A novel type of reduction-sensitive starch nanoparticles was prepared via the reversed-phase microemulsion method by using crosslinker, N,N-bisacryloylcystamine (BAC) with the disulfide linkages, which was specifically cleaved by dithiothreitol (DTT). Starch nanoparticles had a spherical morphology with a small size of 40nm in the optimal condition. The influences of process parameters (starch amount, surfactant amount and oil/water (O/W) ratio) on the size of starch nanoparticles were studied by dynamic light scattering (DLS). BAC crosslinked starch nanoparticles were degraded into oligomers with the reducing agent of DTT due to the cleavage of the disulfide linkages. A model drug 5-aminosalicylic acid (5-ASA) could be loaded efficiently into starch nanoparticles and the in vitro drug release behaviors were also studied. The results suggested that the disulfide crosslinked starch nanoparticles exhibited an accelerated drug release behavior in the presence of DTT. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that BAC crosslinked starch nanoparticles had a good biocompatibility when cocultured with human HeLa cancer cells. Hence, with excellent biocompatibility and biodegradability, and rapid drug release in response to DTT, BAC crosslinked starch nanoparticles showed a great potential as a biomaterial carrier for the application of drug controlled release. In contrast to BAC crosslinked starch nanoparticles, N,N-methylenebisacrylamine (MBA) crosslinked starch nanoparticles were prepared as the control without the disulfide linkages.

Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells.

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer.

A new aromatic amine from fungus Pestalotiopsis vaccinii

A new aromatic amine named pestalamine A (1), as well as a known diketopiperazine (2) and four known phenol or aromatic amine derivatives (3–6) were isolated from mangrove-derived endophytic fungus Pestalotiopsis vaccinii. The structure of pestalamine A (1) was determined by spectroscopic methods, especially 2D NMR analyses. Pestalamine A (1) showed moderate cytotoxicities against MCF-7, HeLa, and HepG2 human cancer cell lines with IC50 values of 40.3, 22.0, and 32.8μM, respectively.

Synthesis and Anticancer Activity of 5-(1,2-Diselenolan-3-Yl)pentanoic Acid and its Derivatives

A green and high-yielding synthetic route for the preparation of 5-(1,2-diselenolan-3-yl)pentanoic acid (SeA) was reported. Some SeA derivatives, N′-substituted benzylidene-5-(1,2-diselenolan-3-yl)pentanehydrazide, were prepared, and they were screened for their anticancer activity against human breast MCF-7, leukemia HL-60, cervixuterus Hela, and placental villus Bewo cancer cell lines. The minimum inhibitory concentrations (MICs) of the synthetic compounds showed moderate anticancer activity at low concentrations (0.5–5 μg/mL).

Evaluation of Chitosan-Tripolyphosphate Nanoparticles as a p-shRNA Delivery Vector: Formulation, Optimization and Cellular Uptake Study

Polysaccharides (especially chitosan) have recently attracted much attention as gene therapy delivery vehicles for their unique properties such as biocompatibility, biodegradability, low toxicity, and controlled release. Nanoparticles have strong potential as a carrier of plasmid short hairpin RNA (p-shRNA). This study aimed to find the optimum conditions for obtaining Chitosan/triphosphate (TPP)/p-shRNA nanoparticles by the ionic gelation method, and investigating the cellular uptake of the optimized nanoparticles. After applying the central composite design of response surface methodology (RSM), the optimum conditions for preparation of nanoparticles with small size and high loading efficiency were: chitosan/TPP ratio = 10, pH = 5.5 and N/P ratio = 11. The resulting nanoparticles had an average size of 172.8 ± 7 nm and loading efficiency of 71.5 ± 5%. SEM images showed spherical and smooth nanoparticles. The nanoparticles complexed with p-shRNA and may protect it against nuclease digestion. Cytotoxicity studies with HeLa and PC3 human cancer cells demonstrated that chitosan/TPP nanoparticles had low toxicity. Cellular uptake studies using HeLa cells showed that the nanoparticles entered the cells (cellular uptake) and delivered DNA, probably due to their favorable Zeta potential (approximately +28 mV) and small size.

