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Sample records for test cytotoxic effects

  1. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

    Directory of Open Access Journals (Sweden)

    Carolina Ribeiro E Silva

    Full Text Available Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenylprop-2-enoyl]phenyl} benzenesulfonamide (CPN were assessed using the Salmonella typhimurium reverse mutation test (Ames test and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05. The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p 0.05. Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

  2. Evaluation of cytotoxic effects of six self-etching adhesives with direct and indirect contact tests.

    Science.gov (United States)

    Kusdemir, Mahmut; Gunal, Solen; Ozer, Fusun; Imazato, Satoshi; Izutani, Naomi; Ebisu, Shigeyuki; Blatz, Markus B

    2011-01-01

    This study evaluated the cytotoxicity of self-etching primers/adhesives by direct contact and dentin barrier tests. The three two-step self-etching systems Clearfil SE Bond (CSE), Clearfil Protect Bond (CPB), Prime&Bond NT/NRC (PB) and one-step self-etching systems Reactmer Bond (RB), Clearfil Tri-S Bond (CTS), and Adper Prompt L-Pop (AP) were examined. In direct contact tests, L929 cells were cultured in the presence of diluted solutions (50, 20, 10, and 1%) of primer/conditioner of adhesive systems. For dentin barrier tests, each system was applied onto 0.5 or 1.5 mm thick human dentin assembled in a simple pulp chamber device and incubated for 24 h at 37°C to make the diffusive components contact the L929 cells placed at the bottom of the chamber. The cytotoxic effects were assessed by MTT assay. Cell culture without application of any primers/adhesives served as the control for both tests. One-way ANOVA and Tukey HSD tests were used for statistical analyses. The direct contact tests demonstrated that CSE and CPB were less toxic than the other materials at all dilutions. In the dentin barrier tests, toxic effects of materials were reduced with an increase in thickness of intervening dentin. CSE and CPB showed less cytotoxicity than the other adhesives (psystems. Two-step self-etching systems with HEMA-based primers were more biocompatible than other self-etching adhesives.

  3. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

    Science.gov (United States)

    Silva, Carolina Ribeiro E; Borges, Flávio Fernandes Veloso; Bernardes, Aline; Perez, Caridad Noda; Silva, Daniela de Melo E; Chen-Chen, Lee

    2015-01-01

    Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p tested at 24 h (p 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

  4. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test.

    Science.gov (United States)

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin-a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P Allium. Pretreatment of Allium sativum with quercetin significantly (P Allium sativum that resides, at least in part, on its antioxidant effects.

  5. CYTOTOXICITY TESTING OF WOUND DRESSINGS USING METHYLCELLULOSE CELL-CULTURE

    NARCIS (Netherlands)

    VANLUYN, MJA; VANWACHEM, PB; NIEUWENHUIS, P; JONKMAN, MF

    1992-01-01

    Wound dressings may induce cytotoxic effects. In this study, we check several, mostly commercially available, wound dressings for cytotoxicity. We used our previously described, newly developed and highly sensitive 7 d methylcellulose cell culture with fibroblasts as the test system. Cytotoxicity is

  6. Determination of mutagenic and cytotoxic effects of Limonium globuliferum aqueous extracts by Allium, Ames, and MTT tests

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    Yasin Eren

    Full Text Available Mutagenic and cytotoxic effects of roots, stems and leaves of Limonium globuliferum Kuntze, Plumbaginaceae, aqueous extracts were studied by Allium, Ames, and MTT tests. These are plant, bacterial and mammalian cell assays, respectively. The Allium test analyses showed that aqueous extracts of this species have dose-dependent toxicity and induce chromosomal anomalies based on defects in the spindle fibers. EC50 values of root stem and leaf aqueous extracts were 32.5, 50, and 50 g/l, respectively. It was observed that there was an inverse correlation between root growth and extract concentration. The lowest mitotic index value (22.72 % was found in L. globuliferum root extract. As a result of the chromosome aberrations test, sticky chromosomes, anaphase bridges, laggard chromosomes, and anaphase-telophase disorders were highly detected especially in high concentration of the extract. In the Ames test, mutagenic effects were determined at all concentrations of stem and leaf aqueous extracts and only two concentrations of root extracts of L. globuliferum. Most of the extracts induced cytotoxic effects by the MTT test based on mitochondrial activity. Nevertheless, some of the extracts induced t cell proliferation.

  7. Cytotoxicity effects of alkoxy

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    Wan M. Khairul

    2017-05-01

    Full Text Available In this study, the effort was to design and synthesize five new members of alkoxy substituted thiourea derivatives (3a–3e featuring general formula of A-ArC(ONHC(SNHAr-D in which A represents the methoxy group and D as –OCnH2n+1 (alkoxyl group, where n = 6,7,8,9, and 10 have been successfully designed, prepared, characterized, and evaluated for anti-amoebic activities. They were spectroscopically characterized by 1H and 13C Nuclear Magnetic Resonance (NMR, Fourier Transform Infrared (FT-IR spectroscopy, and Ultraviolet–visible (UV–vis spectroscopy analysis. In turn, they were used to investigate the cytotoxicity effect on Acanthamoeba sp. at their IC50 values and membrane permeability. Compounds 3a and 3b revealed to have good activity towards Acanthamoeba sp. compared to other compounds of 3c, 3d, and 3e. The observation under fluorescence microscopy by AOPI (Acridine-orange/Propidium iodide staining indicated that treated amoeba cells by 3a–3e show loss of their membrane permeability.

  8. Testing the genotoxicity, cytotoxicity, and oxidative stress of cadmium and nickel and their additive effect in male mice.

    Science.gov (United States)

    El-Habit, Ola H; Abdel Moneim, Ahmed E

    2014-06-01

    The present study was aimed to investigate the ability of cadmium (Cd) and nickel (Ni) to induce genotoxicity, cytotoxicity, and oxidative stress in bone marrow cells of male mice. Aneuploidy and chromosomal aberrations (CA) showed that Cd is a stronger mutagen than Ni. Cd and Ni increased significantly the incidences of micronucleated polychromatic erythrocytes (PCEs). Also, the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) suggests that treatment with higher doses of the two metals increased the cytotoxicity. Numerical chromosomal aberrations increased hypoploidy with the treatment which reached two to three times of the frequency of hyperploidy. The results showed that both Cd and Ni are aneugenic that act on kinetochores and cause malsegregation of chromosomes as well as being clastogenic. Both Cd and Ni increased single-break aberrations and also Cd and Ni were found to induce significant DNA damage in mouse bone marrow cells as assessed by the comet assay. In addition to the cytotoxicity results, biochemical analysis in bone marrow revealed a dose-dependent increase of oxidative stress markers. According to the results obtained, genotoxicity and cytotoxicity effects of cadmium and nickel in vivo are dose-dependent and are associated with oxidative stress and their combined effect is less than their expected additive effect, and it could be concluded that there are no synergistic effects resulting from the combined application of both metals.

  9. Cytotoxicity testing of wound dressings using methylcellulose cell culture.

    Science.gov (United States)

    van Luyn, M J; van Wachem, P B; Nieuwenhuis, P; Jonkman, M F

    1992-01-01

    Wound dressings may induce cytotoxic effects. In this study, we check several, mostly commercially available, wound dressings for cytotoxicity. We used our previously described, newly developed and highly sensitive 7 d methylcellulose cell culture with fibroblasts as the test system. Cytotoxicity is assessed by monitoring cell growth inhibition, supported by cell morphological evaluation using light and transmission electron microscopy. We tested conventional wound dressings, polyurethane-based films, composites, hydrocolloids and a collagen-based dressing. It was shown that only 5 out of 16 wound dressings did not induce cytotoxic effects. All 5 hydrocolloids were found to inhibit cell growth (greater than 70%), while cells had strongly deviant morphologies. The remaining wound dressings showed medium cytotoxic effects, with cell growth inhibition, which varied from low (+/- 15%), medium-low (+/- 25%) to medium-high (+/- 50%). Measurable cytotoxic effects of dressings detected in vitro are likely to interfere with wound healing when applied in vivo. The results are discussed in view of the clinical uses with contaminated wounds, impaired epithelialization or hypergranulation.

  10. [In vitro cytotoxicity test of medical ultrasonic couplant].

    Science.gov (United States)

    Gao, Jingxian; Wang, Shasha; Jin, Meng; Yan, Xiaoli

    2013-05-01

    The cytotoxicity of medical ultrasonic couplant was tested by MTT assay and agar overlay test. By MTT assay, when the inoculum density was high, the cytotoxicity level was low, or vice versa. The cytotoxicity grade tested by agar overlay was not accord to MTT assay's too. MTT assay is suitable to test the cytotoxicity of medical ultrasonic couplant because it is quantitative and more sensitive, however, the experimental condition and the preparative method of extraction should be determined.

  11. Improved cytotoxicity testing of magnesium materials

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Janine, E-mail: janine.fischer@hzg.de [Helmholtz-Zentrum Geesthacht, Institute of Materials Research, Department for Structural Research on Macromolecules, Max-Planck Str. 1, D - 21502 Geesthacht (Germany); Proefrock, Daniel [Helmholtz-Zentrum Geesthacht, Institute for Coastal Research, Department for Marine Bioanalytical Chemistry, Max-Planck Str. 1, D - 21502 Geesthacht (Germany); Hort, Norbert [Helmholtz-Zentrum Geesthacht, Institute of Materials Research, Department for Magnesium Processing, Max-Planck Str. 1, D - 21502 Geesthacht (Germany); Willumeit, Regine; Feyerabend, Frank [Helmholtz-Zentrum Geesthacht, Institute of Materials Research, Department for Structural Research on Macromolecules, Max-Planck Str. 1, D - 21502 Geesthacht (Germany)

    2011-06-25

    Metallic magnesium (Mg) and its alloys are highly suitable for medical applications as biocompatible and biodegradable implant materials. Magnesium has mechanical properties similar to bone, stimulates bone regeneration, is an essential non-toxic element for the human body and degrades completely within the body environment. In consequence, magnesium is a promising candidate as implant material for orthopaedic applications. Protocols using the guideline of current ISO standards should be carefully evaluated when applying them for the characterization of the cytotoxic potential of degradable magnesium materials. For as-cast material we recommend using 10 times more extraction medium than recommended by the ISO standards to obtain reasonable results for reliable cytotoxicity rankings of degradable materials in vitro. In addition primary isolated human osteoblasts or mesenchymal stem cells should be used to test magnesium materials.

  12. Comparison of cytotoxic and genotoxic effects of plutonium-239 alpha particles and mobile phone GSM 900 radiation in the Allium cepa test.

    Science.gov (United States)

    Pesnya, Dmitry S; Romanovsky, Anton V

    2013-01-20

    The goal of this study was to compare the cytotoxic and genotoxic effects of plutonium-239 alpha particles and GSM 900 modulated mobile phone (model Sony Ericsson K550i) radiation in the Allium cepa test. Three groups of bulbs were exposed to mobile phone radiation during 0 (sham), 3 and 9h. A positive control group was treated during 20min with plutonium-239 alpha-radiation. Mitotic abnormalities, chromosome aberrations, micronuclei and mitotic index were analyzed. Exposure to alpha-radiation from plutonium-239 and exposure to modulated radiation from mobile phone during 3 and 9h significantly increased the mitotic index. GSM 900 mobile phone radiation as well as alpha-radiation from plutonium-239 induced both clastogenic and aneugenic effects. However, the aneugenic activity of mobile phone radiation was more pronounced. After 9h of exposure to mobile phone radiation, polyploid cells, three-groups metaphases, amitoses and some unspecified abnormalities were detected, which were not registered in the other experimental groups. Importantly, GSM 900 mobile phone radiation increased the mitotic index, the frequency of mitotic and chromosome abnormalities, and the micronucleus frequency in a time-dependent manner. Due to its sensitivity, the A. cepa test can be recommended as a useful cytogenetic assay to assess cytotoxic and genotoxic effects of radiofrequency electromagnetic fields. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Long-term cytotoxic effects of contemporary root canal sealers

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    Emmanuel Joao Nogueira Leal da SILVA

    2013-03-01

    Full Text Available Objectives The aim of the present study was to investigate the effects of root canal sealers on the cytotoxicity of 3T3 fibroblasts during a period of 5 weeks. Material and Methods Fibroblasts (3T3, 1×105 cells per well were incubated with elutes of fresh specimens from eight root canal sealers (AH Plus, Epiphany, Endomethasone N, EndoREZ, MTA Fillapex, Pulp Canal Sealer EWT, RoekoSeal and Sealapex and with elutes of the same specimens for 5 succeeding weeks after immersing in simulated body fluid. The cytotoxicity of all root canal sealers was determined using the MTT assay. Data were analyzed using ANOVA and Tukey's test. Results RoekoSeal was the only sealer that did not show any cytotoxic effects (p<0.05. All the other tested sealers exhibited severe toxicity initially (week 0. MTA Fillapex remained moderately cytotoxic after the end of experimental period. Toxicity of the other tested sealers decreased gradually over time. The evaluated root canal sealers presented varying degrees of cytotoxicity, mainly in fresh mode. Conclusions RoekoSeal had no cytotoxic effect both freshly mixed and in the other tested time points. MTA Fillapex was associated with significantly less cell viability when compared to the other tested root canal sealers.

  14. Assessing the cytotoxic and mutagenic effects of secondary metabolites produced by several fungal biological control agents with the Ames assay and the VITOTOX(®) test.

    Science.gov (United States)

    Kouvelis, Vassili N; Wang, Chengshu; Skrobek, Anke; Pappas, Katherine M; Typas, Milton A; Butt, Tariq M

    2011-05-18

    The potential genotoxic effects of several pure secondary metabolites produced by fungi used as biological control agents (BCAs) were studied with the Ames Salmonella/microsome mutagenicity assay and the Vitotox test, with and without metabolic activation. A complete set of Salmonella tester strains was used to avoid false negative results. To detect possible mutagenic and/or cytotoxic effects of fungal secondary metabolites due to synergistic action, crude extracts and fungal cell extracts of the BCAs were also examined. Although the sensitivity of the methods varied depending on the metabolite used, clearly no genotoxicity was observed in all cases. The results of the two assays are discussed in the light of being used in a complementary fashion for a convincing risk-assessment evaluation of fungal BCAs and their secondary metabolites. 2011 Elsevier B.V. All rights reserved.

  15. Identification of novel metabolite and its cytotoxic effect on human ...

    African Journals Online (AJOL)

    A novel metabolite of P. polonicum was recently isolated from Cameroonian Zea mays by means of preparative silica gel thin layer chromatographic method. The potential cytotoxic effects of this novel compound was further tested, in vitro, against cultured human mononuclear lymphocyte cells over 18-hr period in ...

  16. Cytotoxic testing for food allergy: evaluation of reproducibility and correlation.

    Science.gov (United States)

    Benson, T E; Arkins, J A

    1976-10-01

    Cytotoxic food tests still present conflicting opinions concerning their validity. Nine atopic patients with or without a history of food allergy were studied along with 5 nonatopic patients. All tests were conducted in a double-blind fashion with 6 determinations for each of 10 food antigens. Reproducibility of the test (5/6 positive or negative) was demonstrated with wheat, milk, yeast, chocolate, and orange. In the nonatopic group, reproducible results were obtained for wheat, egg, yeast, chocolate, and chicken. Clinical correlation with 11 foods in 7 patients was demonstrated. However, there were 46 positive tests without correlation and 2 negative tests with positive histories. Therefore, there appears to be reproducibility of the tests to only 3 foods but no apparent correlation with clinical symptoms. At the present time, cytotoxic tests offer no reliable help in establishing the diagnosis of food allergy.

  17. A mutagenicity and cytotoxicity study of limonium effusum aqueous extracts by Allium, Ames and MTT tests.

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    Eren, Y; Ozata, A; Konuk, M; Akyil, D; Liman, R

    2015-01-01

    Nowadays plants or plant extracts have become very important for alternative medicine. Plants and their extracts have many therapeutical advantages but some of them are potentially toxic, mutagenic, carcinogenic and teratogenic. Root, stem and leafparts of Limonium effusum were used in this study and this species is an endemic species for Turkey. Mutagenic and cytotoxic effects of root, stem and leaf aqueous extracts were observed with Allium, Ames and MTT tests. Allium root growth inhibition test and mitotic index studies showed that aqueous extracts have dose-dependent toxic effects. Chromosome aberration studies indicated that especially sticky chromosome, anaphase-telophase disorder and laggard chromosome anomalies were highly observed. Ames test performed with Limonium effusum root aqueous extracts, showed weak mutagenic effects in Salmonella typhimurium TA98 strain with S9. MTT test based on mitochondrial activity indicated that most of the aqueous extracts have cytotoxic effects. This study aimed to determine the possible mutagenic and cytotoxic effects of L. effusum aqueous extracts by using bacterial, plant and mammalian cells. This research showed that some low concentrations of the L. effusum extracts have inhibited cytotoxic effects but high concentrations have induced cytotoxicity. On the other hand only a weak mutagenic activity was identified by Ames test with TA98 S9(+).

  18. Cytotoxicity testing of aqueous extract of bitter leaf ( Vernonia ...

    African Journals Online (AJOL)

    Cytotoxicity testing of aqueous extract of bitter leaf ( Vernonia amygdalina Del ) and sniper 1000EC (2,3 dichlorovinyl dimethyl phosphate) using the Alium cepa ... 96 hours and EC50 values at 95% confidence interval was determined from a plot of root length against sample concentrations using Microsoft Excel software.

  19. Cytotoxicity of eight cigarette smoke condensates in three test systems: comparisons between assays and condensates.

    Science.gov (United States)

    Richter, Patricia A; Li, Albert P; Polzin, Gregory; Roy, Shambhu K

    2010-12-01

    Cytotoxic properties of tobacco smoke are associated with chronic tobacco-related diseases. The cytotoxicity of tobacco smoke can be tested with short-term predictive assays. In this study, we compare eight mainstream cigarette smoke condensates (CSCs) from commercial and experimental cigarettes in three different cytotoxicity assays with unique and overlapping endpoints. The CSCs demonstrated cytotoxicity in all assays. In the multiple cytotoxicity endpoint (MCE) assay with TK-6 cells, the cigarette varieties that had the highest EC50s for reduced cell growth also showed a positive dose-response relationship for necrotic cells. In the IdMOC multiple cell-type co-culture (MCTCC) system, all CSCs reduced the viability of the cells. Low concentrations of some CSCs had a stimulatory effect in lung microvascular endothelial cells and small airway epithelial cells. In the neutral dye assay (NDA), except for a 100% flue-cured tobacco CSC, there was little consistency between CSCs producing morphological evidence of moderate or greater toxicity and the CSCs with the lowest EC50s in the MCE or MCTCC assays. Overall, cigarettes made with flue-cured tobacco were the most cytotoxic across the assays. When results were expressed on a per-mg of nicotine basis, lower tar cigarettes were the most cytotoxic in primary human respiratory cells. Published by Elsevier Inc.

  20. Cytotoxicity testing of bare CdSe quantum dots and their encapsulated structure

    Science.gov (United States)

    Kumari, Asha; Singh, Ragini Raj

    2017-07-01

    In this work we have synthesized CdSe quantum dots (QDs) and their polymer encapsulated structures by wet chemical method for cytotoxicity testing. These QDs were synthesized by using aqueous solvent to make them hydrophilic because we want to use these for bioimaging purpose. The cytotoxicity is major concern to use these quantum dots in bio application because these are made up of heavy metal ions so to make these QDs nontoxic and to improve their optical properties we encapsulated these QDs by polymers. Thereafter we have studied the cytotoxicity of CdSe QDs and their polymer encapsulated structure.MTT method (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method) was used to study toxicity of QDs toward MDCK epithelial cell line. Effect of encapsulation on optical properties was analyzed by Photoluminescence spectroscopy. QDs encapsulated with polymer possess improved optical properties with greater fluorescence intensity and lesser cytotoxicity as compare to bare CdSe.

  1. Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma

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    Ryuichiro Kimura

    2013-10-01

    Full Text Available In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma.

  2. In vitro cytotoxicity testing of Ubiquicidin 29-41-{sup 99m}Tc

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    Ocampo, Ivette Z.; Okazaki, Kayo; Dias, Luis Alberto Pereira; Higa, Olga Z.; Silva, Fabiana M. da; Vieira, Daniel P., E-mail: dpvieira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Passos, Priscila; Esteves-Pedro, Natalia M., E-mail: fabiana@biosintesis.com.br [Laboratorio Biosintesis Ltda, Sao Paulo, SP (Brazil)

    2015-07-01

    The work carried out cytotoxicity tests using a radiopharmaceutical compound produced at IPEN/CNEN-SP to certify its safety through in vitro cytotoxicity tests. Since 2009, the Brazilian regulatory agency (ANVISA) requires that such tests have to be carried out following good laboratory practices (GLP) and in according to the OECD (Organisation for Economic Co-operation and Development) guidelines in order to certify its safety for medical use. Those guidelines comprises series of technical recommendations performed to assure quality of experiments. The study chose Ubiquicidin 29-41, an antimicrobial peptide used to discriminate bacterial infection foci from inflammatory sites. Amounts of UBI{sub 29-41} were conjugated or not to {sup 99m}Tc and diluted to equivalent concentrations of 10, 100 and 1000% of the maximum dose (or activity) administered in adults. Possible cytotoxic effects were evaluated in comparison to untreated controls as well as positive and negative damage controls. Both full (radioactive) radiopharmaceuticals, as their precursors (only molecules without conjugation to isotopes) showed no significant cytotoxic effect (cytotoxicity ≤ 10%). The study was conducted for the first time in the country comprising preclinical testing of this radiopharmaceutical in accordance with internationally accepted quality parameters, ensuring the safety of its use and enabling inclusion in the pharmaceutical regulatory agenda. (author)

  3. Effect of serum concentration on the cytotoxicity of clay particles.

    Science.gov (United States)

    Lordan, Sinéad; Higginbotham, Clement L

    2012-01-01

    Nanoparticle cytotoxicity testing based on in vitro methods frequently lack consistency. Even the inclusion of the commonly employed growth supplement, FCS (fetal calf serum), generates variable results. Thus, our object was to investigate the effect of FCS concentration on the cytotoxic behaviour of the unmodified nanoclay, Cloisite® Na(+). Human monocytic U937 cells in medium supplemented with 5% FCS, 2.5% FCS or serum-free medium were treated with 1 mg/ml Cloisite Na(+). Cell growth in 2.5% FCS was significantly inhibited by Cloisite Na(+) within 48 h, whereas little effect was seen with a supplement of 5% FCS. Without serum, cell growth was inhibited and Cloisite Na(+) had a detrimental effect on these cells. In media supplemented with FCS, the nanoclays agglomerated together to form large bundles, whereas they were evenly dispersed throughout the medium in the absence of serum. Clay particles, therefore, have cytotoxic properties that may be linked to their dispersion pattern. These adverse effects seem to be masked by 5% FCS. Serum supplementation is an important consideration in the toxicological assessments of nanomaterials on cells, which needs to be addressed in the standardization of in vitro testing methods. © The Author(s) Journal compilation © 2012 Portland Press Limited

  4. Reprint of: Improved cytotoxicity testing of magnesium materials

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Janine, E-mail: janine.fischer@hzg.de [Helmholtz-Zentrum Geesthacht, Institute of Materials Research, Department for Structural Research on Macromolecules, Max-Planck Str. 1, D - 21502 Geesthacht (Germany); Proefrock, Daniel [Helmholtz-Zentrum Geesthacht, Institute for Coastal Research, Department for Marine Bioanalytical Chemistry, Max-Planck Str. 1, D - 21502 Geesthacht (Germany); Hort, Norbert [Helmholtz-Zentrum Geesthacht, Institute of Materials Research, Department for Magnesium Processing, Max-Planck Str. 1, D - 21502 Geesthacht (Germany); Willumeit, Regine; Feyerabend, Frank [Helmholtz-Zentrum Geesthacht, Institute of Materials Research, Department for Structural Research on Macromolecules, Max-Planck Str. 1, D - 21502 Geesthacht (Germany)

    2011-12-15

    Metallic magnesium (Mg) and its alloys are highly suitable for medical applications as biocompatible and biodegradable implant materials. Magnesium has mechanical properties similar to bone, stimulates bone regeneration, is an essential non-toxic element for the human body and degrades completely within the body environment. In consequence, magnesium is a promising candidate as implant material for orthopaedic applications. Protocols using the guideline of current ISO standards should be carefully evaluated when applying them for the characterization of the cytotoxic potential of degradable magnesium materials. For as-cast material we recommend using 10 times more extraction medium than recommended by the ISO standards to obtain reasonable results for reliable cytotoxicity rankings of degradable materials in vitro. In addition primary isolated human osteoblasts or mesenchymal stem cells should be used to test magnesium materials.

  5. Aseptic simulation test for cytotoxic drug production in isolators.

    Science.gov (United States)

    Savry, Amandine; Correard, Florian; Bennis, Youssef; Roubaud, Sophie; Gauthier-Villano, Laurence; Pisano, Pascale; Pourroy, Bertrand

    2014-03-15

    The results of a media-fill test (MFT) study to validate processes for cytotoxic drug preparation inside and outside aseptic compounding isolators are presented. Using an MFT protocol adapted to institution-specific production conditions, the pharmacy team at a hospital in France performed a series of tests to verify the efficacy of decontamination and sterile compounding procedures, as required by French compendial standards, while assessing the performance of its team of 12 isolator operators; all operators were tested on three occasions, producing 10 MFT samples per test for a total of 30 samples per operator. The team also tested alternative compounding systems (i.e., two closed-system transfer devices and a classic spike system) for use during power outages or other emergencies precluding drug preparation within isolators. MFTs were performed using a standard tryptone soy broth-based test kit under worst-case conditions. The hospital's facilities for cytotoxic drug preparation were found to be in conformance with applicable sterility standards. Bacterial growth was not detected in any of the MFT samples produced by isolator operators during the study (total n = 360). In one instance, an MFT sample prepared using a closed-system transfer device was found to be contaminated due to improper cleaning of the medication vial, highlighting the importance of strict adherence to proper decontamination procedures. A hospital's practices for preparation of sterile products according to applicable good manufacturing guidelines, as well as emergency procedures for cytotoxic drug preparation outside isolators, were validated by the results of an MFT study.

  6. Cytotoxic effect of a dentin bonding agent: AdheSE

    Directory of Open Access Journals (Sweden)

    Banava S.

    2007-05-01

    Full Text Available Background and Aim: An important requirement for a dentin bonding agent is biological compatibility. Since dentin bonding agents are placed in cavity preparations with subgingival extensions, with direct contact to gingival and mucosal tissues, tissue response to these materials must be investigated. The aim of this study was to examine the cytotoxicity of AdheSE, a self etching adhesive, on human gingival fibroblasts."nMaterials and Methods: In this experimental in vitro study, primary human gingival fibroblasts were exposed to different dilutions of primer & bond of AdheSE (Vivadent, Liechtenstein. The toxicity of the primer was tested in 30 seconds, 300 seconds and 24 hours. The cytotoxicity of the bond was analyzed in uncured mode after 20 seconds, 5 minutes and 24 hours. In cured mode, tested materials were analyzed after 24 and 48 hours. Cytotoxic effects were evaluated using MTT, cell counting and DNA condensation assays. Data were analyzed by two way repeated measure ANOVA with p<0.05 as the level of significance."nResults: MTT Assay revealed that uncured AdheSE Bond was toxic only in 10-1 dilution and the difference with control group was significant (P<0.05. By increasing the time to 300sec. and 24h, dilutions of 10-2 and 10-4 were the most cytotoxic respectively. Cytotoxicity of uncured primer after 30 sec. and 300 sec. began from 10-2 and after 24h began from 10-2 and reached to 10-1. AdheSE in cured mode showed significant difference with control group in 1:2 (P<0.001,1:4 & 1:6 (P<0.01 dilutions. In cell counting assay only the 1:2 dilution was significantly more toxic than control group. Apoptosis (a morphological and biochemical distinct form of cell death that regulates cell turnover comprised in less than 5% of total death in both cured and uncured adhesives."nConclusions: Based on the results of this study, by increasing the exposure time, smaller amounts of bonding could be cytotoxic. Cytotoxicity was related to material

  7. Cytotoxic effects exerted by Tritrichomonas foetus pseudocysts.

    Science.gov (United States)

    Pereira-Neves, Antonio; Nascimento, Ligia Ferreira; Benchimol, Marlene

    2012-07-01

    The protozoan parasite Tritrichomonas foetus displays a pear-shaped form and a pseudocyst stage. However, little is known about the biology of the pseudocyst. The aim of this work was to assess whether pseudocysts exert cytotoxic effects during their interaction with MDCK cells (an epithelial kidney canine cell line) and compare their behavior to that of the pear-shaped parasites. Pseudocysts and pear-shaped parasites from both cultured and freshly isolated T. foetus were used. Electron microscopy revealed that the epithelial cells exhibited more signs of injury, such as depletion of microvilli, retraction from neighboring cells and swollen mitochondria with loss of electron density in the matrix, when the pseudocysts were used in interaction experiments. In addition, during the co-incubation with MDCK cells, pseudocysts exhibited a more intense amoeboid transformation than that found in pear-shaped parasites. The MTT viability assay demonstrated that the pseudocysts were more cytotoxic when in contact with host cells as compared to the flagellated pear-shaped parasites. The JC-1 viability assay revealed that pseudocysts induced a higher loss of mitochondrial membrane potential compared to pear-shaped parasites. Pseudocysts undergoing a budding process were observed after 2.5h of co-incubation with MDCK cells. Our results suggest that the T. foetus pseudocyst might be a more aggressive form. Copyright © 2011 Elsevier GmbH. All rights reserved.

  8. Antimicrobial and cytotoxic effects of Mexican medicinal plants.

    Science.gov (United States)

    Jacobo-Salcedo, Maria del Rosario; Alonso-Castro, Angel Josabad; Salazar-Olivo, Luis A; Carranza-Alvarez, Candy; González-Espíndola, Luis Angel; Domínguez, Fabiola; Maciel-Torres, Sandra Patricia; García-Lujan, Concepción; González-Martínez, Marisela del Rocio; Gómez-Sánchez, Maricela; Estrada-Castillón, Eduardo; Zapata-Bustos, Rocio; Medellin-Milán, Pedro; García-Carrancá, Alejandro

    2011-12-01

    The antimicrobial effects of the Mexican medicinal plants Guazuma ulmifolia, Justicia spicigera, Opuntia joconostle, O. leucotricha, Parkinsonia aculeata, Phoradendron longifolium, P. serotinum, Psittacanthus calyculatus, Tecoma stans and Teucrium cubense were tested against several human multi-drug resistant pathogens, including three Gram (+) and five Gram (-) bacterial species and three fungal species using the disk-diffusion assay. The cytotoxicity of plant extracts on human cancer cell lines and human normal non-cancerous cells was also evaluated using the MTT assay. Phoradendron longifolium, Teucrium cubense, Opuntia joconostle, Tecoma stans and Guazuma ulmifolia showed potent antimicrobial effects against at least one multidrug-resistant microorganism (inhibition zone > 15 mm). Only Justicia spicigera and Phoradendron serotinum extracts exerted active cytotoxic effects on human breast cancer cells (IC50 < or = 30 microg/mL). The results showed that Guazuma ulmifolia produced potent antimicrobial effects against Candida albicans and Acinetobacter lwoffii, whereas Justicia spicigera and Phoradendron serotinum exerted the highest toxic effects on MCF-7 and HeLa, respectively, which are human cancer cell lines. These three plant species may be important sources of antimicrobial and cytotoxic agents.

  9. Genotoxic and cytotoxic effects of storax in vitro.

    Science.gov (United States)

    Karadeniz, Bulent; Ulker, Zeynep; Alpsoy, Lokman

    2013-03-01

    The aim of this study is to investigate the effects of the storax balsam, which is a kind of sweet gum obtained from the Liquidambar orientalis Mill trees, on cell viability, cytotoxicity and genotoxicity in human lymphocyte in vitro. We studied the genotoxic effects of the extract of storax balsam (SE) using sister chromatid exchange (SCE) test system. Also the cytotoxic and inhibitory effects on cell proliferation of SE were evaluated using lactate dehydrogenase (LDH) assay and cell proliferation (WST-1) assay. The SCE frequency was increased when the cells were treated with 1.6 and 4.0 µg/mL SE concentrations (p < 0.05). Moreover, treatment of the cells with the same concentrations significantly depleted the cell number at 24th and 48th hours and elevated the LDH levels (p < 0.05) at 48th hour. These results suggest that SE can be used as an alternative antibacterial and antipathogenic agent due to its cytotoxic and genotoxic effects.

  10. Antioxidant and Cytotoxic Effects of Moltkia aurea Boiss

    Directory of Open Access Journals (Sweden)

    Iclal Saracoglu

    2012-01-01

    Full Text Available The water extract of M. aurea exhibited strong scavenging effect on 2,2-diphenyl-1-picrylhydrazil ( DPPH, nitric oxide (NO and superoxide (SO radicals. The free radical scavenging effect of the extract was found comparable to that of reference antioxidants, 3-t-butyl-4-hydroxyanizole (BHA and ascorbic acid (AA, vitamin C. Cytotoxic activity of the extract was also investigated against three different cancer cell lines, Hep-2 (human larynx epidermoid carcinoma, RD (human rhabdomyosarcoma, L-20B (transgenic murine L-cells and one non-cancerous cell line (VERO- African green monkey kidney epithelial cell using 3-(4,5- dimethylthiazol-2-yl-2,5-diphenytetrazolium bromide (MTT assayty. While dose dependent cytotoxic activity was observed against cancer cell lines, no cytotoxic effect on VERO cell line was found in the tested expe In addition, phochemical investigations to identify chemical content of the plant were resulted to the isolation of (+-syringaresinol-4′-O- b -glucopyranoside (1, p-hydroxybenzaldehyde (2, quercetin-3-O-rutinoside (Rutine, 3 and isorhamnetin-3-O-rutinoside (4 on the basis of different spectroscopic techniques (UV, IR, 1D and 2D NMR, HR ESI-MS.

  11. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

    Science.gov (United States)

    2011-01-01

    Background Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. Methods The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 μg/mL (crude extract) and 1-10 μg/mL (compound). Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue. In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3 cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. Results Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an α-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an α-methylene carboxylic acid. Cytotoxicity of EPD for normal fibroblasts at all time points IC50 was greater than 10 μg/mL, whereas, for OVCAR3 cells at 48 hours IC50 was 5.3 μg/mL (95% confidence interval 4.3 to 6.5 μg/mL). Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 μg/mL and 5 μg/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects. Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly different, P = 0.13. Conclusions

  12. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

    Directory of Open Access Journals (Sweden)

    van Haard Paul MM

    2011-03-01

    Full Text Available Abstract Background Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. Methods The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 μg/mL (crude extract and 1-10 μg/mL (compound. Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue. In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3 cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. Results Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an α-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an α-methylene carboxylic acid. Cytotoxicity of EPD for normal fibroblasts at all time points IC50 was greater than 10 μg/mL, whereas, for OVCAR3 cells at 48 hours IC50 was 5.3 μg/mL (95% confidence interval 4.3 to 6.5 μg/mL. Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 μg/mL and 5 μg/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects. Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly

  13. Evaluation of Cytotoxicity and Antifertility Effect of Artemisia kopetdaghensis

    OpenAIRE

    Oliaee, Davood; Boroushaki, Mohammad Taher; Oliaee, Naiime; Ghorbani, Ahmad

    2014-01-01

    To date, there is no report on safety of Artemisia Kopetdaghensis. This study aimed to determine the possible undesirable effects of A. Kopetdaghensis on reproduction of female rats. The pregnant rats were treated (i.p.) with vehicle or 200 and 400 mg/kg of A. Kopetdaghensis hydroalcoholic extract from the 2nd to 8th day of pregnancy. Then, number and weight of neonates, duration of pregnancy, and percent of dead fetuses were determined. Also, cytotoxicity of this plant was tested using fibro...

  14. Pharmacodynamic and cytotoxicity effects of Syzygium cordatum {S ...

    African Journals Online (AJOL)

    Purpose: To evaluate the pharmacodynamic effect and cytotoxicity of S. cordatum pulp extract in the ... and may therefore be clinically safe for use at low concentrations as an antidiarrheal agent. Keywords: Syzyhium cordatum, Antibacterial, Antidiarrheal, Antimotility, Cytotoxicity .... penicillin-streptomycin in static flask.

  15. Evaluation Of Potential Cytotoxic Effects Of Herbal Extracts

    Directory of Open Access Journals (Sweden)

    Radovanovic Ana

    2015-12-01

    Full Text Available Herbal medicines have played an important role in treating different diseases since ancient times. Bioactive components of medicinal plants are a good starting point for discovering new drugs such as chemotherapeutics. Currently, there are four classes of plant-derived chemotherapeutic drugs used in clinical practice. However, to discover new potential cytotoxic molecules, the research effort on herbal extracts has not diminished. The aim of this review was to evaluate the chemical constituents of plants that possess cytotoxicity, the signalling pathways responsible for this effect, and the influence of solvent polarity on potential cytotoxic effect and to present the cytotoxic activity of selected herbal extracts. The polyphenolic, anthraquinon, diterpneoid, triterpenoid, flavonoid, betulinic acid and berberine content contributes to cytotoxicity of herbal extracts. The inhibitory effect on cancer cells viability could be a consequence of the non-apoptotic processes, such as cell cycle arrestment, and the apoptotic process in tumour cells through different signalling pathways. The influence of solvent polarity on potential cytotoxic effect of herbal extracts should not be ignored. In general, the best cytotoxic activity was found in nonpolar and moderately polar herbal extracts. The herbal extract with IC50 below 30 μg/ml could be considered a very strong cytotoxic agent. Considering that many antitumor drugs have been discovered from natural products, further research on plants and plant-derived chemicals may result in the discovery of potent anticancer agents.

  16. Cytotoxicity of aqueous extracts of Rosmarinus officinalis L. (Labiatae) in plant test system.

    Science.gov (United States)

    Cardoso, G H S; Dantas, E B S; Sousa, F R C; Peron, A P

    2014-11-01

    This study investigated the cytotoxic activity of Rosmarinus officinalis L. (rosemary) aqueous extract on the cell cycle of Allium cepa. To this end, crude aqueous leaf extracts at four concentrations, 0.02, 0.04, 0.06 and 0.08 mg/mL, were tested on A. cepa meristematic root cells, at exposure times of 24 and 48 h. Slides were prepared by the crushing technique, and cells analyzed throughout the cell cycle, totaling 5,000 for each control group and concentration. The four concentrations tested, including the lowest and considered ideal for use, at all exposure times, showed a significant antiproliferative effect on the cell cycle of this test system and presented a high number of cells in prophase. Our results evidenced the cytotoxicity of rosemary extracts, under the studied conditions.

  17. Cytotoxicity of aqueous extracts of Rosmarinus officinalis L. (Labiatae in plant test system

    Directory of Open Access Journals (Sweden)

    GHS Cardoso

    Full Text Available This study investigated the cytotoxic activity of Rosmarinus officinalis L. (rosemary aqueous extract on the cell cycle of Allium cepa. To this end, crude aqueous leaf extracts at four concentrations, 0.02, 0.04, 0.06 and 0.08 mg/mL, were tested on A. cepa meristematic root cells, at exposure times of 24 and 48h. Slides were prepared by the crushing technique, and cells analyzed throughout the cell cycle, totaling 5,000 for each control group and concentration. The four concentrations tested, including the lowest and considered ideal for use, at all exposure times, showed a significant antiproliferative effect on the cell cycle of this test system and presented a high number of cells in prophase. Our results evidenced the cytotoxicity of rosemary extracts, under the studied conditions.

  18. Effect of cerebral hemisphere decortication on the cytotoxic activity of natural killer and natural cytotoxic lymphocytes in the mouse.

    Science.gov (United States)

    Belluardo, N; Mudò, G; Cella, S; Bindoni, M

    1990-08-06

    A comparison was made of the effects of left and right cerebral decortication on cytotoxic activity of natural killer and natural cytotoxic lymphocytes in the mouse. Natural killer cytotoxic activity was significantly reduced after right decortication, whereas left decortication led to a less pronounced, though still significant fall. The cytotoxic activity of natural cytotoxic cells, on the other hand, was significantly increased, particularly 15 days after left decortication. These findings mirror the results of previously published personal findings following electrothermocoagulation of the hypothalamus. The suggestion is made that the cortex and the hypothalamus form an integrated system for the control of certain aspects of natural immunity.

  19. Cytotoxicity Test Based on Human Cells Labeled with Fluorescent Proteins: Fluorimetry, Photography, and Scanning for High-Throughput Assay.

    Science.gov (United States)

    Kalinina, Marina A; Skvortsov, Dmitry A; Rubtsova, Maria P; Komarova, Ekaterina S; Dontsova, Olga A

    2017-12-21

    High- and medium-throughput assays are now routine methods for drug screening and toxicology investigations on mammalian cells. However, a simple and cost-effective analysis of cytotoxicity that can be carried out with commonly used laboratory equipment is still required. The developed cytotoxicity assays are based on human cell lines stably expressing eGFP, tdTomato, mCherry, or Katushka2S fluorescent proteins. Red fluorescent proteins exhibit a higher signal-to-noise ratio, due to less interference by medium autofluorescence, in comparison to green fluorescent protein. Measurements have been performed on a fluorescence scanner, a plate fluorimeter, and a camera photodocumentation system. For a 96-well plate assay, the sensitivity per well and the measurement duration were 250 cells and 15 min for the scanner, 500 cells and 2 min for the plate fluorimeter, and 1000 cells and less than 1 min for the camera detection. These sensitivities are similar to commonly used MTT (tetrazolium dye) assays. The used scanner and the camera had not been previously applied for cytotoxicity evaluation. An image processing scheme for the high-resolution scanner is proposed that significantly diminishes the number of control wells, even for a library containing fluorescent substances. The suggested cytotoxicity assay has been verified by measurements of the cytotoxicity of several well-known cytotoxic drugs and further applied to test a set of novel bacteriotoxic compounds in a medium-throughput format. The fluorescent signal of living cells is detected without disturbing them and adding any reagents, thus allowing to investigate time-dependent cytotoxicity effects on the same sample of cells. A fast, simple and cost-effective assay is suggested for cytotoxicity evaluation based on mammalian cells expressing fluorescent proteins and commonly used laboratory equipment.

  20. Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate ...

    Indian Academy of Sciences (India)

    2012-01-08

    Jan 8, 2012 ... Phenoxodiol is an isoflavone derivative that has been shown to elicit cytotoxic effects against a broad range of human cancers. We examined the effect of phenoxodiol on cell death pathways on the prostate cell lines LNCaP,. DU145 and PC3, representative of different stages of prostate cancer, and its ...