Biological Effects of the Aqueous Extract of Bridelia grandis Stem Bark on Normal and Neoplastic Human Cells: An In Vitro Preliminary Evaluation

The aim of the work is to investigate the effects of Bridelia grandis (Pierre ex Hutch) stem bark water extract on human HeLa cancer cells and normal monocytes treated in vitro, evaluating the morphological modifications with light and electron microscopy. The phytocomplex obtained from B. grandis caused a significant decrease in the mitotic index of both HeLa cancer cells and normal monocytes. In addition, a reduction of the typical aneuploid-polyploid pattern has been observed in HeLa cells after treatment. Various alterations at fine structural level, both in neoplastic (HeLa cells) and normal (monocytes) cells have been observed. In particular, electron-dense cells containing condensed mitochondria, autophagic vacuoles and dense spherical cytoplasmic inclusions have been observed. The results show that B. grandis water extracts have an antiproliferative effect on human cells, with a different effect on neoplastic and normal cells. The antiproliferative effect is accompanied by the appearance of various subcellular alterations. The morphological alterations observed are likely to represent the condition of 'dark cell' as a possible preliminary phase towards the autophagic and/or apoptotic cell death.

Triterpene saponins from Tabellae Clinopodii

Three new triterpene saponins, named Clinoposaponin A, Clinoposaponin B, and Clinoposaponin C along with three known triterpene saponins were isolated from the Tabellae Clinopodii. The structures of these compounds were elucidated by means of various spectroscopic analyses. All of the isolated compounds were tested against Hela, HCT-8, AGS, and MCF-7 human cancer cell lines and showed moderate cytotoxic activities with IC50 values between 4.1 and 19.7μM.

Construction of pcDNA 3.1(+)-HRE-Egr-1-Dbait and Its Radiosensitization Effect on Human Cervical Cancer HeLa Cells in Hypoxia Response

Objective To construct recombined eukaryotic expressional vector pcDNA 3.1(+ )-HRE-Egr- 1-Dbait by hypoxia and radiation dual-induced promoter and to observe its radiosensitivity effect on HeLa cells in hypoxia response.Methods Egr-1 promoter elements were amplificated from C57BL/6 nude mice by PCR,Dbait oligonucleotide and HRE enhancer elements were gained by chemical synthesis.The recombined plasmid pcDNA 3.1(+ )-HRE-Egr-l-Dbait was constructed by gene reconstruction.pcDNA 3.1(+ )-HRE-Egr-l-Dbait was transfected into HeLa cells.Colony Formation Assay was used to the detect the radiosensitivity effect transfectants.Results The recombinant plasmids pcDNA 3.1(+ )-HRE-Egr -1-Dbait was constructed and identified by enzyme digestion and sequencing.The D_0,Dq,SF2,α/βvalue of HeLa cells in normal oxygen were 1.98,0.93,0.52,11.12,respectively.The D_0,Dq,SF2 value in hypoxia were 1.74,1.46,0.43,15.82.OER value was 0.88.Conclusion We successfully constructed the combined eukaryotic expressional plasmid vector pcDNA3.1(+ )-HRE-Egr-l-Dbait characterized by radiation and hypoxia dual-induced promoter.And this expression vector could significantly increase the radiosensitivity of human cervical cancer HeLa cells in hypoxic response.

Antiproliferative Activities on Renal, Prostate and Melanoma Cancer Cell Lines of Sarcopoterium spinosum Aerial Parts and its Major Constituent Tormentic Acid

The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. Sarcopoterium spinosum (L.) Spach is mentioned in ethnobotanical surveys as a medicinal plant used for the treatment of cancer. The aim of this study is to investigate and to compare the aerial parts of S. spinosum collected in Italy and Lebanon for their chemical composition and their antiproliferative activity against ACHN, C32, A375, MCF-7, LNCaP and HeLa human cancer cell lines using SRB assay. The main constituent tormentic acid was isolated by MPLC and characterized by spectroscopic techniques (NMR, MS). Non polar compounds were analyzed by GC and GC-MS. S. spinosum showed an interesting antiproliferative activity against ACHN and C32 cell lines with IC(50) values of 2.4 and 2.7 μg/ml for S. spinosum from Italy and Lebanon, respectively. Remarkable results were obtained also against A375 and LNCaP cell lines. The cytotoxicity against ACHN cell line could be partially attributed to tormentic acid that demonstrated a higher cytotoxicity than the positive control vinblastine. Close association between the radical scavenging activity (evaluated by DPPH and ABTS assay) and cytotoxicity was also demonstrated. This investigation demonstrated the potential cytotoxic activity of S. spinosum taking into account also that none of the tested extracts, fractions and isolated compound affected the proliferation of normal cell line 142BR. Tormentic acid, the major constituent isolated from S. spinosum, play an important role in the cytotoxicity exhibited by the extract.