  1. In vitro cytotoxicity of indirect composite resins: Effect of storing in artificial saliva

    Directory of Open Access Journals (Sweden)

    Arzu Zeynep Yildirim-Bicer

    2013-01-01

    Full Text Available Aim: The aim of this study was to compare the cytotoxic effects of two indirect composite resins (Artglass and Solidex on the viability of L-929 fibroblast cells at different incubation periods by storing them in artificial saliva (AS. Materials and Methods: Disk-shaped test samples were prepared according to manufacturers′ instructions. Test materials were cured with light source (Dentacolor XS, Heraus Kulzer, Germany. The samples were divided into two groups. The first group′s samples were transferred into a culture medium for 1 hour, 24 hours, 72 hours, 1 week and 2 weeks. The other group′s samples were transferred into a culture medium for 1 hours, 24 hours, 72 hours, 1 week, and 2 weeks after being stored in AS for 48 hours. The eluates were obtained and pipetted for evaluation onto L-929 mouse fibroblast cultures incubated for 24 hours. Measurements were performed by MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. The degree of cytotoxicity for each sample was determined according to the reference values represented by the cells with a control group. Results: Statistical significance was determined by ANOVA. Both groups presented lower cell viability in comparison to the control group at all periods. Storing in artificial saliva reduced cytotoxicity significantly (P < 0.05. Stored Artglass and Solidex showed similar effects on cytotoxicity. Nonstored Solidex samples were found more cytotoxic than Artglass samples. The cell survival rate results of 24-hour incubation period were significantly lower than those of the other experimental periods (P < 0.05. Conclusion: Storing indirect composite resins in AS may reduce cytotoxic effects on the fibroblast cells. However, resin-based dental materials continue to release sufficient components to cause cytotoxic effects in vitro after 48 hours of storing in AS.

  2. Assessment of mutagenicity and cytotoxicity of Solanum paniculatum L. extracts using in vivo micronucleus test in mice

    Directory of Open Access Journals (Sweden)

    PM. Vieira

    Full Text Available Solanum paniculatum L. is a plant species widespread throughout tropical America, especially in the Brazilian Savanna region. It is used in Brazil for culinary purposes and in folk medicine to treat liver and gastric dysfunctions, as well as hangovers. Because of the wide use of this plant as a therapeutic resource and food, the present study aimed at evaluating the mutagenic and cytotoxic effects of S. paniculatum ethanolic leaf and fruit extracts using the mouse bone marrow micronucleus test. Our results indicate that neither S. paniculatum ethanolic leaf extract nor its ethanolic fruit extract exhibited mutagenic effect in mice bone marrow; however, at higher doses, both extracts presented cytotoxic activity.

  3. Cytotoxic effects of Albendazole, antiparasitic drug, on the liver

    African Journals Online (AJOL)

    Printed in Egypt. El Harmeen Press, Cairo. (EBB Soc). Cytotoxic effects of Albendazole, antiparasitic drug, on the liver of the rat: Sub- chronic study. Mohamed A Abd El-Rahmanl, Ismail M Abdel-Nabil, Mohamed A Oman“ and. Moustafa F Mohamed2 l. Zoology Department, Faculty of Science, Suez Canal University, Ismailia, ...

  4. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer ...

    Indian Academy of Sciences (India)

    Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness forpreventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activityof silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial ...

  5. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer ...

    Indian Academy of Sciences (India)

    2016-12-16

    Dec 16, 2016 ... Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder ...

  6. Evaluation of Cytotoxicity and Antifertility Effect of Artemisia kopetdaghensis

    Directory of Open Access Journals (Sweden)

    Davood Oliaee

    2014-01-01

    Full Text Available To date, there is no report on safety of Artemisia Kopetdaghensis. This study aimed to determine the possible undesirable effects of A. Kopetdaghensis on reproduction of female rats. The pregnant rats were treated (i.p. with vehicle or 200 and 400 mg/kg of A. Kopetdaghensis hydroalcoholic extract from the 2nd to 8th day of pregnancy. Then, number and weight of neonates, duration of pregnancy, and percent of dead fetuses were determined. Also, cytotoxicity of this plant was tested using fibroblast (L929 and ovary (Cho cell lines. The A. Kopetdaghensis had no significant effect on duration of pregnancy, average number of neonates, and weight of neonates. However, administration of 200 and 400 mg/kg of the extract led to 30 and 44% abortion in animals, respectively. The extract at concentrations ≥200 μg/mL significantly (P<0.001 inhibited the proliferation of L929 fibroblast cells. Regarding the Cho cells, the extract induced toxicity only at concentration of 800 μg/mL (P<0.01. Our results showed that continuous consumption of A. Kopetdaghensis in pregnancy may increase the risk of abortion and also may have toxic effect on some cells.

  7. Evaluation of Cytotoxicity and Antifertility Effect of Artemisia kopetdaghensis.

    Science.gov (United States)

    Oliaee, Davood; Boroushaki, Mohammad Taher; Oliaee, Naiime; Ghorbani, Ahmad

    2014-01-01

    To date, there is no report on safety of Artemisia Kopetdaghensis. This study aimed to determine the possible undesirable effects of A. Kopetdaghensis on reproduction of female rats. The pregnant rats were treated (i.p.) with vehicle or 200 and 400 mg/kg of A. Kopetdaghensis hydroalcoholic extract from the 2nd to 8th day of pregnancy. Then, number and weight of neonates, duration of pregnancy, and percent of dead fetuses were determined. Also, cytotoxicity of this plant was tested using fibroblast (L929) and ovary (Cho) cell lines. The A. Kopetdaghensis had no significant effect on duration of pregnancy, average number of neonates, and weight of neonates. However, administration of 200 and 400 mg/kg of the extract led to 30 and 44% abortion in animals, respectively. The extract at concentrations ≥200 μg/mL significantly (P < 0.001) inhibited the proliferation of L929 fibroblast cells. Regarding the Cho cells, the extract induced toxicity only at concentration of 800 μg/mL (P < 0.01). Our results showed that continuous consumption of A. Kopetdaghensis in pregnancy may increase the risk of abortion and also may have toxic effect on some cells.

  8. Ethnobotanical survey and cytotoxicity testing of plants of South-western Nigeria used to treat cancer, with isolation of cytotoxic constituents from Cajanus cajan Millsp. leaves.

    Science.gov (United States)

    Ashidi, J S; Houghton, P J; Hylands, P J; Efferth, T

    2010-03-24

    dichloromethane fraction of Cajanus cajan had IC(50) value 5-10 microg/mL, with the two constituent stilbenes, longistylins A and C, being primarily responsible, with IC(50) values of 0.7-14.7 microM against the range of cancer cell lines. Most of the species tested had some cytotoxic effect on the cancer cell lines, which to some extent supports their traditional inclusion in herbal preparations for treatment of cancer. However, little selectivity for cancer cells was observed, which raises concerns over their safety and efficacy in traditional treatment. The longistylins A and C appear to be responsible for much of the activity of Cajanus cajan extract. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Effect of different forms of anionic nanoclays on cytotoxicity.

    Science.gov (United States)

    Baek, Miri; Kim, In-Sun; Yu, Jin; Chung, Hae Eun; Choy, Jin-Ho; Choi, Soo-Jin

    2011-02-01

    Anionic nanoclays, so-called layered double hydroxide (LDH) nanoparticles, have been extensively applied as drug delivery systems, since they efficiently enter cells via endocytosis pathway and possess controlled release property. However, the stability of LDHs varies, depending on the type of interlayer anions, which can also affect their toxicity. In this study, we investigated the effects of two different forms of LDH, carbonate form (MgAl-LDH-CO3) and chloride form (MgAl-LDH-Cl), on cytotoxicity in human lung epithelial cells. The result showed that MgAl-LDH-Cl was more easily dissolved into metal ions under simulated lysosomal (pH 4.5) and body fluid (pH 7.4) conditions than did MgAl-LDH-CO3. According to cytotoxicity evaluation, MgAl-LDH-CO3 exhibited high toxicity compared with MgAl-LDH-Cl in terms of induction of oxidative stress, apoptosis and membrane damage. These results suggest that easily dissoluble MgAl-LDH-Cl has low cytotoxicity, while high stability of MgAl-LDH-CO3 is correlated to elevated cytotoxicity.

  10. Acute cytotoxic effects of marketed ophthalmic formulations on human corneal epithelial cells.

    Science.gov (United States)

    Hakkarainen, Jenni J; Reinisalo, Mika; Ragauskas, Symantas; Seppänen, Aila; Kaja, Simon; Kalesnykas, Giedrius

    2016-09-10

    The purpose of the study was to devise a fast, reliable and sensitive cell viability assay for assessment of acute cytotoxicity on human corneal epithelial cells by using a clinically relevant exposure time. Acute cytotoxic effects of the pharmaceutical excipients benzalkonium chloride (BAC), macrogolglycerol hydroxystearate (MGHS40), polysorbate 80 (PS80) and marketed ophthalmic formulations (Lumigan(®), Monoprost(®), Taflotan(®), Travatan(®), Xalatan(®)) containing these excipients were tested. Human corneal epithelial cell (HCE-T) viability was assessed by measuring the reduction of resazurin to highly fluorescent resorufin. Expression of the tight junction proteins in HCE-T cells were characterized by immunofluorescence staining. Presence of tight junction proteins in HCE-T cells was demonstrated. BAC preserved ophthalmic formulations showed concentration-dependent and time-dependent cytotoxicity to human corneal epithelium. In contrast, no acute cytotoxicity of non-ionic stabilizing/solubilizing excipients (MGSH40 and PS80) or ophthalmic formulation containing these excipients was observed. Marketed ophthalmic formulations used for glaucoma medication show differential toxicity on human corneal epithelial cells. The present study revealed that BAC-preserved ophthalmic formulations were able to induce acute cytotoxic effects even during a clinically relevant exposure time, which was not observed with MGSH40 and PS80 excipients or ophthalmic formulations containing these excipients. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Bactericidal and cytotoxic effects of Erythrina fusca leaves aquadest extract

    Directory of Open Access Journals (Sweden)

    Janti Sudiono

    2013-03-01

    Full Text Available Background: Empirically, Erythrina fusca has been used as traditional herb for its antibacterial and antiinflammation properties. Periodontal disease is one of the most oral infectious diseases with microorganism predominated as the contributing factors. Porphyromonas gingivalis (P. gingivalis is one of the main bacteria pathogen found in periodontal diseases. Purpose: The purpose of this study was to examine the bactericidal effect of Erythrina fusca Leaves Aquadest Extract (EFLAE at various concentrations on P. gingivalis and cytotoxic effect on fibroblast. Methods: Pure P. gingivalis was cultured in Brain Heart Infusion (BHI medium for 24 hours with or without various concentrations of treatment of EFLAE. Calculation and statistical analysis of remaining bacteria were performed by inhibitory zone method to evaluate the EFLAE bactericidal effect and compared to chlorhexidine as positive control. To evaluate the cytotoxic effect, NIH 3T3 cells were cultured in Dulbecco’s Modification of Eagle’s Medium (DMEM containing of 10% fetal bovine serum (FBS and 1% penicillin-streptomycin, pH 7.2, in 5% CO2, and stored in humidified incubator under temperature 370 C. Cells were treated with/without various concentrations of EFLAE for 48 hours. The viable cells were then counted using 3-(4,5- Dimethylthiazol-2-yl-2,5 diphenyl tetrazodium bromide (MTT method. Results: EFLAE have bactericidal effect on P. gingivalis in a concentration dependent manner starting from 78%. The concentration of 90% EFLAE had stronger bactericidal effect (35.004 ± 1.546 than those of chlorhexidine as positive control (32.313 ± 1.619. One-way ANOVA showed significant bactericidal effect differences among concentrations of EFLAE and chlorhexidine (p<0.05 while Tuckey HSD test showed significant difference only between lower concentration of EFLAE (78%, 79% and chlorhexidine. With the highest concentration of EFLAE (100% applied in the bactericidal test, no cytotoxic effect

  12. The inhibition effect of non-protein thiols on dentinal matrix metalloproteinase activity and HEMA cytotoxicity.

    Science.gov (United States)

    Nassar, Mohannad; Hiraishi, Noriko; Shimokawa, Hitoyata; Tamura, Yukihiko; Otsuki, Masayuki; Kasugai, Shohei; Ohya, Keiichi; Tagami, Junji

    2014-03-01

    Phosphoric acid (PA) etching used in etch-and-rinse adhesives is known to activate host-derived dentinal matrix-metalloproteinases (MMPs) and increase dentinal permeability. These two phenomena will result, respectively; in degradation of dentine-adhesive bond and leaching of some monomers especially 2-hydroxyethyl methacrylate (HEMA) into the pulp that would negatively affect the viability of pulpal cells. This study is the first to investigate the inhibitory effect of non-protein thiols (NPSH); namely reduced glutathione (GSH) and N-acetylcysteine (NAC) on dentinal MMPs and compare their effects on HEMA cytotoxicity. Dentine powder was prepared from human teeth, demineralized with 1% PA and then treated with 2% GSH, 2% NAC or 2% chlorhexidine (CHX). Zymographic analysis of extracted proteins was performed. To evaluate the effect of GSH, NAC and CHX on HEMA cytotoxicity, solutions of these compounds were prepared with or without HEMA and rat pulpal cells were treated with the tested solutions for (6 and 24h). Cells viability was measured by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytotoxicity data were analysed by one-way ANOVA and Tukey post hoc tests (peffect of GSH and NAC on dentinal MMPs was confirmed. GSH showed similar effectiveness to NAC regarding HEMA cytotoxicity inhibition. NPSH were effective to inhibit dentinal MMPs and HEMA cytotoxicity. The tested properties of NPSH provide promising clinical use of these agents which would enhance dentine-bond durability and decrease post-operative sensitivity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Effect of size and processing method on the cytotoxicity of realgar nanoparticles in cancer cell lines.

    Science.gov (United States)

    Zhao, Weizhong; Lu, Xun; Yuan, Yuan; Liu, Changsheng; Yang, Baican; Hong, Hua; Wang, Guoying; Zeng, Fanyan

    2011-01-01

    In this study, the effects of the size and Chinese traditional processing (including elutriation, water cleaning, acid cleaning, alkali cleaning) on realgar nanoparticles (RN)-induced antitumor activity in human osteosarcoma cell lines (MG-63) and hepatoma carcinoma cell lines (HepG-2) were investigated. The human normal liver cell line (L-02) was used as control. RN was prepared by high-energy ball milling technology. The results showed that with the assistance of sodium dodecyl sulfate, the size of realgar could be reduced to 127 nm after 12 hours' ball milling. The surface charge was decreased from 0.83 eV to -17.85 eV and the content of As₂O₃ clearly increased. Except for elutriation, the processing methods did not clearly change the size of the RN, but the content of As₂O₃ was reduced dramatically. In vitro MTT tests indicated that in the two cancer cell lines, RN cytotoxicity was more intense than that of the coarse realgar nanoparticles, and cytotoxicity was typically time- and concentration-dependent. Also, RN cytotoxicities in the HepG-2 and L-02 cells all increased with increasing milling time. Due to the reduction of the As₂O₃ content, water cleaning, acid cleaning, and alkali cleaning decreased RN cytotoxicity in HepG-2, but RN after elutriation, with the lowest As₂O₃ (3.5 mg/g) and the smallest size (109.3 nm), showed comparable cytotoxicity in HepG-2 to RN without treatment. Meanwhile, RN-induced cytotoxicity in L-02 cells was clearly reduced. Therefore, it can be concluded that RN may provide a strong antiproliferation effect in the MG-63 and HepG-2 cells. Elutriation processing is a suitable approach to limit the dangerous side-effects of As₂O₃, while maintaining the effectiveness of RN.

  14. Cytotoxicity and apoptogenic effects of Lafoensia pacari.

    Science.gov (United States)

    da Silva Marcondes, Daniela Beck; Reichert, Cristiane Loiva; de Andrade, Lucas Ferrari; de Moraes Santos, Cid Aimbiré; Weffort-Santos, Almeriane Maria

    2014-11-18

    The stem barks of Lafoensia pacari have been traditionally used not only by South Amerindians but also by Brazilian and Paraguayan populations for treating a variety of unhealthy conditions to which their biological potential has been scientifically documented in several reports over the last decade. Although its anticancer usage is also popular, no scientific support for such activity has been found. To provide scientific evidence for the anticancer popularity of Lafoensia pacari. Extracts prepared according to the popular use along with a methanol extract and its four fractions were produced from Lafoensia pacari stem barks. The chromatogram profile of each one was obtained by HPLC. Several tumor cell lines were exposed to these solutions in in vitro assays and the effects evaluated by morphological, growth, and cell cycle status changes. High toxicity determined by the lactate dehydrogenase levels with a significant drop in the cell proliferation index were found for all cell lines included in this study after exposition to Lafoensia pacari extract and fractions. The morphological features along with the expression of annexin V have strongly suggested apoptosis induction, which has been confirmed by G0/G1 cell cycle arrest. The data have clearly shown that exposition of human tumor cell lines to Lafoensia pacari stem barks extract leads to apoptosis induction due to cell cycle arrest in G0/G1 phases, supporting its anticancer use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Evaluation of cell cytotoxic effect on herbal extracts mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Soo; Gwon, Hui Jeong; Choi, Bo Ram; Lim, Youn Mook; Nho, Young Chang [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2009-12-15

    Herbal extracts (HE) such as Houttuynia cordata Thunb., Eucommia ulimoides, Plantago asiatica var., Morus alba L., and Ulmus davidiana var., are known to suppress an atopic dermatitis like skin lesions. In this study, to evaluate the cell cytotoxicity effect on L929, HaCaT and HMC-1 cell by the HE, the herbs were extracted with distilled water (at 75 .deg. C) and then the HE mixtures were freeze-dried for 5 days and sterilized with {gamma}-rays. The cytotoxicity was measured by Cell Counting Kit-8 (CCK-8) assay. The result showed that the HE mixtures did not significantly affect cell viability and had no toxicity on the cells. These findings indicate that the HE mixtures can be used as a potential therapeutic agent.

  16. Effect of post-polymerization heat treatments on the cytotoxicity of two denture base acrylic resins.

    Science.gov (United States)

    Jorge, Janaina Habib; Giampaolo, Eunice Teresinha; Vergani, Carlos Eduardo; Machado, Ana Lúcia; Pavarina, Ana Cláudia; Carlos, Iracilda Zeppone

    2006-06-01

    Most denture base acrylic resins have polymethylmethacrylate in their composition. Several authors have discussed the polymerization process involved in converting monomer into polymer because adequate polymerization is a crucial factor in optimizing the physical properties and biocompatibility of denture base acrylic resins. To ensure the safety of these materials, in vitro cytotoxicity assays have been developed as preliminary screening tests to evaluate material biocompatibility. (3)H-thymidine incorporation test, which measures the number of cells synthesizing DNA, is one of the biological assays suggested for cytotoxicity testing. The purpose of this study was to investigate, using (3)H-thymidine incorporation test, the effect of microwave and water-bath post-polymerization heat treatments on the cytotoxicity of two denture base acrylic resins. Nine disc-shaped specimens (10 x 1 mm) of each denture base resin (Lucitone 550 and QC 20) were prepared according to the manufacturers' recommendations and stored in distilled water at 37 degrees C for 48 h. The specimens were assigned to 3 groups: 1) post-polymerization in a microwave oven for 3 min at 500 W; 2) post-polymerization in water-bath at 55 degrees C for 60 min; and 3) without post-polymerization. For preparation of eluates, 3 discs were placed into a sterile glass vial with 9 mL of Eagle's medium and incubated at 37 degrees C for 24 h. The cytotoxic effect of the eluates was evaluated by (3)H-thymidine incorporation. The results showed that the components leached from the resins were cytotoxic to L929 cells, except for the specimens heat treated in water bath (pmicrowave post-polymerization heat treatment.

  17. Cytotoxic and genotoxic effects of abamectin, chlorfenapyr, and imidacloprid on CHOK1 cells.

    Science.gov (United States)

    Al-Sarar, Ali S; Abobakr, Yasser; Bayoumi, Alaa E; Hussein, Hamdy I

    2015-11-01

    The cytotoxicity and genotoxicity of abamectin, chlorfenapyr, and imidacloprid have been evaluated on the Chinese hamster ovary (CHOK1) cells. Neutral red incorporation (NRI), total cellular protein content (TCP), and methyl tetrazolium (MTT) assays were followed to estimate the mid-point cytotoxicity values, NRI50, TCP50, and MTT50, respectively. The effects of the sublethal concentration (NRI25) on glutathione S-transferase (GST), glutathione reductase (GRD), glutathione peroxidase (GPX), and total glutathione content have been evaluated in the presence and absence of reduced glutathione (GSH), vitamin C, and vitamin E. The genotoxicity was evaluated using chromosomal aberrations (CA), micronucleus (MN) formation, and DNA fragmentation techniques in the presence and absence of the metabolic activation system, S9 mix. Abamectin was the most cytotoxic pesticide followed by chlorfenapyr, while imidacloprid was the least cytotoxic one. The glutathione redox cycle components were altered by the tested pesticides in the absence and presence of the tested antioxidants. The results of genotoxicity indicate that abamectin, chlorfenapyr, and imidacloprid have potential genotoxic effects on CHOK1 cells under the experimental conditions.

  18. Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and phospholipidosis

    Directory of Open Access Journals (Sweden)

    A. Vejux

    2008-07-01

    Full Text Available Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic oxidation of cholesterol. They are present in numerous foodstuffs and have been demonstrated to be present at increased levels in the plasma of patients with cardiovascular diseases and in atherosclerotic lesions. Thus, their role in lipid disorders is widely suspected, and they might also be involved in important degenerative diseases such as Alzheimer's disease, osteoporosis, and age-related macular degeneration. Since atherosclerosis is associated with the presence of apoptotic cells and with oxidative and inflammatory processes, the ability of some oxysterols, especially 7-ketocholesterol and 7β-hydroxycholesterol, to trigger cell death, activate inflammation, and modulate lipid homeostasis is being extensively studied, especially in vitro. Thus, since there are a number of essential considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols, it is important to determine their biological activities and identify their signaling pathways, when they are used either alone or as mixtures. Oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or none whatsoever. Moreover, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures has been observed with cytotoxic oxysterols, suggesting that cytotoxic oxysterols are potent inducers of phospholipidosis. This basic knowledge about oxysterols contributes to a better understanding of the associated pathologies and may lead to new treatments and new drugs. Since oxysterols have a number of biological activities, and as oxysterol-induced cell death is assumed to take part in degenerative pathologies, the present review will focus on the cytotoxic activities of these compounds, the corresponding cell death signaling pathways, and associated events (oxidation, inflammation, and phospholipidosis.

  19. Cytotoxicity and Effects on Cell Viability of Nickel Nanowires

    KAUST Repository

    Rodriguez, Jose E.

    2013-05-01

    Recently, magnetic nanoparticles are finding an increased use in biomedical applications and research. Nanobeads are widely used for cell separation, biosensing and cancer therapy, among others. Due to their properties, nanowires (NWs) are gaining ground for similar applications and, as with all biomaterials, their cytotoxicity is an important factor to be considered before conducting biological studies with them. In this work, the cytotoxic effects of nickel NWs (Ni NWs) were investigated in terms of cell viability and damage to the cellular membrane. Ni NWs with an average diameter of 30-34 nm were prepared by electrodeposition in nanoporous alumina templates. The templates were obtained by a two-step anodization process with oxalic acid on an aluminum substrate. Characterization of NWs was done using X-Ray diffraction (XRD) and energy dispersive X-Ray analysis (EDAX), whereas their morphology was observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cell viability studies were carried out on human colorectal carcinoma cells HCT 116 by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cell proliferation colorimetric assay, whereas the lactate dehydrogenase (LDH) homogenous membrane fluorimetric assay was used to measure the degree of cell membrane rupture. The density of cell seeding was calculated to obtain a specific cell number and confluency before treatment with NWs. Optical readings of the cell-reduced MTT products were measured at 570 nm, whereas fluorescent LDH membrane leakage was recorded with an excitation wavelength of 525 nm and an emission wavelength of 580 - 640 nm. The effects of NW length, cell exposure time, as well as NW:cell ratio, were evaluated through both cytotoxic assays. The results show that cell viability due to Ni NWs is affected depending on both exposure time and NW number. On the other hand, membrane rupture and leakage was only significant at later exposure times. Both

  20. Cytotoxic Effect of Lipophilic Bismuth Dimercaptopropanol Nanoparticles on Epithelial Cells.

    Science.gov (United States)

    Rene, Hernandez-Delgadillo; Badireddy, Appala Raju; José, Martínez-Sanmiguel Juan; Francisco, Contreras-Cordero Juan; Israel, Martinez-Gonzalez Gustavo; Isela, Sánchez-Nájera Rosa; Chellam, Shankararaman; Claudio, Cabral-Romero

    2016-01-01

    Bismuth nanoparticles have many interesting properties to be applied in biomedical and medicinal sectors, however their safety in humans have not been comprehensively investigated. The objective of this research was to determine the cytotoxic effect of bismuth dimercaptopropanol nanoparticles (BisBAL NPs) on epithelial cells. The nanoparticles are composed of 18.7 nm crystallites on average and have a rhombohedral structure, agglomerating into chains-like or clusters of small nanoparticles. Based on MTT viability assay and fluorescence microscopy, cytotoxicity was not observed on monkey kidney cells after growing with 5 µM of BisBAL NPs for 24 h. Employing same techniques, identical results were obtained with human epithelial cells (HeLa), showing a not strain-dependent phenomenon. The absence of toxic effects on epithelial cells growing with BisBAL NPs was corroborated with long-time experiments (24-72 hrs.), showing no difference in comparison with growing control (cells without nanoparticles). Further, genotoxicity assays, comet assay and fluorescent microscopy and electrophoresis in bromide-stained agarose gel revealed no damage to genomic DNA of MA104 cells after 24 h. of exposition to BisBAL NPs. Finally, the effect of bismuth nanoparticles on protein synthesis was studied in cells growing with BisBAL NPs for 24 h. SDS-PAGE assays showed no difference between treated and untreated cells, suggesting that BisBAL NPs did not interfere with protein synthesis. Hence BisBAL NPs do not appear to exert cytotoxic effects suggesting their biological compatibility with epithelial cells.

  1. Cytotoxicity and antiangiogenic effects of Rhus coriaria, Pistacia vera and Pistacia khinjuk oleoresin methanol extracts.

    Science.gov (United States)

    Mirian, M; Behrooeian, M; Ghanadian, M; Dana, N; Sadeghi-Aliabadi, H

    2015-01-01

    Angiogenesis, formation of new blood vessels, play an important role in some diseases such as cancer and its metastasis. Using angiogenesis inhibitors, therefore, is one of the ways for cancer treatment and prevention of metastasis. Medicinal plants have been shown to play a major role in the treatment of a variety of cancers. In this direction, cytotoxic and angiogenic effects of oleo gum resin extracts of Rhus coriaria, Pistacia vera and Pistacia khinjuk from Anacardiaceae family were studied. For IC50 values, cytotoxic effects of the plant extracts were evaluated at different concentrations (1, 10, 20, 40, 80,100 μg/ml) against human umbilical vein endothelial normal cell (HUVEC) and Y79 cell lines using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In vitro tube formation on matrigel base was used to evaluate angiogenic effects in the presence of increasing concentrations (50, 100, 250 μg/ml) of the extracts. Vascular endothelium growth factor was used as angiogenesis stimulator. Gas chromatography results showed that α-pinene and β-pinene were the major essential oils constituents of all plant extracts. According to the MTT assay results, the R. coriaria resin extract was more cytotoxic than those of P. vera and P. khinjuk extracts (IC50, 9.1 ± 1.6 vs 9.8 ± 2.1 and 12.0 ± 1.9, respectively; P<0.05). Cytotoxic effects of all extracts against Y79 cell line was significantly higher than those of HUVEC used as a normal cell line (P<0.05). Tube formation assay also showed that extract of R. coriaria resin inhibited angiogenesis more significantly than other tested extracts (P<0.05). It could be concluded that R. coriaria resin extract possess cytotoxic effect and antiangiogenesis against cancer cells and as an anticancer natural product has a good potential for future studies.

  2. Cytotoxic effects of Euterpe oleracea Mart. in malignant cell lines.

    Science.gov (United States)

    Silva, Dulcelena Ferreira; Vidal, Flávia Castello Branco; Santos, Debora; Costa, Maria Célia Pires; Morgado-Díaz, José Andrés; do Desterro Soares Brandão Nascimento, Maria; de Moura, Roberto Soares

    2014-05-29

    Euterpe oleracea Mart., a plant from the Amazon region, is commonly known as açaí or juçara; it has high nutritional value and elevated levels of lipids, proteins, and minerals. Açaí is an abundant and much consumed fruit by the Amazon local population, and studies have demonstrated that it is rich in phytochemicals with antioxidant, anti-inflammatory, and anticancer activities. Therefore, the aim of this study was to test this plant for anticancer activity in different human malignant cell lines. Cell lines derived from breast and colorectal adenocarcinomas were treated with 10, 20, and 40 μg/mL of bark, seed, and total açaí fruit hydroalcoholic extracts for 24 and 48 h. After treatment, cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and cell morphological features were observed by light and transmission electron microscopy. The type of cell death was also evaluated. The data were analyzed statistically by one-way analysis of variance (ANOVA), followed by Dunnett's or Tukey's post hoc tests, as appropriate. We observed that of all the cell lines tested, MCF-7 was the only line that responded to açaí treatment. The extracts caused significant reduction (p<0.01) in cell viability and altered cell morphological features by inducing the appearance of autophagic vacuoles, as observed by transmission electron microscopy. Furthermore, increased expression of LC3BII, a protein marker of autophagosome formation, was observed by western blotting. Caspase Glo™ assays and morphologic observations by DAPI nuclear staining and transmission electron microscopy did not indicate any apoptotic events. The present study demonstrated that açaí possesses antitumorigenic potential in the MCF-7 cell line. Further studies are needed to identify the compound (s) responsible for this cytotoxic activity and the molecular target in the cell. This discovery of the anticancer potential of açaí may help in the

  3. Cytotoxic effects of Oosporein isolated from endophytic fungus Cochliobolus kusanoi

    Directory of Open Access Journals (Sweden)

    Rmaesha eA

    2015-09-01

    Full Text Available In the present study, oosporein, a fungal toxic secondary metabolite known to be a toxic agent causing chronic disorders in animals, was isolated from fungus Cochliobolus kusanoi of Nerium oleander L. Toxic effects of oosporein and the possible mechanisms of cytotoxicity as well as the role of oxidative stress in cytotoxicity to MDCK kidney cells and RAW 264.7 splene cells were evaluated in-vitro. Also to know the possible in-vivo toxic effects of oosporein on kidney and spleen, Balb/C mouse were treated with different concentrations of oosporein ranging from 20 uM to 200 µM. After 24 hrs of post exposure histopathological observations were made to know the effects of oosporein on target organs. Oosporein induced elevated levels of ROS generation and high levels of MDA, loss of mitochondrial membrane potential (MMP, induced glutathione hydroxylase production was observed in a dose depended manner. Effects oosporein on chromosomal DNA damage was assessed by Comet assay, and increase in DNA damage were observed in both the studied cell lines by increasing the oosprin concentration. Further, oosporein treatment to studied cell lines indicated significant suppression of oxidative stress related gene (SOD1 and CAT expression, and increased levels of mRNA expression in apoptosis or oxidative stress

  4. Cytotoxic effects of nickel nanowires in human fibroblasts

    KAUST Repository

    Felix Servin, Laura P.

    2016-03-09

    The increasing interest in the use of magnetic nanostructures for biomedical applications necessitates rigorous studies to be carried out in order to determine their potential toxicity. This work attempts to elucidate the cytotoxic effects of nickel nanowires (NWs) in human fibroblasts WI-38 by a colorimetric assay (MTT) under two different parameters: NW concentration and exposure time. This was complemented with TEM and confocal images to assess the NWs internalization and to identify any changes in the cell morphology. Ni NWs were fabricated by electrodeposition using porous alumina templates. Energy dispersive X-Ray analysis, scanning electron microscopy and transmission electron microscopy imaging were used for NW characterization. The results showed decreased cell metabolic activity for incubation times longer than 24 hours and no negative effects for exposure times shorter than that. The cytotoxicity effects for human fibroblasts were then compared with those reported for HCT 116 cells, and the findings point out that it is relevant to consider the cellular size. In addition, the present study compares the toxic effects of equivalent amounts of nickel in the form of its salt to those of NWs and shows that the NWs are more toxic than the salts. Internalized NWs were found in vesicles inside of the cells where their presence induced inflammation of the endoplasmic reticulum.

  5. The Protective Effect of Silybin against Lasalocid Cytotoxic Exposure on Chicken and Rat Cell Lines

    Directory of Open Access Journals (Sweden)

    Lidia Radko

    2013-01-01

    Full Text Available Lasalocid, an ionophore coccidiostat, extensive use implies a risk of toxicological impacts. Protective effects of silybin, a herbal compound of Silybum marianum, are reported elsewhere. The aim of this study was to compare effects of the combined use of lasalocid and silybin in chicken hepatoma cells (LMH and rat myoblasts (L6 cell lines cultures. The cytoprotective effect resulting from an interaction of both pharmaceuticals was measured with the help of MTT reduction and, coomassie brilliant blue binding (CBB and LDH release assays. Isobolography and the combination index (CI estimated the nature and scale of interaction. In all performed tests, the lowest lasalocid EC50-values were obtained for chicken hepatocytes. In the rat myoblasts cultures, the lowest lasalocid EC50-values were found with LDH test. Simultaneously, a lack of silybin cytotoxic effect was proven for the studied cell lines. An interaction between both substances led to a considerable decrease of lasalocid cytotoxicity. The isobolograms and combination index showed a significant antagonistic nature of silybin effect in the course of lasalocid cytotoxicity. It is concluded that the mechanism of cytoprotection results from complex reaction at biochemical and biophysical endpoints during chicken hepatocytes and rat myoblasts cell lines exposure to silybin and lasalocid co-action.

  6. Cytotoxic Effects of Nickel Nanowires in Human Fibroblasts

    KAUST Repository

    Felix Servin, Laura P.

    2014-04-01

    There is an increasing interest for the use of nanostructures as potential tools in areas that include biology and medicine, for applications spanning from cell separation to treatments of diseases. Magnetic nanoparticles (MNPs) have been the most widely studied and utilized nanostructures in biomedical applications. Despite their popularity, the regular shape of MNPs limits their potential for certain applications. Studies have shown that magnetic nanowires (MNWs), due to their high-­‐aspect ratio and specific magnetic properties, might provide improved performance for some biomedical applications. As a consequence, MNWs have received increasing attention from researchers in the last years. However, as with any other nanostructure intended for biomedical applications, rigorous studies must be carried out to determine their potential toxicity and adverse effects before they can be successfully incorporated in clinical applications. This work attempts to elucidate the cytotoxic effects of nickel NWs (Ni NWs) in human fibroblasts by measuring cell viability under different parameters. Ni NWs of three different lengths (0.86 ± 0.02 μm, 1.1 ± 0.1 μm and 6.1 ± 0.6 μm) were fabricated by electrodeposition using porous aluminum oxide (PAO) membranes as templates. Energy dispersive X-­‐Ray analysis (EDAX) and X-­‐Ray diffraction (XRD) were used for the chemical characterization of the Ni NWs. Their physical characterization was done using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) imaging. MTT assays were performed to assess cell viability of human fibroblasts in the presence of Ni NWs. NW length, NW/cell ratio and exposure time were changed throughout the experiments to elucidate their effects on cell viability. The results showed that NWs length has a strong effect on internalization and cytotoxicity. Smaller NWs showed higher toxicity levels at earlier times while longer NWs had stronger effects on cell viability at

  7. Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes

    NARCIS (Netherlands)

    Donatus, I A; Sardjoko,; Vermeulen, N P

    1990-01-01

    The cytoprotective effect of curcumin, a natural constituent of Curcuma longa, on the cytotoxicity of paracetamol in rat hepatocytes was studied. Paracetamol was selected as a model-toxin, since it is known to be bioactivated by 3-methylcholanthrene inducible cytochromes P450 presumably to

  8. Determining the size and concentration dependence of gold nanoparticles in vitro cytotoxicity (IC50) test using WST-1 assay

    Science.gov (United States)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul; Aziz, Azlan Abdul; Shamsuddin, Shaharum

    2015-04-01

    Gold nanoparticles (AuNPs) received a great deal of attention for biomedical applications, especially in diagnostic imaging and therapeutics. Even though AuNPs have potential benefits in biomedical applications, the impact of AuNPs on human and environmental health still remains unclear. The use of AuNPs which is a high-atomic-number materials, provide advantages in terms of radiation dose enhancement. However, before this can become a clinical reality, cytotoxicity of the AuNPs has to be carefully evaluated. Cytotoxicity test is a rapid, standardized test that is very sensitive to determine whether the nanoparticles produced are harmful or benign on cellular components. In this work the size and concentration dependence of AuNPs cytotoxicity in breast cancer cell lines (MCF-7) are tested by using WST-1 assay. The sizes of AuNPs tested were 13 nm, 50 nm, and 70 nm. The cells were seeded in the 96-well plate and were treated with different concentrations of AuNPs by serial dilution for each size of AuNPs. The high concentration of AuNPs exhibit lower cell viability compared to low concentration of AuNPs. We quantified the toxicity of AuNPs in MCF-7 cell lines by determining the IC50 values in WST-1 assays. The IC50 values (inhibitory concentrations that effected 50% growth inhibition) of 50 nm AuNPs is lower than 13 nm and 70 nm AuNPs. Mean that, 50nm AuNPs are more toxic to the MCF-7 cells compared to smaller and larger sizes AuNPs. The presented results clearly indicate that the cytotoxicity of AuNPs depend not only on the concentration, but also the size of the nanoparticles.

  9. Cytotoxic effects of oosporein isolated from endophytic fungus Cochliobolus kusanoi.

    Science.gov (United States)

    Ramesha, Alurappa; Venkataramana, M; Nirmaladevi, Dhamodaran; Gupta, Vijai K; Chandranayaka, S; Srinivas, Chowdappa

    2015-01-01

    In the present study, oosporein, a fungal toxic secondary metabolite known to be a toxic agent causing chronic disorders in animals, was isolated from fungus Cochliobolus kusanoi of Nerium oleander L. Toxic effects of oosporein and the possible mechanisms of cytotoxicity as well as the role of oxidative stress in cytotoxicity to Madin-Darby canine kidney kidney cells and RAW 264.7 splene cells were evaluated in vitro. Also to know the possible in vivo toxic effects of oosporein on kidney and spleen, Balb/C mouse were treated with different concentrations of oosporein ranging from 20 to 200 μM). After 24 h of exposure histopathological observations were made to know the effects of oosporein on target organs. Oosporein induced elevated levels of reactive oxygen species (ROS) generation and high levels of malondialdehyde, loss of mitochondrial membrane potential, induced glutathione hydroxylase (GSH) production was observed in a dose depended manner. Effects oosporein on chromosomal DNA damage was assessed by Comet assay, and increase in DNA damage were observed in both the studied cell lines by increasing the oosporein concentration. Further, oosporein treatment to studied cell lines indicated significant suppression of oxidative stress related gene (Superoxide dismutase1 and Catalase ) expression, and increased levels of mRNA expression in apoptosis or oxidative stress inducing genes HSP70, Caspase3, Caspase6, and Caspase9 as measured by quantitative real time-PCR assay. Histopathological examination of oosporein treated mouse kidney and splenocytes further revealed that, oosporein treated target mouse tissues were significantly damaged with that of untreated sam control mice and these effects were in directly proportional to the the toxin dose. Results of the present study reveals that, ROS is the principle event prompting increased oosporein toxicity in studied in vivio and in vitro animal models. The high previlance of these fungi in temperate climates further

  10. Cytotoxic effect of a new endodontic cement and mineral trioxide aggregate on L929 line culture

    Science.gov (United States)

    Ghoddusi, Jamileh; Tavakkol Afshari, Jalil; Donyavi, Zakiyeh; Brook, Azam; Disfani, Reza; Esmaeelzadeh, Mohammad

    2008-01-01

    Introduction: The aim of this study was to compare the cytotoxicity of Mineral Trioxide Aggregate (MTA) and a New Endodontic Cement (NEC) on L929 mouse fibroblasts. Materials and Methods: Different dilutions (Neat, 1/2, 1/10, 1/100) of fresh and set materials placed adjacent flasks of L929 in DMEM medium. Cellular viability was assessed using MTT assay in three time intervals (24, 48, and 72 h after mixing). Differences in mean cell viability values between materials were assessed by using the One-way ANOVA and Bonferoni post-test. Optical microscopic analysis of morphology of the untreated control and the cement-treated cell cultures were carried out in all experimental periods. Results: It was indicated that there was not a significant difference in cytotoxicity among the materials of test and between them and the control group. However, there was a statistically significant difference between different time intervals within each group (P< 0.05) and between different concentration of test materials (P<0.05). In all samples, set materials showed better viability than fresh ones. Conclusion: According to results of this study, NEC and MTA have similar cytotoxic effect on L929 cell culture. PMID:24171015

  11. Antimicrobial and cytotoxic effects of phosphoric acid solution compared to other root canal irrigants.

    Science.gov (United States)

    Prado, Maíra; Silva, Emmanuel João Nogueira Leal da; Duque, Thais Mageste; Zaia, Alexandre Augusto; Ferraz, Caio Cezar Randi; Almeida, José Flávio Affonso de; Gomes, Brenda Paula Figueiredo de Almeida

    2015-01-01

    Phosphoric acid has been suggested as an irrigant due to its effectiveness in removing the smear layer. The purpose of this study was to compare the antimicrobial and cytotoxic effects of a 37% phosphoric acid solution to other irrigants commonly used in endodontics. The substances 37% phosphoric acid, 17% EDTA, 10% citric acid, 2% chlorhexidine (solution and gel), and 5.25% NaOCl were evaluated. The antimicrobial activity was tested against Candida albicans, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Actinomyces meyeri, Parvimonas micra, Porphyromonas gingivalis, and Prevotella nigrescens according to the agar diffusion method. The cytotoxicity of the irrigants was determined by using the MTT assay. Phosphoric acid presented higher antimicrobial activity compared to the other tested irrigants. With regard to the cell viability, this solution showed results similar to those with 5.25% NaOCl and 2% chlorhexidine (gel and solution), whereas 17% EDTA and 10% citric acid showed higher cell viability compared to other irrigants. Phosphoric acid demonstrated higher antimicrobial activity and cytotoxicity similar to that of 5.25% NaOCl and 2% chlorhexidine (gel and solution).