Chrysin overcomes TRAIL resistance of cancer cells through Mcl-1 downregulation by inhibiting STAT3 phosphorylation

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various types of cancer cells without harming normal cells, but TRAIL resistance has been frequently observed in cancer cells. Propolis (bee glue) is a material collected from various plants by honeybees and is a rich source of bioactive compounds, including the natural flavonoid chrysin, which possesses multiple anticancer effects. We investigated the mechanism underlying the TRAIL sensitization effect of chrysin, which is a major constituent of Thai propolis, in human lung and cervical cancer cell lines. Propolis extract and chrysin sensitizes A549 and HeLa human cancer cell lines to TRAIL-induced apoptosis. The TRAIL sensitization effect of chrysin is not mediated by inhibition of TRAIL-induced NF-κB activation or by glutathione depletion. Immunoblot analysis using a panel of anti-apoptotic proteins revealed that chrysin selectively decreases the levels of Mcl-1 protein, by downregulating Mcl-1 gene expression as determined by qRT-PCR. The contribution of Mcl-1 in TRAIL resistance was confirmed by si-Mcl-1 knockdown. Among signaling pathways that regulate Mcl-1 gene expression, only constitutive STAT3 phosphorylation was suppressed by chrysin. The proposed action of chrysin in TRAIL sensitization by inhibiting STAT3 and downregulating Mcl-1 was supported by using a STAT3‑specific inhibitor, cucurbitacin-I, which decreased Mcl-1 levels and enhanced TRAIL-induced cell death, similar to that observed with chrysin treatment. In conclusion, we show the potential of chrysin in overcoming TRAIL resistance of cancer cells and elucidate its mechanism of action.

Novel quinolone substituted thiazolidin-4-ones as anti-inflammatory, anticancer agents: Design, synthesis and biological screening

Nuclear factor-kappaB (NF-κB) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs suppressing or inhibiting NF-κB may possess both anti-inflammatory and anticancer properties. A library of quinolone substituted thiazolidin-4-ones was docked into the active site of NF-κB and the top-ranked 31 compounds were synthesized and evaluated for anti-inflammatory and anticancer activity. The best-ranked compound 6b showed highest anti-inflammatory activity in carrageenan-induced paw edema model. In vitro anticancer studies revealed 1a and 16a as most active compounds against BT-549, HeLa, COLO-205 and ACHN human cancer cell lines. Compounds 1a and 16a exhibited NF-κB dependent anticancer properties and apoptosis mediated cell death. In vivo Ehrlich ascites carcinoma study further confirmed the antitumor activity of 1a and 16a.

Synthesis and antiproliferative activity evaluation of imidazole-based indeno[1,2-b]quinoline-9,11-dione derivatives

A series of new imidazole substituted indeno[1,2-b]quinoline-9,11-dione derivatives were synthesized and evaluated for their antiproliferative effects on HeLa, LS180, MCF-7 and Jurkat human cancer cell lines. Antiproliferative effects were evaluated using MTT assay. Prepared compounds exhibited weak to good antiproliferative activity in evaluated cell lines. Prepared compounds were more potent in Jurkat cell line when compared to LS180, HeLa and MCF-7 cell lines. Compounds 29 (IC16 = 0.7 μM) and 31 (IC16 = 1.7 μM) and 33 (IC16 = 1.7 μM) were found to be the most potent molecules on Jurkat cell lines. Moreover; it was found that some of the tested compounds bearing imidazole-2-yl moiety on the C11-position of dihydropyridine ring exhibited superior antiproliferative activity in comparison to cis-platin especially in Jurkat cell line (compounds 29, 31, and 33). It seemed that the introduction of electron-withdrawing groups on the imidazole ring enhanced the antiproliferative potential of these compounds (compounds 27, 29 and 31). The results of this study proposed that some of the imidazole substituted indeno[1,2-b]quinoline-9,11-dione compounds may act as efficient anticancer agents in vitro, emphasizing their potential role as a source for rational design of potent antiproliferative agents.