  12. Cytotoxic Effects of Alcoholic Extract of Dorema Glabrum Seed on Cancerous Cells Viability

    Directory of Open Access Journals (Sweden)

    Maryam Bannazadeh Amirkhiz

    2013-08-01

    Full Text Available Purpose: In the present study cytotoxic effects of the alcoholic extract of Dorema Glabrum seed on viability of WEHI-164 cells, mouse Fibrosarcoma cell line and L929 normal cells were compared with the cytotoxic effects of Taxol (anticancer and apoptosis inducer drug. Methods: To find out the plant extract cytotoxic effects, MTT test and DNA fragmentation assay, the biochemical hallmark of apoptosis were performed on cultured and treated cells. Results: According to the findings the alcoholic extract of Dorema Glabrum seed can alter cells morphology and because of chromatin condensation and other changes they shrink and take a spherical shape, and lose their attachment too. So the plant extract inhibits cell growth albeit in a time and dose dependent manner and results in degradation of chromosomal DNA. Conclusion: Our data well established the anti-proliferative effect of methanolic extract of Dorema Glabrum seed and clearly showed that the plant extract can induce apoptosis and not necrosis in vitro, but the mechanism of its activities remained unknown. These results demonstrated that Dorema Glabrum seed might be a novel and attractive therapeutic candidate for tumor treatment in clinical practices.

  13. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

    Science.gov (United States)

    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.

  14. Cytotoxicity Test of One-Step Self-Etching Bonding Agents by Standardized Dentin Barrier Test Using Polyurethane Discs

    Directory of Open Access Journals (Sweden)

    Mi-Joo Kim

    2013-12-01

    Full Text Available This study was performed to standardize a dentin barrier test with the substitute and evaluate the cytotoxicity of one-step self-etching bonding agents. Each of the natural bovine dentin and polyurethane discs were 500-μm thick and were tested using a perfusion device. Following the treatment with 0.05% phenol on the natural bovine disc or three kinds of polyurethane discs—30, 40, and 50 pcf (pounds per cubic foot—cell viability of L-929 was measured by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and expressed as percentages of non-treated group, respectively. A substitute showing permeability similar to that of bovine dentin was determined based on this result. Cytotoxicity test of bonding agents was performed by the selected substitute, the results of which were expressed as percentages of the control. In addition, SEM images were taken after the tests. The cell viability by 40-pcf polyurethane disc was not statistically different from that by bovine dentin disc (P > 0.05. Futurabond DC resulted in the highest cell viability and Bond force the lowest by the 40-pcf polyurethane disc (P < 0.05. The adhesives on the 40-pcf polyurethane disc changed cellular morphology with different degrees on the SEM images. This standardized test might be useful for assessing the cytotoxicity of dental materials applied to dentin before clinical applications.

  15. Cytotoxic Effect of Turkish Propolis on Liver, Colon, Breast, Cervix ...

    African Journals Online (AJOL)

    Purpose: To investigate the total polyphenolic and flavonoid contents, antioxidant power and cytotoxic activity of ethanol extracts of Turkish propolis (EEP). Methods: The total polyphenolic and flavonoid contents of EEP were determined by spectrometric methods. Antioxidant power and cytotoxic activity of EEP were ...

  16. Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

    National Research Council Canada - National Science Library

    Gao1, Radharaman Ray2, Yan Xiao3, Peter E. Barker3 and Prab, Xiugong

    2006-01-01

    .... In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE...

  17. Physicochemical Characterization and In Vitro Cytotoxic Effect of 3-Hydroxyflavone in a Silver Nanoparticles Complex.

    Science.gov (United States)

    Voicescu, Mariana; Craciunescu, Oana; Moldovan, Lucia; Anastasescu, Mihai; Angelescu, Daniel G; Teodorescu, Valentin S

    2015-09-01

    The aim of this work was to characterize the physico-chemical properties of 3-hydroxyflavone (3-HF) in a silver nanoparticles complex (SNPs) using UV-vis and Fluorescence spectroscopy, Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM) analysis. One also evaluated its effect on the cell viability and morphology of L929 mouse fibroblast cells in vitro. The contribution of the carrier protein, Bovine Serum Albumin (BSA) to 3-HF properties has also been investigated. 3-HF in BSA/SNPs systems presented no cytotoxic effect in L929 mouse fibroblast cells at any of the tested concentrations. The results are discussed with relevance to the oxidative stress process.

  18. Effect of shark cartilage on the cytotoxic activity of NK cells immune system

    Directory of Open Access Journals (Sweden)

    Afshar Bargahi

    2009-12-01

    Full Text Available Background: On the basis of traditional medicine Shark cartilage have been used in the treatment of cancer especially immune related cancers. Then, we hypotheses that shark cartilage contains immune stimulatory ingredients. Methods: The immune stimulatory effect of shark cartilage derived proteins on the cytotoxic activity of natural killer cells(NK cells from healthy human peripheral blood mononuclear cells (hPBMN was studied. Shark cartilage proteins were purified by ion-exchange chromatography and ultra filtration. The effect of each protein fraction on the modulation of cytotoxicity of NK cells, as effectors, against K562, as target cells, was assayed by enzymatic LDH test. Results: The results from cytotoxic assay of NK cells and SDS- Polyacrylamide gell electrophoresis of shark cartilage protein fractions indicated that AR10 fraction, containing proteins with molecular weight of about 14.5 KDa is the most active ingredients of shark cartilage. Conclusion: Shark cartilage contains a 14.5 KDa protein that modulates NK cells activity of human immune system.

  19. Combined cytotoxic effects of pesticide mixtures present in the Chinese diet on human hepatocarcinoma cell line.

    Science.gov (United States)

    Ma, Mengmeng; Chen, Chen; Yang, Guiling; Li, Yun; Chen, Zhijun; Qian, Yongzhong

    2016-09-01

    Consumers might be simultaneously exposed to several pesticide residues contained in their food. Based on the results of previous studies, 20 pesticides were selected due to their high exposure levels to which the Chinese population is likely exposed through the diet. The purpose of this study was to measure the cytotoxicity of these pesticides in HepG2 cells in vitro, as an alternative approach to assess the toxicity of chemicals. Then, the pesticides and some of the mixtures with comparatively high cell-proliferating inhibitory activities were selected to test the cellular ROS level and apoptosis-related protein Caspase-3/7 content in HepG2 cells. The combined effects of these pesticide mixtures with the prediction was based on a combination index (CI)-isobologram equation and the pesticide combinations exhibited various types of interactions (synergism, antagonism, and additivity). Two individuals, one binary combinations, and three uniform design (UD) mixtures of the pesticides were found to have significant cytotoxic effects, along with significant time- and dose-dependent induction of caspase-3/7 activity in vitro, indicating that cytotoxicity caused by these pesticides might be attributed to the pro-oxidative and apoptosis induced potential. Copyright © 2016. Published by Elsevier Ltd.

  20. The cytotoxic effect of Elephantopus scaber Linn extract against breast cancer (T47D) cells

    Science.gov (United States)

    Sulistyani, N.; Nurkhasanah

    2017-11-01

    Breast cancer is one of the main cause of death. Elephantopus scaber Linn (ES) which has been used as a traditional medicine contains an antitumor compounds. This study aimed to explore the active fraction from ethanolic extract of ES as anticancer and to determine its inhibition effect on the cell proliferation cycle of breast cancer (T47D) cells. The ES leaf was macerated with ethanol and then evaporated to get the concentrated extract. The extract was fractionated using petroleum ether, chloroform, and methanol respectively. The cytotoxic activity of each fraction was carried out with MTT method, and the inhibition of cell cycle test were observed by flowcytometry method. The result showed that ES and the fractions have cytotoxic activity against T47D cell lines with IC50 values of extract, petroleum ether, chloroform, and methanol fractions were 58.36±2.38, 132.17±9.69, 7.08±2.11, and 572.89±69.23 µg/mL. The inhibition effect of ethanol extract on the lifecycle of cells was occured in sub G1 phase. There was no prolonging of G1, S, G2/M and polyploidy phase of T47D cell lines. The chloroform fraction of ES is the most cytotoxic fraction against T47D cells without prolonging the cell lifecycle.

  1. Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells.

    Directory of Open Access Journals (Sweden)

    Babli Halder

    Full Text Available In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells.

  2. Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells.

    Science.gov (United States)

    Halder, Babli; Singh, Shruti; Thakur, Suman S

    2015-01-01

    In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells.

  3. Preliminary phytochemical analysis, Antioxidant and cytotoxicity test of Carissa edulis Vahl dried fruits

    Science.gov (United States)

    Fowsiya, J.; Madhumitha, G.

    2017-11-01

    Plants are the main source of medicine which is used in traditional as well as modern medicine in recent years for curing many diseases. Carissa edulis Vahl is one of the traditional plants which have healing property on diarrhea, toothache and chest pain. The present work aims on phytochemical, antioxidant and in vitro cytotoxicity test of C. edulis dried fruits. The different solvent extracts obtained from petroleum ether, ethyl acetate, chloroform, ethanol and water have been evaluated the presence of phytochemicals. Several assays were carried out like total antioxidant, DPPH, reducing power and thiobarbituric acid to investigate the free radical scavenging property. In addition, the cytotoxicity study also carried out on human lung cancer cells (A549). Among different solvent extract, ethanol exhibited strong antioxidant activity. Additionally, the in vitro cytotoxicity test of C. edulis on human lung cancer cell (A549) showed IC50 value 405.704 ± 2.42 μg/mL. Therefore, C. edulis could be useful as a potential preventive intervention for free radicals mediated diseases as well as an antioxidant drug in the pharmaceutical industry.

  4. Cytotoxicity of current adhesive systems: in vitro testing on cell cultures of primary murine macrophages.

    Science.gov (United States)

    Porto, Isabel C C M; Oliveira, Danielle C; Raele, Renata A; Ribas, Ketlin H S; Montes, Marcos A J R; De Castro, Célia M M B

    2011-03-01

    The aim of this study was to evaluate, in vitro, the potential cytotoxicity of dentinal adhesives on alveolar macrophages of Wistar rats, after diffusion through dentin. The cytotoxicity of adhesives [single bond plus (SB), clearfil SE bond (CF) and Xeno V (XE)] applied to the occlusal surface of human dentin disks adapted to a dentin barrier test device were analyzed. The sets placed on a monolayer of cells were incubated for 24, 48 and 72h. Culture medium and Escherichia coli lipopolysaccharides (LPS) were used as negative and positive controls, respectively. Cellular cytotoxicity was evaluated by observing the cell survival rate (MTT assay) and nitric oxide production (NO). The data were analyzed by one-way factorial ANOVA and Tukey's and Tamhane's paired comparisons T2 (α=0.05). All the adhesive systems reduced the percentage of live cells by over 50%, compared with the control group. Within the same period of time, there was a statistically significant difference between the adhesives and LPS compared with the negative control group. SB presented a statistically significant difference between 24h and 72h, and XE between 48h and 72h. The quantity of NO produced in 24h did not differ statistically between the NC and adhesive groups. After 48h there was a significant difference between SB/CF and XE/NC. At 72h only CF showed a significant difference from each of the other groups. LPS differed statistically from all the other groups at all the evaluation times. Components of the adhesives tested may permeate the dentin in sufficient concentrations to cause death and damage to cell metabolism in the alveolar macrophages of rats, which indicates potential cytotoxicity to pulpal cells. Copyright © 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  5. Effect of drug precursor in cell uptake and cytotoxicity of redox-responsive camptothecin nanomedicines.

    Science.gov (United States)

    Botella, Pablo; Muniesa, Carlos; Vicente, Víctor; Cabrera-García, Alejandro

    2016-01-01

    Novel redox-responsive nanomedicines have been synthesized by conjugating camptothecin prodrugs ((pyridine-2-yldisulfanil)alkyl carbonate derivatives) to hybrid porous silica nanoparticles through disulfide bond. After disulfide reduction, camptothecin may be released by an intramolecular cyclization mechanism or by carbonate bond hydrolysis. Samples have been characterized by physico-chemical techniques, and stability and drug release in PBS and human serum have been determined. Moreover, cell uptake was studied by fluorescence microscopy and flow cytometry, whilst cytotoxic activity was validated by MTT test. Obtained results indicate that prodrug side chain carbon number (n=1,2,3) determines material hydrophobic properties and, as a consequence, its stability in aqueous medium. When n value increases, the negative surface charge decreases dramatically due to a shielding effect provoked by hydrophobic ligands, which promotes particle aggregation and favors cell internalization. Furthermore, the n value determines the type of products released and, subsequently, the cytotoxic activity. Full disulfide bridge reduction takes place in all cases, but quick delivery of the free drug by intramolecular cyclization is only possible with the shortest linker (n=1), whereas other nanomedicines only present slow discharge of camptothecin by carbonate hydrolysis. Overall, the drug precursor incorporated to the inorganic nanoplatform modulates both cell uptake rate and cytotoxicity according to the different functionalization. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Cytotoxicity test of 40, 50 and 60% citric acid as dentin conditioner by using MTT assay on culture cell line

    Directory of Open Access Journals (Sweden)

    Christian Khoswanto

    2008-09-01

    Full Text Available Background: Open dentin is always covered by smear layer, therefore before restoration is performed, cavity or tooth which has been prepared should be clean from dirt. The researchers suggested that clean dentin surface would reach effective adhesion between resin and tooth structure, therefore dentin conditioner like citric acid was used to reach the condition. Even though citric acid is not strong acid but it can be very erosive to oral mucous. Several requirements should be fulfilled for dental product such as non toxic, non irritant, biocompatible and should not have negative effect against local, systemic or biological environment. Cytotoxicity test was apart of biomaterial evaluation and needed for standard screening. Purpose: This study was to know the cytotoxicity of 40, 50, 60% citric acid as dentin conditioner using MTT assay. Method: This study is an experimental research using the Post-Test Only Control Group Design. Six samples of each 40, 50 and 60% citric acid for citotoxicity test using MTT assay. The density of optic formazan indicated the number of living cells. All data were statistically analyzed by one way ANOVA. Result: The percentage of living cells in 40, 50 and 60% citric acid were 95.14%, 93.42% and 93.14%. Conclusion: Citric acid is non toxic and safe to be used as dentine conditioner.

  7. Differential cytotoxic effects of Annona squamosa seed extracts on ...

    Indian Academy of Sciences (India)

    /fulltext/jbsc/030/02/0237-0244. Keywords. Annona squamosa seed; cytotoxicity; GSH; ROS; tumour cells. Abstract. Annonaceous acetogenins are a new class of compounds that have been reported to have potent pesticidal, parasiticidal, ...

  8. Cytotoxic effect of TDZ on human cervical cancer cells.

    Science.gov (United States)

    Enkhtaivan, Gansukh; Kim, Doo Hwan; Pandurangan, Muthuraman

    2017-08-01

    The present study investigates the anticancer activity of Thidiazuron (TDZ). Anticancer activity of TDZ was evaluated in cervical carcinoma cells (HeLa cells). Sulforhodamine-B (SRB) assay indicates that TDZ was about 100 times more toxic to the cancer cell than normal cells. TUNEL assay showed TDZ induced DNA damage in tumor cells. The loss of mitochondrial membrane potential (MMP) in cancer cells was observed following TDZ treatment. The Bax and bcl-2 gene expression ratio are highly responsible for the regulation of MMP balance, and these ratio was significantly altered following TDZ treatment. The p53 and caspase-3 expressions were increased in cancer cells following treatment. Caspase-3 activation is the key factor for apoptosis. Cytotoxicity of TDZ on HeLa cells was 100 times higher than normal kidney cell (MDCK cells). Moreover, the anticancer activity of TDZ was tested by DNA damage, mitochondrial dysfunction, some gene expression and caspase-3 inhibition in silico. TDZ detected has higher ability on early apoptosis of cancer cell through DNA damage. Additionally, cancer cellular MMP was significantly reduced under inoculation of TDZ. In silico assay confirmed that TDZ was able to bind with the active site of the capase-3 protein. Therefore, taking all these data together it is suggested that the TDZ may be a potential agent to act against cervical cancer cells. Copyright © 2017. Published by Elsevier B.V.

  9. Anti-inflammatory, anti-cholinergic and cytotoxic effects of Sida rhombifolia.

    Science.gov (United States)

    Mah, Siau Hui; Teh, Soek Sin; Ee, Gwendoline Cheng Lian

    2017-12-01

    Sida (Malvaceae) has been used as a traditional remedy for the treatment of diarrhoea, malarial, gastrointestinal dysentery, fevers, asthma and inflammation. This study evaluates the anti-inflammatory, cytotoxic and anti-cholinergic activities of Sida rhombifolia Linn. whole plant for the first time. S. rhombifolia whole plant was extracted by n-hexane, ethyl acetate and methanol using Soxhlet apparatus. The plant extracts were evaluated for their antioxidant (DPPH, FIC and FRAP), anti-inflammatory (NO and protein denaturation inhibitions), cytotoxic (MTT) and anti-cholinesterase (AChE) properties in a range of concentrations to obtain IC50 values. GC-MS analysis was carried out on the n-hexane extract. The ethyl acetate extract exhibited the most significant antioxidant activities by scavenging DPPH radicals and ferrous ions with EC50 of 380.5 and 263.4 μg/mL, respectively. In contrast, the n-hexane extract showed the strongest anti-inflammatory activity with IC50 of 52.16 and 146.03 μg/mL for NO and protein denaturation inhibition assays, respectively. The same extract also revealed the strongest effects in anti-cholinesterase and cytotoxic tests at the concentration of 100 μg/mL, AChE enzyme inhibition was 58.55% and human cancer cells, SNU-1 and Hep G2 inhibition was 68.52% and 47.82%, respectively. The phytochemicals present in the n-hexane extract are palmitic acid, linoleic acid and γ-sitosterol. The present study revealed that the n-hexane extract possessed relatively high pharmacological activities in anti-inflammation, cytotoxicity and anti-cholinesterase assays. Thus, further work on the detail mechanism of the bioactive phytochemicals which contribute to the biological properties are strongly recommended.

  10. CYTOTOXIC EFFECTS OF ALKYLPHOSPHOCHOLINES OR ALKYLPHOSPHOCHOLINE-LIPOSOMES AND MACROPHAGES ON TUMOR-CELLS

    NARCIS (Netherlands)

    ZEISIG, R; JUNGMANN, S; FICHTNER, [No Value; DAEMEN, T; ARNDT, D

    1994-01-01

    The influence of the alkylphosphocholines (APC) on macrophage activation to tumor cytotoxicity was investigated in vitro with both mouse peritoneal and rat liver macrophages. For this purpose the compouds were used either in micellar or in liposomal form. The cytotoxic effect of micellar or

  11. Digital holographic microscopy overcomes the limitations of in vitro nanomaterial cytotoxicity testing

    Science.gov (United States)

    Mues, Sarah; Ketelhut, Steffi; Kemper, Björn; Schnekenburger, Jürgen

    2017-02-01

    The cytotoxic potential of nanomaterials is commonly evaluated by different cellular endpoints as reactive oxygen species formation, cell viability or cell death. Usually these parameters are determined by intensity based optical readouts that are often influenced by nanomaterial-based interferences. Here we present Digital Holographic Microscopy (DHM) as a multimodal optical method, which overcomes the limitations of conventional in vitro assays based on color or fluorescence read outs. Using cell viability WST8- and cell death LDH-assay we investigated the toxic effects of two representative silver nanomaterials. Therefore, we used a matrix of four cell lines representing different organ functions. Compared to conventional toxicity assays DHM allows time resolved proliferation monitoring which is free of assay system interactions. Also, information about time-dependent mechanisms can be obtained. Additionally, we have analyzed single macrophages for refractive index, cell volume and dry mass after the incubation to cytotoxic silver spheres. The refractive index decreased dose dependent, while cell volume and dry mass stayed constant. We therefore suggest the evaluation of these parameters in cytotoxicity assessment for further evaluation of their relevance under the applied conditions. This demonstrates DHM as valuable label-free tool for nanomaterial toxicity analysis.

  12. Cytotoxic effect of artocarpin on T47D cells.

    Science.gov (United States)

    Arung, Enos Tangke; Wicaksono, Britanto Dani; Handoko, Yohana Ayupriyanti; Kusuma, Irawan Wijaya; Shimizu, Kuniyoshi; Yulia, Dina; Sandra, Ferry

    2010-10-01

    In our screening projects for anticancer agents from natural resources, artocarpin [6-(3-methyl-1-butenyl)-5,2',4'-trihydroxy-3-isoprenyl-7-methoxyflavone] isolated from wood of jack fruit (Artocarpus heterophyllus) showed potent cytotoxic activity on human T47D breast cancer cells. The mode of action of artocarpin was evaluated by its effect on cell viability, nuclear morphology, cell cycle progression, expression of protein markers for apoptosis, and mitochondrial membrane potential (Delta psi m). These results showed that artocarpin caused a reduction of cell viability in a concentration-dependent manner and an alteration of cell and nuclear morphology. Moreover, the percentage of the sub-G1 phase formation was elevated dose-dependently. Artocarpin induced activation of caspase 8 and 10 as indicated by stronger signal intensity of cleaved-caspase 8 and weaker signal intensity of caspase 10 markers detected after artocarpin treatment. In addition, we also noticed the activation of caspase 3 by artocarpin. There were negligible changes in mitochondrial membrane potential (Delta psi m) due to artocarpin treatment. All together, these data indicated that artocarpin induced apoptosis in T47D cells possibly via an extrinsic pathway.

  13. Phosphonium Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines.

    Science.gov (United States)

    Dhanya, Dhanyalayam; Palma, Giuseppe; Cappello, AnnaRita; Mariconda, Annaluisa; Sinicropi, Maria Stefania; Giordano, Francesca; Vecchio, Vitale Del; Ramunno, Anna; Arra, Claudio; Longo, Pasquale; Saturnino, Carmela

    2017-07-19

    Aims/ Objective: Phosphonium salts are compounds whose structural characteristics enable them to cross the plasma and mitochondrial membrane with ease. Cancer cells have higher plasma membrane potentials than normal cells, phosphonium salts selectively accumulate in the mitochondria of neoplastic cells and inhibit mitochondrial function. In the presente work, we investigate the cytotoxic activity of lipophilic phosphonium salt (11-methoxy11-oxo-undecyl) triphenylphosphonium bromide (MUTP) as well as of two new phosphine oxide salts, 3,3'-(methylphosphoryl) dibenzenaminium chloride (SBAMPO) and 3,3' (phenylphosphoryl) dibenzenaminium chloride (SBAPPO) on the proliferation of breast cancer cell line (MCF-7) and human uterin cervix adenocarcinoma cells (HeLa). We show that only MUTP exhibits antiproliferative effects on both cell lines, without affecting normal breast epithelial cell proliferation. More specifically, we demonstrate that MUTP treatment of breast cancer cells is associated with impaired cell-cycle progression and metabolically induces mitochondrial damage and triggers apoptotic cell death in MCF-7 and HeLa cells. Taken together, these findings suggest that MUTP may be capable of selectively targeting neoplastic cell growth and therefore has potential applications as anticancer agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Cytotoxic effects of curcumin in human retinal pigment epithelial cells.

    Directory of Open Access Journals (Sweden)

    Margrit Hollborn

    Full Text Available BACKGROUND: Curcumin from turmeric is an ingredient in curry powders. Due to its antiinflammatory, antioxidant and anticarcinogenic effects, curcumin is a promising drug for the treatment of cancer and retinal diseases. We investigated whether curcumin alters the viability and physiological properties of human retinal pigment epithelial (RPE cells in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Cellular proliferation was investigated with a bromodeoxy-uridine immunoassay, and chemotaxis was investigated with a Boyden chamber assay. Cell viability was determined by trypan blue exclusion. Apoptosis and necrosis rates were determined with a DNA fragmentation ELISA. Gene expression was determined by real-time PCR, and secretion of VEGF and bFGF was examined with ELISA. The phosphorylation level of proteins was revealed by Western blotting. The proliferation of RPE cells was slightly increased by curcumin at 10 µM and strongly reduced by curcumin above 50 µM. Curcumin at 50 µM increased slightly the chemotaxis of the cells. Curcumin reduced the expression and secretion of VEGF under control conditions and abolished the VEGF secretion induced by PDGF and chemical hypoxia. Whereas low concentrations of curcumin stimulated the expression of bFGF and HGF, high concentrations caused downregulation of both factors. Curcumin decreased dose-dependently the viability of RPE cells via induction of early necrosis (above 10 µM and delayed apoptosis (above 1 µM. The cytotoxic effect of curcumin involved activation of caspase-3 and calpain, intracellular calcium signaling, mitochondrial permeability, oxidative stress, increased phosphorylation of p38 MAPK and decreased phosphorylation of Akt protein. CONCLUSION: It is concluded that curcumin at concentrations described to be effective in the treatment of tumor cells and in inhibiting death of retinal neurons (∼10 µM has adverse effects on RPE cells. It is suggested that, during the intake of curcumin as

  15. Cytotoxic Effects of Environmental Toxins on Human Glial Cells.

    Science.gov (United States)

    D'Mello, Fiona; Braidy, Nady; Marçal, Helder; Guillemin, Gilles; Rossi, Fanny; Chinian, Mirielle; Laurent, Dominique; Teo, Charles; Neilan, Brett A

    2017-02-01

    Toxins produced by cyanobacteria and dinoflagellates have increasingly become a public health concern due to their degenerative effects on mammalian tissue and cells. In particular, emerging evidence has called attention to the neurodegenerative effects of the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA). Other toxins such as the neurotoxins saxitoxin and ciguatoxin, as well as the hepatotoxic microcystin, have been previously shown to have a range of effects upon the nervous system. However, the capacity of these toxins to cause neurodegeneration in human cells has not, to our knowledge, been previously investigated. This study aimed to examine the cytotoxic effects of BMAA, microcystin-LR (MC-LR), saxitoxin (STX) and ciguatoxin (CTX-1B) on primary adult human astrocytes. We also demonstrated that α-lipoate attenuated MC-LR toxicity in primary astrocytes and characterised changes in gene expression which could potentially be caused by these toxins in primary astrocytes. Herein, we are the first to show that all of these toxins are capable of causing physiological changes consistent with neurodegeneration in glial cells, via oxidative stress and excitotoxicity, leading to a reduction in cell proliferation culminating in cell death. In addition, MC-LR toxicity was reduced significantly in astrocytes-treated α-lipoic acid. While there were no significant changes in gene expression, many of the probes that were altered were associated with neurodegenerative disease pathogenesis. Overall, this is important in advancing our current understanding of the mechanism of toxicity of MC-LR on human brain function in vitro, particularly in the context of neurodegeneration.

  16. PDMS/glass microfluidic cell culture system for cytotoxicity tests and cells passage

    DEFF Research Database (Denmark)

    Ziolkowska, K.; Jedrych, E.; Kwapiszewski, R.

    2010-01-01

    In this paper, hybrid (PDMS/glass) microfluidic cell culture system (MCCS) integrated with the concentration gradient generator (CGG) is presented. PDMS gas permeability enabled cells' respiration in the fabricated microdevices and excellent glass hydrophilicity allowed successful cells' seeding....... The series of cytotoxicity tests in the microdevice as well as in classic way using 96-well cell culture plates were performed to compare results obtained in micro- and macroscale. Fluorescein dibutyrate (FDB) and iodide propidine (PI) were used as viable and dead cells' markers, respectively. Fabricated...

  17. Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity.

    Science.gov (United States)

    Kośmider, Anita; Czepielewska, Edyta; Kuraś, Mieczysław; Gulewicz, Krzysztof; Pietrzak, Wioleta; Nowak, Renata; Nowicka, Grażyna

    2017-04-12

    Uncaria tomentosa is a woody vine with a long history of use in traditional Peruvian medicine and nowadays supplements containing this vine as ingredient are available. Immunomodulating, anti-inflammatory and anticancer properties of Uncaria tomentosa have been suggested and attributed mainly to the presence of tetracyclic or pentacyclic oxindole alkaloids. However, the synergic action of different compounds occurring in extracts and modulation of redox processes may significantly influence the anticancer activity of Uncaria tomentosa. The aim of the present study was to investigate for the first time the cytotoxic effects of the tetracyclic alkaloids free aqueous extract (decoction) of dried Uncaria tomentosa leaf blades in normal and cancer cells, and to assess the effect of the tested extract on cisplatin (CDDP) cytotoxicity. Tested Uncaria tomentosa extract was not cytotoxic for NHDF cells, but demonstrated cytotoxic effect against HepG2 cells. The extract increased ROS production in HepG2 cells, which resulted in decreased GSH level, leading to apoptosis of these cells through activation of caspase-3 and caspase-7. A reduction of NF-κB active form was observed in cancer cells. In normal cells the extract did not affect ROS production, GSH level and NF-κB activity, and maintained cell viability. HepG2 cells incubation with Uncaria tomentosa decoction and simultaneously with CDDP resulted in an increase in CDPP cytotoxic activity against HepG2, while under the same conditions Uncaria tomentosa prevents NHDF cell viability reduction due to CDDP. The results indicate that Uncaria tomentosa leaves decoction modulates differently cancer and normal cells oxidative metabolism and, enhanced cytotoxicity of CDDP against cancer cells and at the same time increased normal healthy cells resistance to cisplatin. Further studies are needed to confirm our observations and to describe underlying molecular mechanism, and the potential usefulness of Uncaria tomentosa decoction

  18. Evaluation of the genotoxic and cytotoxic effects of crude extracts of Cordia ecalyculata and Echinodorus grandiflorus.

    Science.gov (United States)

    da Silva, Cristiano José; Bastos, Jairo Kenupp; Takahashi, Catarina Satie

    2010-02-03

    Cordia ecalyculata Vell. and Echinodorus grandiflorus (Cham. & Schltdl.) Micheli are extensively used in Brazil as therapeutic preparations for indigenous groups and the general population. These plants have been used in the folk medicine as: tonic, diuretic, anti-inflammatory, appetite suppressants, for the treatment of snake bites, and weight loss. In this study, it was verified the possible cytotoxic and genotoxic effects of the crude extracts of. Cordia ecalyculata and Echinodorus grandiflorus, as well as their effectiveness in treating obesity. The Micronucleus Test was used for the evaluation of possible clastogenic and aneugenic effects, and the Comet Assay was used for the evaluation of single-strand and double-strand DNA breaks. The cytotoxic effects of the crude extracts were verified by PCE/NCE ratio. Swiss mice (Mus musculus) were used as the experimental model. It was observed a significant (PCordia ecalyculata or Echinodorus grandiflorus extracts, in comparison with the negative control. There were no significant differences (P>0.05) in the frequency of micronucleated polychromatic erythrocytes for both extract treatment. We observed that treatment with the Cordia ecalyculata extract at concentrations of 1000 and 2000 mg/kg bw resulted in a PCE/NCE ratio that was larger (P0.05). The results of this study allowed us to infer that the crude extracts of Cordia ecalyculata and Echinodorus grandiflorus do not display cytotoxic or genotoxic activities. However, they do possess weak clastogenic activity (without significance) on peripheral blood cells. Contrary to commonly held beliefs it was also found in this study that the extracts are not effective for obesity treatments. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  19. The in vitro cytotoxicity of eluates from dentin bonding resins and their effect on tyrosine phosphorylation of L929 cells.

    Science.gov (United States)

    Kaga, M; Noda, M; Ferracane, J L; Nakamura, W; Oguchi, H; Sano, H

    2001-07-01

    The aim of this study was to examine the relationship between the monomers eluted from dentin-bonding systems and their cytotoxicities, and to investigate the biochemical effect of the monomers on tyrosine phosphorylation, especially relating to the cell growth activity, of L929 cells in vitro. The primers, uncured or cured adhesives (3M and Kuraray) were tested to determine the cytotoxicity of confluent L929 cells cultured by Eagle's MEM medium supplemented with 10% FCS. The area of cells affected by the eluted monomers were evaluated with an image analyzer and the concentrations of monomers eluted into the medium were measured with high performance liquid chromatography (HPLC) after 24h incubation. The protein composition of the stimulated cells was compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tyrosine phosphorylation was detected by Western blot. The primer and uncured adhesives revealed variable cytotoxicities. 2-hydroxyethyl-methacrylate (HEMA) was the major component eluted from uncured primers and adhesives. Small amounts of triethylene glycol dimethacrylate (TEGDMA) were also detected from the uncured adhesives. The cytotoxicities of the adhesives decreased as photo activation time increased. The amount of monomers eluted from the cured adhesives was almost undetectable and did not reach a sufficient concentration to suppress cell viability or cell growth. The cytotoxicities of the primers and adhesives correlated well with the amounts of either HEMA or TEGDMA eluted. Moreover, a high concentration of HEMA (4 mg/ml medium) affected intracellular tyrosine phosphorylation, which is related to cellular activities. Although the monomers present in dentin bonding resins are cytotoxic to L929 cells, the amount from cured bonding resin is very small and does not provide a cytotoxic dose. This data does however suggest that clinical exposure to the uncured primers and adhesives of dentin bonding resins should be minimized.

  20. Phenolic content, antioxidant effect and cytotoxic activity of Leea indica leaves

    Directory of Open Access Journals (Sweden)

    Reddy Nidyaletchmy

    2012-08-01

    Full Text Available Abstract Background The leaves of Leea indica (Vitaceae, commonly known as ‘Huo Tong Shu’ in Malaysia, have been traditionally used as natural remedy in folk medicine by the locals. The current study reports the outcome of antioxidant and cytotoxic investigation of L. indica leaves. To the best of our knowledge, this is the first report of L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water for evaluation of total phenolic content, antioxidant effect and cytotoxic activity against colon cancer cell lines. Methods In the present study, L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water were firstly prepared prior to phenolic content, antioxidant effect and cytotoxic activity assessment. Folin-Ciocalteau’s method was used for the measurement of total phenolic content of the extracts. The antioxidant activity was measured by employing three different established testing systems, such as scavenging activity on DPPH (1,1-diphenyl-2-picrylhydrazyl radicals, reducing power assay and SOD (superoxide dismutase activity assay. The cytotoxic activity of the extracts were evaluated against three colon cancer cell lines with varying molecular characteristics (HT-29, HCT-15 and HCT-116 by MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] assay. Results The total phenolic content and antioxidant capabilities differed significantly among the L. indica leaf extracts. A strong correlation between total phenolic content and antioxidant properties was found, indicating that phenolic compounds are the major contributor to the antioxidant properties of these extracts. Among the crude ethanol and its fractionated extracts, fractionated water extract showed significantly the highest total phenolic content and strongest antioxidant effect in all the antioxidant testing systems employed in this study. All the four extracts exert no damage to the selected colon cancer

  1. Formation and Biological Targets of Quinones: Cytotoxic versus Cytoprotective Effects.

    Science.gov (United States)

    Bolton, Judy L; Dunlap, Tareisha

    2017-01-17

    Quinones represent a class of toxicological intermediates, which can create a variety of hazardous effects in vivo including, acute cytotoxicity, immunotoxicity, and carcinogenesis. In contrast, quinones can induce cytoprotection through the induction of detoxification enzymes, anti-inflammatory activities, and modification of redox status. The mechanisms by which quinones cause these effects can be quite complex. The various biological targets of quinones depend on their rate and site of formation and their reactivity. Quinones are formed through a variety of mechanisms from simple oxidation of catechols/hydroquinones catalyzed by a variety of oxidative enzymes and metal ions to more complex mechanisms involving initial P450-catalyzed hydroxylation reactions followed by two-electron oxidation. Quinones are Michael acceptors, and modification of cellular processes could occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radical anions leading to the formation of reactive oxygen species (ROS) including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can alter redox balance within cells through the formation of oxidized cellular macromolecules including lipids, proteins, and DNA. This perspective explores the varied biological targets of quinones including GSH, NADPH, protein sulfhydryls [heat shock proteins, P450s, cyclooxygenase-2 (COX-2), glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1, (NQO1), kelch-like ECH-associated protein 1 (Keap1), IκB kinase (IKK), and arylhydrocarbon receptor (AhR)], and DNA. The evidence strongly suggests that the numerous mechanisms of quinone modulations (i.e., alkylation versus oxidative stress) can be correlated with the known pathology/cytoprotection of the parent compound(s) that is best described by an inverse U-shaped dose-response curve.

  2. Cymbopogon citratus essential oil: effect on polymicrobial caries-related biofilm with low cytotoxicity

    Directory of Open Access Journals (Sweden)

    Maria Alcionéia Carvalho de OLIVEIRA

    2017-11-01

    Full Text Available Abstract The objective of this study was to evaluate the effects of Cymbopogon citratus essential oil and its main compound (citral against primary dental colonizers and caries-related species. Chemical characterization of the essential oil was performed by gas chromatography/mass spectroscopy (GC/MS, and the main compound was determined. Antimicrobial activity was tested against Actinomyces naeslundii, Lactobacillus acidophilus, S. gordonii, S. mitis, S. mutans, S. sanguinis and S. sobrinus. Minimum inhibitory and bactericide concentrations were determined by broth microdilution assay for streptococci and lactobacilli reference, and for clinical strains. The effect of the essential oil on bacterial adhesion and biofilm formation/disruption was investigated. Negative (without treatment and positive controls (chlorhexidine were used. The effect of citral on preformed biofilm was also tested using the same methodology. Monospecies and microcosm biofilms were tested. ANOVA or Kruskal-Wallis tests were used (α=0.05. Cytotoxicity of the essential oil to human keratinocytes was performed by MTT assay. GC/MS demonstrated one major component (citral. The essential oil showed an inhibitory effect on all tested bacterial species, including S. mutans and L. acidophilus. Essential oil of C. citratus (10X MIC reduced the number of viable cells of lactobacilli and streptococci biofilms (p < 0.05. The essential oil inhibited adhesion of caries-related polymicrobial biofilm to dental enamel (p < 0.01. Citral significantly reduced the number of viable cells of streptococci biofilm (p < 0.001. The essential oil showed low cytotoxicity to human keratinocytes. Based on these findings, this study can contribute to the development of new formulations for products like mouthwash, against dental biofilms.

  3. Evaluation of antioxidant, antibacterial and cytotoxic effects of green synthesized silver nanoparticles by Piper longum fruit

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, N. Jayachandra; Nagoor Vali, D.; Rani, M.; Rani, S. Sudha, E-mail: sadrassudha@gmail.com

    2014-01-01

    Silver nanoparticles synthesized through bio-green method has been reported to have biomedical applications to control pathogenic microbes as it is cost effective compared to commonly used physical and chemical methods. In present study, silver nanoparticles were synthesized using aqueous Piper longum fruit extract (PLFE) and confirmed by UV–visible spectroscopy. The nanoparticles were spherical in shape with an average particle size of 46 nm as determined by scanning electronic microscopy (SEM) and dynamic light scattering (DLS) particle size analyzer respectively. FT-IR spectrum revealed the capping of the phytoconstituents, probably polyphenols from P. longum fruit extract and stabilizing the nanoparticles. Further the ferric ion reducing test, confirmed that the capping agents were condensed tannins. The aqueous P. longum fruit extract (PLFE) and the green synthesized silver nanoparticles (PLAgNPs) showed powerful antioxidant properties in in vitro antioxidant assays. The results from the antimicrobial assays suggested that green synthesized silver nanoparticles (PLAgNPs) were more potent against pathogenic bacteria than the P. longum fruit extract (PLFE) alone. The nanoparticles also showed potent cytotoxic effect against MCF-7 breast cancer cell lines with an IC 50 value of 67 μg/ml/24 h by the MTT assay. These results support the advantages of using bio-green method for synthesizing silver nanoparticles with antioxidant, antimicrobial and cytotoxic activities those are simple and cost effective as well. - Highlights: • 46 nm spherical shaped P. longum fruit silver nanoparticles was prepared. • Capping and reducing bioactive plant compounds with in nanoparticles were condensed tannins. • Particles are potent antioxidant and anti microbial in biological systems. • They are cytotoxic against MCF-7 cell lines.

  4. Anti-inflammatory, cytotoxic and antioxidant effects of methanolic ...

    African Journals Online (AJOL)

    The aim of this study was to investigate in vitro antioxidant, anti-inflammatory and cytotoxic activities of the petroleum ether, ethyl acetate, methanol and aqueous extracts obtained from leaves of Drypetes sepiaria (Euphorbiaceae). Total phenolic and flavonoid contents of these crude extracts were determined as gallic acid ...

  5. Cytotoxic effect of betulinic acid and betulinic acid acetate isolated ...

    African Journals Online (AJOL)

    GREGORY

    2010-09-20

    Sep 20, 2010 ... Key words: Betulinic acid, HL 60, cytotoxicity, MTT assay, DNA laddering, Cell cycle PI. INTRODUCTION. Betulinic acid ... Chemical structure of betulinic acid and its derivatives. (Fulda et al., 1999) and leukemia cells ... feature makes betulinic acid unique in comparison to compounds that are currently used ...

  6. Antipyretic, analgesic, anti-inflammatory and cytotoxic effects of four ...

    African Journals Online (AJOL)

    ... and 2-acetamido-5-sulfonamidobenzoic acid (AMSABA, 4) were synthesized and evaluated for their analgesic, antipyretic, anti-inflammatory and cytotoxic activities. HASBA, AASBA and AMASBA showed higher analgesic activity than aspirin (ASA) at 100 mg/kg dose, while AMSABA showed the least analgesic property.

  7. Effects of the Absorption Behaviour of ZnO Nanoparticles on Cytotoxicity Measurements

    Directory of Open Access Journals (Sweden)

    Nigar Najim

    2014-01-01

    Full Text Available ZnO absorbs certain wavelengths of light and this behavior is more pronounced for nanoparticles of ZnO. As many toxicity measurements rely on measuring light transmission in cell lines, it is essential to determine how far this light absorption influences experimental toxicity measurements. The main objective was to study the ZnO absorption and how this influenced the cytotoxicity measurements. The cytotoxicity of differently sized ZnO nanoparticles in normal and cancer cell lines derived from lung tissue (Hs888Lu, neuron-phenotypic cells (SH-SY5Y, neuroblastoma (SH-SY5Y, human histiocytic lymphoma (U937, and lung cancer (A549 was investigated. Our results demonstrate that the presence of ZnO affected the cytotoxicity measurements due to the absorption characteristic of ZnO nanoparticles. The data revealed that the ZnO nanoparticles with an average particle size of around 85.7 nm and 190 nm showed cytotoxicity towards U937, SH-SY5Y, differentiated SH-SY5Y, and Hs888Lu cell lines. No effect on the A549 cells was observed. It was also found that the cytotoxicity of ZnO was particle size, concentration, and time dependent. These studies are the first to quantify the influence of ZnO nanoparticles on cytotoxicity assays. Corrections for absorption effects were carried out which gave an accurate estimation of the concentrations that produce the cytotoxic effects.