Syntheses, DNA Binding and Anticancer Profiles of L-Glutamic Acid Ligand and its Copper(II) and Ruthenium(III) Complexes

A new multidentate ligand (L) has been synthesized by the controlled condensation of L-glutamic acid with formaldehyde and ethylenediamine. Cu(II) and Ru(III) metal ion complexes of the synthesized ligand have also been prepared. The ligand and the metal complexes were purified by chromatography and characterized by spectroscopy and other techniques. Molar conductance measurements suggested ionic nature of the complexes. The ligand and the complexes are soluble in water with quite good stabilities; essential requirements for effective anticancer drugs. DNA binding constants (Kbs) for copper and ruthenium complexes were 1.8 x 103 and 2.6 x 103 M-1 while their Ksv values were 7.9 x 103, and 7.3 x 103; revealing strong binding of these complexes with DNA. Hemolytic assays of the reported compounds indicated their significantly less toxicity to RBCs than the standard anticancer drug letrazole. Anticancer profiles of all the compounds were determined on HepG2, HT-29, MDA-MB-231 and HeLa human cancer cell lines. All the compounds have quite good activities on HeLa cell lines but the best results were of CuL on HepG2, HT-29 and MDA-MB-231 cell lines.

Synthesis, cytotoxicity, and molecular properties prediction of novel 1,3-diarylpyrazole derivatives

A novel combinatorial library of ester and amide derivatives of 1,3-diarylpyrazoles was designed and synthesized. Anticancer activities of these compounds were assessed against MCF7, MDA-MB-231, HeLa, Raji, and HL60 human cancer cells by MTT assay. Out of these, compounds 4c and 5f were found as the most promising anticancer agents with IC50 values of 8.12 and 9.63 μM in Raji cells, respectively. All compounds exhibited suitable drug-like characteristics according to Lipinski’s rule.

Molecular Electronic Tuning of Photosensitizers to Enhance Photodynamic Therapy: Synthetic Dicyanobacteriochlorins as a Case Study

Photophysical, photostability, electrochemical and molecular-orbital characteristics are analyzed for a set of stable dicyanobacteriochlorins that are promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc (NC)2BC-Zn and palladium chelate (NC)2BC-Pd. The order of PDT activity against HeLa human cancer cells in vitro is (NC)2BC-Pd > (NC)2BC > (NC)2BC-Zn ≈ BC. The near-infrared absorption feature of each dicyanobacteriochlorin is bathochromically shifted 35-50 nm (748-763 nm) from that for BC (713 nm). Intersystem crossing to the PDT-active triplet excited state is essentially quantitative for (NC)2BC-Pd. Phosphorescence from (NC)2BC-Pd occurs at 1122 nm (1.1 eV). This value and the measured ground-state redox potentials fix the triplet excited-state redox properties, which underpin PDT activity via Type-1 (electron transfer) pathways. A perhaps counterintuitive (but readily explicable) result is that of the three dicyanobacteriochlorins, the photosensitizer with the shortest triplet lifetime (7 μs), (NC)2BC-Pd has the highest activity. Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins studied recently are investigated and discussed in terms of four phenomena: aggregation, reduction, oxidation and chemical reaction. Collectively, the results and analysis provide fundamental insights concerning the molecular design of PDT agents.

New Nervogenic Acid Derivatives from Liparis nervosa

Ten new nervogenic acid derivatives (1-4, 6-11) and one known compound (5) have been isolated from Liparis nervosa. Their structures were determined using extensive spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 3, 4, 9, 10, and 11 were evaluated for their cytotoxicity against A549, H460, Hela, MCF-7, Caco2, and HepG2 human cancer cell lines.