  8. Single and combined genotoxic and cytotoxic effects of two xenobiotics widely used in intensive aquaculture.

    Science.gov (United States)

    Jerbi, Mohamed Ali; Ouanes, Zouhour; Besbes, Raouf; Achour, Lotfi; Kacem, Adnen

    2011-09-18

    Several chemicals are used in aquaculture to prevent or to treat disease outbreaks. These substances are mainly administered by two different routes: by prolonged immersion or by mixing into the diet. In the case of intensive aquaculture, the chemicals that are most frequently applied by immersion are formaldehyde (FA) 37% and oxytetracycline (OTC). The first is highly effective against most protozoa, as well as some of the most common parasites such as monogenetic trematodes. OTC presents a large spectrum of antibacterial activities and is used to treat systemic bacterial infections that affect fish. Under therapeutic use, FA (37%) is applied prophylactically at 200ml/m(3), whereas OTC is used curatively at 40g/m(3). The goal of the present study is to assess genotoxic and cytotoxic effects associated with exposure of the European sea bass (Dicentrarchus labrax) to FA37% and OTC under the same conditions as those applied in intensive aquaculture systems. To this end the micronucleus (MN) assay was applied in erythrocytes. Our results show that both tested chemicals present genotoxic and cytotoxic potential following a time-dependent pattern. Remarkably, the combined treatment induces a cumulative effect, which is particularly pronounced after 15 days of exposure. This suggests the critical hazards associated with exposure to FA and OTC when applied or released together. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes.

    Science.gov (United States)

    Raiola, Assunta; Del Giudice, Rita; Monti, Daria Maria; Tenore, Gian Carlo; Barone, Amalia; Rigano, Maria Manuela

    2015-12-25

    Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid) decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods.

  10. Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes

    Directory of Open Access Journals (Sweden)

    Assunta Raiola

    2015-12-01

    Full Text Available Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods.

  11. Cytotoxicity of cis-platinum(II) conjugate models. The effect of chelating arms and leaving groups on cytotoxicity: a quantitative structure-activity relationship approach.

    Science.gov (United States)

    Monti, Elena; Gariboldi, Marzia; Maiocchi, Alessandro; Marengo, Emilio; Cassino, Claudio; Gabano, Elisabetta; Osella, Domenico

    2005-02-10

    Thirteen newly synthesized or resynthesized diamine-platinum(II) complexes were characterized, and their cytotoxic activities (IC50) were tested on parental and resistant ovarian cancer cell lines. They represent models of conjugates between biologically active vectors and cytotoxic Pt(II) moieties within the "drug targeting and delivery strategy". Three drugs, routinely employed in the clinical treatment of cancer, namely, cisplatin, carboplatin, and oxaliplatin, were also included in the study as controls. The quantitative structure-activity relationship approach provides simple regression models able to predict log(1/IC50) of diamine-platinum(II) complexes on both parental and resistant ovarian cancer cell lines. The 16 complexes were characterized using 197 molecular descriptors, after which the best regression models relating a subset of these descriptors to the log(1/IC50) in the two cancer cell lines were calculated. Models with four variables proved to be endowed with very good predictive ability Q2(LMO-50%) > or = 85.6%, making it possible to discard 50% of the molecules from the test set following for cross-validation procedure. A four-variable regression model also proved effective in predicting the resistance index RI, Q2(LMO-50%) = 84.4%.

  12. Kelussia odoratissima potentiates cytotoxic effects of radiation in HeLa cancer cell line

    Directory of Open Access Journals (Sweden)

    Azar Hosseini

    2017-02-01

    Full Text Available Objective: Cervical cancer is the second most common cause of death from cancer in women throughout the world. The aim of this study was to evaluate the cytotoxic activity of Kelussia odoratissima (K. odoratissima extract associated with radiotherapy in cervical cancer cells (HeLa cell line.Materials and Methods: Different concentration of the extract (25-500µg/ml was tested in HeLa cell lines. Cell cytotoxicity of the extract and the effects of the extract on radiation (2Gy/min-induced damages were assessed by MTT assay. Apoptosis was assessed using flow cytometric analysis.Result: K. odoratissima decreased cell viability in HeLa cell line in a concentration and time-dependent manner. When compared to the control,K. odoratissima induced a sub-G1 peak in the flow cytometry histogram of treated cells, indicating that apoptotic cell death is involved in K. odoratissima-induced toxicity. It was also shown that K. odoratissima sensitizes cells to radiation-induced toxicity.Conclusion: Our result showed the extract increased the radiation effect. This observation may be related to the presence of active compounds such as phthalides and ferulic acid.

  13. Antischistosomal and Cytotoxic Effects of the Essential Oil of Tetradenia riparia (Lamiaceae).

    Science.gov (United States)

    de Melo, Nathalya I; Mantovani, André L L; de Oliveira, Pollyanna F; Groppo, Milton; Filho, Ademar A Da Silva; Rodrigues, Vanderlei; Cunha, Wilson R; Tavares, Denise C; Magalhães, Lizandra G; Crottii, Antônio E M

    2015-09-01

    This paper reports on the antischistosomal and cytotoxic effects of the essential oil obtained from Tetradenia riparia leaves (TR-EO). At concentrations of 50 and 100 µg/mL, TR-EO killed all the worms after 120 and 24 h of incubation, respectively. At a concentration equal to or higher than 50 µg/mL, this oil also separated the coupled pairs and decreased the adult worm motor activity after incubation periods higher than 72 h. In addition, at 120 h of incubation, TR-EO slightly decreased the number of eggs produced by Schistosoma mansoni adult worms and significantly reduced the percentage of developed eggs, in a dose-dependent manner. XTT-colorimetric assays showed that the tested TR-EO concentrations were not considerably cytotoxic to V79 cells (IC50 = 253.5 µg/mL). The effects of TR-EO on egg development were noteworthy; therefore, this essential oil deserves further investigation to identify the chemical constituents that elicit activity against S. mansoni.

  14. Novel magnesium alloy Mg–2La caused no cytotoxic effects on cells in physiological conditions

    Energy Technology Data Exchange (ETDEWEB)

    Weizbauer, Andreas, E-mail: weizbauer.andreas@mh-hannover.de [Laboratory for Biomechanics and Biomaterials, Department of Orthopedic Surgery, Hannover Medical School, Anna-von-Borries-Straße 1-7, 30625 Hannover (Germany); CrossBIT, Center for Biocompatibility and Implant-Immunology, Department of Orthopedic Surgery, Hannover Medical School, Feodor-Lynen-Str. 31, 30625 Hannover (Germany); Seitz, Jan-Marten [Institute of Materials Science, Leibniz Universität Hannover, An der Universität 2, 30823 Garbsen (Germany); Werle, Peter [ABB AG, Trafoweg 4, 06112 Halle (Germany); Hegermann, Jan [Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover (Germany); Willbold, Elmar [Laboratory for Biomechanics and Biomaterials, Department of Orthopedic Surgery, Hannover Medical School, Anna-von-Borries-Straße 1-7, 30625 Hannover (Germany); CrossBIT, Center for Biocompatibility and Implant-Immunology, Department of Orthopedic Surgery, Hannover Medical School, Feodor-Lynen-Str. 31, 30625 Hannover (Germany); Eifler, Rainer [Institute of Materials Science, Leibniz Universität Hannover, An der Universität 2, 30823 Garbsen (Germany); Windhagen, Henning [Laboratory for Biomechanics and Biomaterials, Department of Orthopedic Surgery, Hannover Medical School, Anna-von-Borries-Straße 1-7, 30625 Hannover (Germany); Reifenrath, Janin [Small Animal Clinic, University of Veterinary Medicine Hannover, Bünteweg 9, 30559 Hannover (Germany); Waizy, Hazibullah [Laboratory for Biomechanics and Biomaterials, Department of Orthopedic Surgery, Hannover Medical School, Anna-von-Borries-Straße 1-7, 30625 Hannover (Germany)

    2014-08-01

    Using several different in vitro assays, a new biodegradable magnesium alloy Mg–2La, composed of 98% magnesium and 2% lanthanum, was investigated as a possible implant material for biomedical applications. An in vitro cytotoxicity test, according to EN ISO 10993-5/12, with L929 and human osteoblastic cells identified no toxic effects on cell viability at physiological concentrations (at 50% dilutions and higher). The metabolic activity of human osteoblasts in the 100% extract was decreased to < 70% and was therefore rated as cytotoxic. The degradation rates of Mg–2La were evaluated in phosphate buffered saline and four different cell culture media. The degradation rates were shown to be influenced by the composition of the solution, and the addition of fetal bovine serum slightly accelerated the corrosive process. The results of these in vitro experiments suggest that Mg–2La is a promising candidate for use as an orthopedic implant material. - Highlights: • A new magnesium alloy (Mg–2La) has been developed. • Magnesium alloy Mg–2La revealed no toxic effect in physiological concentrations. • Degradation rates were influenced by the corrosion media. • The addition of fetal bovine serum increased the corrosive process slightly.

  15. Lactobacillus delbrueckii ssp. bulgaricus B-30892 can inhibit cytotoxic effects and adhesion of pathogenic Clostridium difficile to Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Banerjee Pratik

    2009-04-01

    Full Text Available Abstract Background Probiotic microorganisms are receiving increasing interest for use in the prevention, treatment, or dietary management of certain diseases, including antibiotic-associated diarrhea (AAD. Clostridium difficile is the most common cause of AAD and the resulting C. difficile – mediated infection (CDI, is potentially deadly. C. difficile associated diarrhea (CDAD is manifested by severe inflammation and colitis, mostly due to the release of two exotoxins by C. difficile causing destruction of epithelial cells in the intestine. The aim of this study was to determine the effect of probiotic bacteria Lactobacillus delbrueckii ssp. bulgaricus B-30892 (LDB B-30892 on C. difficile-mediated cytotoxicity using Caco-2 cells as a model. Methods Experiments were carried out to test if the cytotoxicity induced by C. difficile-conditioned-medium on Caco-2 cells can be altered by cell-free supernatant (CFS from LDB B-30892 in different dilutions (1:2 to 1:2048. In a similar experimental setup, comparative evaluations of other probiotic strains were made by contrasting the results from these strains with the results from LDB B-30892, specifically the ability to affect C. difficile induced cytotoxicity on Caco-2 monolayers. Adhesion assays followed by quantitative analysis by Giemsa staining were conducted to test if the CFSs from LDB B-30892 and other probiotic test strains have the capability to alter the adhesion of C. difficile to the Caco-2 monolayer. Experiments were also performed to evaluate if LDB B-30892 or its released components have any bactericidal effect on C. difficile. Results and discussion Co-culturing of LDB B-30892 with C. difficile inhibited the C. difficile-mediated cytotoxicity on Caco-2 cells. When CFS from LDB B-30892-C. difficile co-culture was administered (up to a dilution of 1:16 on Caco-2 monolayer, there were no signs of cytotoxicity. When CFS from separately grown LDB B-30892 was mixed with the cell-free toxin

  16. Cymbopogon citratus essential oil: effect on polymicrobial caries-related biofilm with low cytotoxicity.

    Science.gov (United States)

    Oliveira, Maria Alcionéia Carvalho de; Borges, Aline Chiodi; Brighenti, Fernanda Lourenção; Salvador, Marcos José; Gontijo, Aline Vidal Lacerda; Koga-Ito, Cristiane Yumi

    2017-11-06

    The objective of this study was to evaluate the effects of Cymbopogon citratus essential oil and its main compound (citral) against primary dental colonizers and caries-related species. Chemical characterization of the essential oil was performed by gas chromatography/mass spectroscopy (GC/MS), and the main compound was determined. Antimicrobial activity was tested against Actinomyces naeslundii, Lactobacillus acidophilus, S. gordonii, S. mitis, S. mutans, S. sanguinis and S. sobrinus. Minimum inhibitory and bactericide concentrations were determined by broth microdilution assay for streptococci and lactobacilli reference, and for clinical strains. The effect of the essential oil on bacterial adhesion and biofilm formation/disruption was investigated. Negative (without treatment) and positive controls (chlorhexidine) were used. The effect of citral on preformed biofilm was also tested using the same methodology. Monospecies and microcosm biofilms were tested. ANOVA or Kruskal-Wallis tests were used (α=0.05). Cytotoxicity of the essential oil to human keratinocytes was performed by MTT assay. GC/MS demonstrated one major component (citral). The essential oil showed an inhibitory effect on all tested bacterial species, including S. mutans and L. acidophilus. Essential oil of C. citratus (10X MIC) reduced the number of viable cells of lactobacilli and streptococci biofilms (p biofilm to dental enamel (p biofilm (p dental biofilms.

  17. Cytotoxic effect of ICD-85 (venom-derived peptides on MDA-MB-231 cell line

    Directory of Open Access Journals (Sweden)

    A Zare Mirakabadi

    2008-01-01

    Full Text Available Since 1987, when chemopreventive testing programs began, more than 1,000 agents and agent combinations have been selected and evaluated in preclinical studies of chemopreventive activity against various types of cancers. In the present study we aimed to provide quantitative and qualitative characterization of biological and pharmacological activities of ICD-85 on MDA-MB-231 cell line (a highly invasive breast cancer cell line in order to gain a better understanding of the cytotoxic and apoptotic effects of this compound. For this study, the MDA-MB-231 cell line was used and the effect of ICD-85 was assayed by measuring the activity of the cytosolic enzyme lactate dehydrogenase (LDH, released into the culture medium after membrane damage. Morphological alterations of cells were investigated in the control group and cells incubated with ICD-85 as cytotoxic agent. Results showed, in the test group, that cells incubated with 16 µg/mL of ICD-85 had decreased cytoplasmic branching. Some cells were had ruptured and lost the continuity of their surrounding membranes while some had shrunk. Cells incubated with higher doses (above16 µg/mL showed similar changes towards cellular normality with more severity. Results obtained from the ICD-85 stability test reveal that the effect of ICD-85 on MDA-MB-231 cell line in culture medium is stable throughout the incubation time period (24 hours. It appears that ICD-85 at higher concentrations acts at the membrane level, which allows the passage of ions down the concentration gradient, resulting in osmotic changes in organelles followed by several unidentified mechanisms leading to cell death. At lower concentrations, it appears that ICD-85 can prevent cell growth by another mechanism, which may be one of the causes for apoptosis in the cell line.

  18. Effectively enhancing cytotoxic and apoptotic effects of alpha-momorcharin by integrating a heparin-binding peptide.

    Science.gov (United States)

    Tan, Meng-Jie; Cao, Xue-Wei; Li, Peng-Fei; Zhai, Yi-Zhou; Zhou, Yu; Liu, Ye-Jun; Zhao, Jian; Wang, Fu-Jun

    2017-11-01

    Alpha-momorcharin (α-MMC), a type I ribosome-inactivating protein, has attracted a great deal of attention because of its antitumor activity. However, the cytotoxicity of α-MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of α-MMC, a heparin-binding domain derived from heparin-binding epidermal growth factor (named heparin-binding peptide [HBP]) was used as a cell-penetrating peptide and fused to the C-terminus of α-MMC. This novel α-MMC-HBP fusion protein was expressed and purified with a Ni 2+ -resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of α-MMC. HBP was able to efficiently carry α-MMC into the tested cancer cells and significantly enhance the cytotoxic effects of α-MMC in a dose-dependent manner. This enhanced cytotoxic ability occurred due to the higher level of cell apoptosis induced by α-MMC-HBP, which was demonstrated in western blot analysis in which α-MMC-HBP triggered caspase 8, caspase 9, casapase 3, and PARP more intensely than α-MMC alone. α-MMC-HBP led to an upregulation of cleaved PARP and an increase in the Bax/Bcl-2 ratio. Our study provided a new practical way to greatly improve the antitumor activity of α-MMC, which could significantly expand the pharmaceutical applications of α-MMC. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  19. Effects of the Amino Acid Constituents of Microcystin Variants on Cytotoxicity to Primary Cultured Rat Hepatocytes

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    Kumiko Shimizu

    2013-12-01

    Full Text Available Microcystins, which are cyclic heptapeptides produced by some cyanobacterial species from algal blooms, strongly inhibit serine/threonine protein phosphatase and are known as hepatotoxins. Microcystins have many structural variations, yet insufficient information is available on the differences in the cytotoxic potentials among the structural variants. In this study, the cytotoxicities of 16 microcystin variants at concentrations of 0.03–10 μg/mL to primary cultured rat hepatocytes were determined by measuring cellular ATP content, and subsequently determined by their 50% inhibitory concentration (IC50. Differences in the amino acid constituents were associated with differences in cytotoxic potential. [d-Asp3, Z-Dhb7] microcystin-LR exhibited the strongest cytotoxicity at IC50 of 0.053 μg/mL among the microcystin variants tested. Furthermore, [d-Asp3, Z-Dhb7] microcystin-HtyR was also highly cytotoxic. These results suggest that both d-Asp and Z-Dhb residues are important in determining the cytotoxic potential of microcystin variants.

  20. Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity.

    Science.gov (United States)

    García-Muñoz, Ricardo; López-Díaz-de-Cerio, Ascensión; Feliu, Jesus; Panizo, Angel; Giraldo, Pilar; Rodríguez-Calvillo, Mercedes; Grande, Carlos; Pena, Esther; Olave, Mayte; Panizo, Carlos; Inogés, Susana

    2016-04-01

    Follicular lymphoma (FL) is a disease of paradoxes-incurable but with a long natural history. We hypothesized that a combination of lymphokine-activated killer (LAK) cells and monoclonal antibodies might provide a robust synergistic treatment and tested this hypothesis in a phase II clinical trial (NCT01329354). In this trial, in addition to R-CHOP, we alternated the administration of only rituximab with rituximab and autologous LAK cells that were expanded ex vivo. Our objective was to determine the in vitro capability of LAK cells generated from FL patients to produce cytotoxicity against tumor cell lines and to determine rituximab- and obinutuzumab-induced cytotoxicity via antibody-dependent cellular cytotoxicity (ADCC) activity. We analyzed the LAK cell-induced cytotoxicity and rituximab (R)- and obinutuzumab (GA101)-induced ADCC activity. We show that LAK cells generated from FL patients induce cytotoxicity against tumor cell lines. R and GA101 enhance cytolysis through ADCC activity of LAK cells. Impaired LAK cell cytotoxicity and ADCC activity were detected in 50 % of patients. Percentage of NK cells in LAK infusions were correlated with the R- and GA101-induced ADCC. Our results indicate that the combination of R or GA101 and LAK cells should be an option as frontline maintenance therapy in patients with FL.

  1. Cytotoxic effect of some natural compounds isolated from Lauraceae plants and synthetic derivatives.

    Science.gov (United States)

    Cuca, Luis Enrique; Coy, Ericsson David; Alarcón, Marlén Andrea; Fernández, Andrés; Aristizábal, Fabio Ancízar

    2011-01-01

    The antiproliferative effect of eleven neolignans, two lignans and one diterpene isolated from three Lauraceae plants, four benzofurans and two bicyclooctanes synthetic derivatives was evaluated in vitro on a set of five human cancer cells from solid tumors with a high incidence in Colombia. To evaluate the cytotoxic effect of twenty compounds on the tumor cell lines HeLa, A-549, Hep-2, PC-3, and MCF-7. MATERIALS AND METHODS. Fourteen natural compounds were isolated by chromatographic techniques from three native Colombian plants (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), whose structures were established by spectroscopic methods; six synthetic derivatives were prepared by oxyarylation and diazomethane methylation. Antiproliferative effect and cell recovery were performed by means of in vitro treatment of tumor cell lines with test compounds, evaluating cell viability by resazurin staining. Among test compounds, only neolignans ocophyllal A, cinerin D, kaurenoic acid, two benzofuran-derivatives, and synthetic (-)-cinerin A were found to have antiproliferative effect at different levels. Bicyclooctanoids as well as kaurenoic acid exhibited activity against all human cancer cells while benzofuranoids showed selective activity against HeLa. Furthermore, compounds (-)-cinerin A and kaurenoic acid exhibited total lethal effect against all-five cell lines and PC-3, Hep-2, and A549 cell lines, respectively. Test compounds exhibiting antiproliferative activity showed interesting results, which would promote their use as lead compounds on further studies for anticancer agents development.

  2. Non-synergistic cytotoxic effects of Fusarium and Alternaria toxin combinations in Caco-2 cells.

    Science.gov (United States)

    Vejdovszky, Katharina; Warth, Benedikt; Sulyok, Michael; Marko, Doris

    2016-01-22

    Exposure of humans and animals to mycotoxins via food and feed generally involves a conglomeration of compounds contaminating the consumed products. Investigations on combinatory effects of mycotoxins are therefore of great importance. In this study, cytotoxic effects of binary mixtures of the Fusarium toxins enniatin B, aurofusarin, deoxynivalenol, nivalenol and zearalenone, and tenuazonic acid produced by Alternaria spp., were evaluated by the WST-1 assay in the colorectal carcinoma cell-line Caco-2 after 24h of incubation. The selection of these mycotoxins was based on typically occurring natural contamination patterns in grains. Aurofusarin, which can be found abundantly in contaminated foodstuff and has not been toxicologically characterized properly so far, showed pronounced cytotoxicity, decreasing the mitochondrial activity at 10μM to 51% compared to a solvent control. Combinations of other mycotoxins with aurofusarin showed additive effects. In contrast, binary mixtures of enniatin B, deoxynivalenol, nivalenol and zearalenone at cytotoxic concentrations, predominantly resulted in antagonistic effects. Binary combinations of these four Fusarium toxins with tenuazonic acid also revealed interacting effects leading to a decrease in cytotoxicity, compared to expected combinatory effects. Especially in combination with deoxynivalenol, tenuazonic acid was found to significantly reduce the cytotoxicity of this mycotoxin in Caco-2 cells. Synergistic effects were not observed for any toxin combination under the chosen conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells.

    Science.gov (United States)

    Dangkong, Darinee; Limpanasithikul, Wacharee

    2015-02-01

    Doxorubicin is a chemotherapy agent used in non-Hodgkin's lymphoma but side effects limit its use. Citral is a mixture of neral and geranial found in essential oils of lemon grass. We evaluated the activity of citral, doxorubicin, and combination on cytotoxicity, apoptosis, and anti-proliferative effects using human lymphoma Ramos cells. Cells were treated with doxorubicin alone or in combination with citral (10, 20, and 40 μM). Cytotoxic and apoptosis studies were done after 24 and 18 h incubations, respectively. Cytotoxic effects of citral on normal human peripheral blood mononuclear cells (PBMCs) were also investigated for its safety. Changes in the expression of BCL-2 family genes were analyzed by quantitative RT-PCR. Citral had cytotoxicity on cells with an IC50 value of 77.19 ± 4.95 µM. Citral at concentrations of 10, 20, and 40 µM additively increased the cytotoxic and apoptotic effects of doxorubicin, leading to decreased IC50 (µM) of the drug from 2.50 ± 0.01 to 2.16 ± 0.03, 1.90 ± 0.04, and 1.23 ± 0.04, respectively. Enhanced cytotoxicity was not observed in normal human PBMCs. Citral (40 µM) in combination with doxorubicin (1.5 µM) increased the expression of pro-apoptotic protein BAK but significantly decreased the expression of anti-apoptotic protein BCL-XL to 5.26-fold compared with doxorubicin-treated cells. It did not change the anti-proliferative activity of drug. Citral potentiated cytotoxicity of doxorubicin by increasing apoptotic effects. We conclude that citral may have beneficial effects in patients with B cell lymphoma treated with chemotherapy.

  4. Cytotoxic effects of mineral trioxide aggregate, calcium enriched mixture cement, Biodentine and octacalcium pohosphate on human gingival fibroblasts

    Directory of Open Access Journals (Sweden)

    Eshagh

    2016-06-01

    Full Text Available Background. This in vitro study compared the effects of mineral trioxide aggregate (MTA, calcium enriched mixture (CEM cement, Biodentine (BD and octacalcium phosphate (OCP on the viability of human gingival fibroblasts (HGFs. Methods. After completion of the setting time of the materials under study, fibroblasts were placed in 24-well insert plates and 1 mg of each material was added to the respective wells. The plates were then incubated at 37°C. The inserts were removed at 24, 48 and 168 hours and 2,5-diphenyltetrazolium bromide was added to assess cytotoxicity via the MTT colorimetric assay. Data were analyzed at different time intervals using repeated-measures ANOVA, followed by the Bonferroni test at three levels of significance of P < 0.05, P < 0.01 and P < 0.001. Results. Cytotoxicity of the materials under study was not significantly different at 24 and 48 hours compared to the control group. However, at 168 hours, a significant difference was noted between MTA (P< 0.05 and Biodentine (P < 0.01 and the control group. Conclusion. Cytotoxicity of MTA, CEM, Biodentine and OCP against HGFs was similar to that of the control group at 24 and 48 hours. Over time, MTA and Biodentine exhibited less cytotoxicity than other materials.

  5. Chemical composition and in vitro cytotoxic, genotoxic effects of essential oil from Urtica dioica L.

    Science.gov (United States)

    Gül, Süleyman; Demirci, Betül; Başer, Kemal Hüsnü Can; Akpulat, H Aşkin; Aksu, Pinar

    2012-05-01

    The aim of this study was to determine the chemical composition of Urtica dioica essential oil, and to evaluate its cytotoxic and genotoxic effects, using cytogenetic tests such as the cytokinesis-block micronucleus assay and chromosomal aberration analysis in human lymphocyte cultures in vitro. GC-MS analysis of U. dioica essential oil identified 43 compounds, representing 95.8% of the oil. GC and GC-MS analysis of the essential oil of U. dioica revealed that carvacrol (38.2%), carvone (9.0%), naphthalene (8.9%), (E)-anethol (4.7%), hexahydrofarnesyl acetone (3.0%), (E)-geranyl acetone (2.9%), (E)-β-ionone (2.8%) and phytol (2.7%) are the main components, comprising 72.2% of the oil. A significant correlation was found between the concentration of essential oil and the following: chromosomal aberrations, micronuclei frequency, apoptotic cells, necrotic cells, and binucleated cells.

  6. A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

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    Víctor A. Solarte

    2015-01-01

    Full Text Available Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–254, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90% in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

  7. In Vitro Evaluations of Cytotoxicity of Eight Antidiabetic Medicinal Plants and Their Effect on GLUT4 Translocation

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    Sleman Kadan

    2013-01-01

    Full Text Available Despite the enormous achievements in conventional medicine, herbal-based medicines are still a common practice for the treatment of diabetes. Trigonella foenum-graecum, Atriplex halimus, Olea europaea, Urtica dioica, Allium sativum, Allium cepa, Nigella sativa, and Cinnamomum cassia are strongly recommended in the Greco-Arab and Islamic medicine for the treatment and prevention of diabetes. Cytotoxicity (MTT and LDH assays of the plant extracts was assessed using cells from the liver hepatocellular carcinoma cell line (HepG2 and cells from the rat L6 muscle cell line. The effects of the plant extracts (50% ethanol in water on glucose transporter-4 (GLUT4 translocation to the plasma membrane was tested in an ELISA test on L6-GLUT4myc cells. Results obtained indicate that Cinnamomon cassia is cytotoxic at concentrations higher than 100 μg/mL, whereas all other tested extracts exhibited cytotoxic effects at concentrations higher than 500 μg/mL. Exposing L6-GLUT4myc muscle cell to extracts from Trigonella foenum-graecum, Urtica dioica, Atriplex halimus, and Cinnamomum verum led to a significant gain in GLUT4 on their plasma membranes at noncytotoxic concentrations as measured with MTT assay and the LDH leakage assay. These findings indicate that the observed anti-diabetic properties of these plants are mediated, at least partially, through regulating GLUT4 translocation.

  8. In Vitro Evaluations of Cytotoxicity of Eight Antidiabetic Medicinal Plants and Their Effect on GLUT4 Translocation

    Science.gov (United States)

    Kadan, Sleman; Saad, Bashar; Sasson, Yoel; Zaid, Hilal

    2013-01-01

    Despite the enormous achievements in conventional medicine, herbal-based medicines are still a common practice for the treatment of diabetes. Trigonella foenum-graecum, Atriplex halimus, Olea europaea, Urtica dioica, Allium sativum, Allium cepa, Nigella sativa, and Cinnamomum cassia are strongly recommended in the Greco-Arab and Islamic medicine for the treatment and prevention of diabetes. Cytotoxicity (MTT and LDH assays) of the plant extracts was assessed using cells from the liver hepatocellular carcinoma cell line (HepG2) and cells from the rat L6 muscle cell line. The effects of the plant extracts (50% ethanol in water) on glucose transporter-4 (GLUT4) translocation to the plasma membrane was tested in an ELISA test on L6-GLUT4myc cells. Results obtained indicate that Cinnamomon cassia is cytotoxic at concentrations higher than 100 μg/mL, whereas all other tested extracts exhibited cytotoxic effects at concentrations higher than 500 μg/mL. Exposing L6-GLUT4myc muscle cell to extracts from Trigonella foenum-graecum, Urtica dioica, Atriplex halimus, and Cinnamomum verum led to a significant gain in GLUT4 on their plasma membranes at noncytotoxic concentrations as measured with MTT assay and the LDH leakage assay. These findings indicate that the observed anti-diabetic properties of these plants are mediated, at least partially, through regulating GLUT4 translocation. PMID:23606883

  9. Cytotoxicity effect of Zataria multiflora Boiss. on two human colon carcinoma cell lines

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    F. Sharififar

    2017-10-01

    Full Text Available Background and objectives: Natural products are one of the major sources for investigations of novel medicines. Zataria multiflora Boiss (ZM has shown pharmacological activities especially in gastrointestinal tract; however, there are limited studies about its cytotoxicity effects. In this study, the effect of Zataria multiflora was examined on two colon cancer cell lines (SW-48 and HT-29. Methods: Hydro-alcoholic extract of ZM and its fractions including chloroform, petroleum ether and methanol extract were prepared by warm maceration method. Different concentrations were prepared and examined on SW-48 and HT-29 cell lines using 2-(4, 5-dimethylthiazol-2-yl 2, 5-diphenyltetrazolium bromide (MTT assay. Results: The results of the present study have shown the cytotoxic effect of some fractions of ZM. The most considerable cytotoxic effect was shown against HT-29 cell line. Also, total ZM extract and the petroleum ether fraction demonstrated cytotoxic effects with IC50 values of 44.22 and 33.42 µg/ml on SW-48 and HT-29 cell lines, respectively. Conclusion: Zataria multiflora was cytotoxic to against colon cancer cell lines HT-29 and SW-48.

  10. In vitro antimicrobial and cytotoxic effects of Anacardium occidentale and Mangifera indica in oral care

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    Geethashri Anand

    2015-01-01

    Full Text Available Background: Oral health is an integral and important component of general health. Infectious diseases such as caries, periodontal, and gingivitis indicate the onset of imbalance in homeostasis between oral micro biota and host. The present day medicaments used in oral health care have numerous side effects. The uses of herbal plants as an alternative have gained popularity due to side effects of antibiotics and emergence of multidrug resistant strains. Anacardium occidentale (cashew and Mangifera indica (mango have been used as traditional oral health care measures in India since time immemorial. Materials and Methods: The ethanol extracts of cashew and mango leaves were obtained by maceration method. The antimicrobial activity was evaluated by clear zone produced by these plant extracts against Enterococcus faecalis, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Candida albicans in agar plate method, determination of minimum inhibitory concentration (MIC, minimum bactericidal/fungicidal concentration (MBC/MFC, and suppression of biofilm. The cytotoxic effects of plants extract was determined by microculture tetrazolium assay on human gingival fibroblast and Chinese hamster lung fibroblast (V79 cell lines. Results: Cashew and mango leaf extract significantly (P < 0.05 produced larger zone of inhibition against test pathogens when compared to povidone---iodine-based mouth rinses. Although the MIC and MBC/MFC values of mouth rinses were effective in lower concentrations; plant extracts significantly (P < 0.001 suppressed the biofilms of oral pathogens. The leaf extracts were less cytotoxic (P < 0.001 compared to mouth rinses. Conclusions: Plant extracts are superior to the mouth rinses and have a promising role in future oral health care.

  11. In Vitro Cytotoxic Evaluation of MgO Nanoparticles and Their Effect on the Expression of ROS Genes

    Science.gov (United States)

    Kumaran, Rangarajulu Senthil; Choi, Yong-Keun; Singh, Vijay; Song, Hak-Jin; Song, Kyung-Guen; Kim, Kwang Jin; Kim, Hyung Joo

    2015-01-01

    Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS), glutathione S-transferase (GST) and catalase, were quantified using real-time polymerase chain reactions (molecular level) and molecular beacon technologies (cellular level). The monodispersed MgO nanoparticles, 20 nm in size, were used to treat human cancer cell lines (liver cancer epithelial cells) at different concentrations (25, 75 and 150 µg/mL) and incubation times (24, 48 and 72 h). Both the genetic and cellular cytotoxic screening methods produced consistent results, showing that GST and catalase ROS gene expression was maximized at 150 µg/mL nanoparticle treatment with 48 h incubation. However, the genotoxic effect of MgO nanoparticles was not significant compared with control experiments, which indicates its significant potential applications in nanomedicine as a diagnostic and therapeutic tool. PMID:25854426

  12. In Vitro Cytotoxic Evaluation of MgO Nanoparticles and Their Effect on the Expression of ROS Genes

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    Rangarajulu Senthil Kumaran

    2015-04-01

    Full Text Available Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS, glutathione S-transferase (GST and catalase, were quantified using real-time polymerase chain reactions (molecular level and molecular beacon technologies (cellular level. The monodispersed MgO nanoparticles, 20 nm in size, were used to treat human cancer cell lines (liver cancer epithelial cells at different concentrations (25, 75 and 150 µg/mL and incubation times (24, 48 and 72 h. Both the genetic and cellular cytotoxic screening methods produced consistent results, showing that GST and catalase ROS gene expression was maximized at 150 µg/mL nanoparticle treatment with 48 h incubation. However, the genotoxic effect of MgO nanoparticles was not significant compared with control experiments, which indicates its significant potential applications in nanomedicine as a diagnostic and therapeutic tool.

  13. 1 Nigerian Journal of Chemical Research Vol. 18, 2013 Cytotoxicity ...

    African Journals Online (AJOL)

    MASANAWA

    A study on cytotoxicity of Citrullus lanatus (water melon) extracts on Artemia salina (Brine shrimp test (BST) was carried out using extraction and cytotoxicity standard procedures, to determine cytotoxic effects of the plant extracts . The stems, leaves and seeds of light bark variety of C. lanatus were collected from karfi ...

  14. Prolonged cytotoxic effect of aqueous extracts from dried viscum album on bladder cancer cells.

    Science.gov (United States)

    Hunziker-Basler, N; Zuzak, T J; Eggenschwiler, J; Rist, L; Simões-Wüst, A P; Viviani, A

    2007-03-01

    Aqueous extracts from whole dried mistletoe (Viscum album L., Iscucin) are often used in anti-cancer treatment. We studied the effect of extracts obtained from mistletoe bushes that grew on different host trees on bladder cancer cells by means of MTT-colorimetric cell proliferation/survival assays. The extracts possessed concentration-dependent cytotoxic properties whose extent varied with the host tree, but did not always correlate with the corresponding mistletoe lectin content. A 2-hours treatment of bladder cancer cells triggered a later, strong cytotoxic effect. This prolonged effect suggests that instillation with Iscucin has therapeutic potential for bladder cancer patients.

  15. The Effect of Ascorbic Acid over the Etoposide- and Temozolomide-Mediated Cytotoxicity in Glioblastoma Cell Culture: A Molecular Study.

    Science.gov (United States)

    Gokturk, Dilek; Kelebek, Hasim; Ceylan, Seda; Yilmaz, Dervis Mansuri

    2018-01-01

    Glioblastoma (GBM) is one of the lethal central nervous system tumors. One of the widely used chemical agents for the treatment of glioblastoma is temozolomide. It is an orally administered, deoxyribonucleic acid (DNA) alkylating agent. DNA alkylation triggers the death of tumor cells. However, some tumor cells are able to repair this type of DNA damage and thus lower the therapeutic effect of temozolomide. Laboratory and clinical studies indicate that temozolomide"s anticancer effects might be strengthened when combined with other chemotherapeutic agents like etoposide or antioxidant agents like ascorbic acid. In this study, we aimed to evaluate the cytotoxic and oxidative stress effects of ascorbic acid (1000 ?M), temozolomide (100 ?M) and etoposide (25 ?M) agents alone and in dual and triple combinations in a glioblastoma U87 MG cell culture. The cytotoxic and oxidative stress effects were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) and liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis methods. Cytotoxicity tests showed that etoposide, temozolomide, "etoposide+ascorbic acid", "temozolomide+ascorbic acid", "temozolomide+etoposide" and "temozolomide+etoposide+ascorbic acid" combinations have anti-proliferative effects. The maximum anti-proliferation response was observed in the "temozolomide+etoposide+ascorbic acid"-added group. Similarly LCMS/ MS analyses showed that minimum oxidative DNA damage occurred in the "temozolomide+etoposide+ascorbic acid"-added group. Ascorbic acid decreases the cytotoxic and genotoxic effect of etoposide and etoposide-temozolomide combination but it has no meaningful effect on temozolomide"s toxicity.

  16. In Vitro Cytotoxicity Test and Surface Characterization of CoCrW Alloy in Artificial Saliva Solution for Dental Applications.

    Science.gov (United States)

    Souza, Klester Santos; Jaimes, Ruth Flavia Vera Villamil; Rogero, Sizue Otta; Nascente, Pedro Augusto de Paula; Agostinho, Silvia Maria Leite

    2016-01-01

    In order to evaluate its application as a dental prosthesis material, a CoCrW alloy was subjected to in vitro cytotoxicity test, surface characterization and electrochemical studies performed in artificial saliva and 0.15 mol.L-1 NaCl medium. The used techniques were: anodic polarization curves, chronoamperometric measurements, electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) analysis and X-ray photoelectron spectroscopy (XPS). Cytotoxicity test was also performed. The electrochemical behavior of CoCrW alloy was compared in both studied media, from corrosion potential (Ecorr) to a 600 mV anodic overvoltage. From the electrochemical measurements it was observed that the CoCrW alloy in both media presents only generalized corrosion. SEM and EDS analysis showed that the alloy presents carbide niobium and silicon and manganese oxides as nonmetallic inclusions. XPS results indicated that cobalt does not significantly contribute to the passivating film formation. Cytotoxicity test showed no cytotoxic character of CoCrW alloy. These results suggest that the CoCrW alloy can be used as biomaterial to be applied as prosthesis in dental implants.

  17. Intracellular ATP concentration contributes to the cytotoxic and cytoprotective effects of adenosine.

    Directory of Open Access Journals (Sweden)

    Shujue Li

    Full Text Available Extracellular adenosine (ADE interacts with cells by two pathways: by activating cell surface receptors at nanomolar/micromolar concentrations; and by interfering with the homeostasis of the intracellular nucleotide pool at millimolar concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the underlying mechanisms remain unclear. In the present study, the effects of adenosine-mediated ATP on cell viability were investigated. Adenosine treatment was found to be cytoprotective in the low intracellular ATP state, but cytotoxic under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection rely on adenosine-derived ATP formation, but not via the adenosine receptor pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP generation. These data provide a new pathway by which adenosine exerts dual biological effects on cell viability, suggesting an important role for adenosine as an ATP precursor besides the adenosine receptor pathway.

  18. Size Effect on the Cytotoxicity of Layered Black Phosphorus and Underlying Mechanisms.

    Science.gov (United States)

    Zhang, Xuejiao; Zhang, Ziming; Zhang, Siyu; Li, Dengyu; Ma, Wei; Ma, ChuanXin; Wu, Fengchang; Zhao, Qing; Yan, Qingfeng; Xing, Baoshan

    2017-08-01

    A systematic cytotoxicity study of layered black phosphorus (BP) is urgently needed before moving forward to its potential biomedical applications. Herein, bulk BP crystals are synthesized and exfoliated into layered BP with different lateral size and thickness. The cytotoxicity of as-exfoliated layered BP is evaluated by a label-free real-time cell analysis technique, displaying a concentration-, size-, and cell type-dependent response. The IC50 values can vary by 40 and 30 times among the BP sizes and cell types, respectively. BP-1 with the largest lateral size and thickness has the highest cytotoxicity; whereas the smallest BP-3 only shows moderate toxicity. The sensitivity of three tested cell lines follows the sequence of 293T > NIH 3T3 > HCoEpiC. Two possible mechanisms for BP to induce cytotoxicity are proposed and verified: (1) the generation of intracellular reactive oxygen species (ROS) is detected by a ROS sensitive probe using the inverted fluorescence microscopy and flow cytometry; (2) the interaction of layered BP and model cell membrane is examined by quartz crystal microbalance with dissipation, illustrating the disruption of cell membrane integrity especially by the largest BP-1. This systematic study of BP's cytotoxicity will shed light on its future biomedical and environmental applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells.

    Science.gov (United States)

    de Vasconcelos, Alana; Campos, Vinicius Farias; Nedel, Fernanda; Seixas, Fabiana Kömmling; Dellagostin, Odir A; Smith, Kevin R; de Pereira, Cláudio Martin Pereira; Stefanello, Francieli Moro; Collares, Tiago; Barschak, Alethéa Gatto

    2013-06-01

    Recent studies report that chalcones exhibit cytotoxicity to human cancer cell lines. Typically, the form of cell death induced by these compounds is apoptosis. In the context of the discovery of new anticancer agents and in light of the antitumour potential of several chalcone derivatives, in the present study, we synthesized and tested the cytotoxicity of six chalcone derivatives on human colon adenocarcinoma cells. Six derivatives of 3-phenyl-1-(thiophen-2-yl) prop-2-en-1-one were prepared and characterized on the basis of their (1) H and (13) C NMR spectra. HT-29 cells were treated with synthesized chalcones on two concentrations by three different incubation times. Cells were evaluated by cell morphology, Tetrazolium dye (MTT) colorimetric assay, live/dead, flow cytometry (annexin V) and gene expression analyses to determine the cytotoxic way. Chalcones 3-(4-bromophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C06) and 3-(2-nitrophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C09) demonstrated higher cytotoxicity than other chalcones as shown by cell morphology, live/dead and MTT assays. In addition, C06 induced apoptosis on flow cytometry annexin V assay. These data were confirmed by a decreased expression of anti-apoptotic genes and increased pro-apoptotic genes. Our findings indicate in summary that the cytotoxic activity of chalcone C06 on colorectal carcinoma cells occurs by apoptosis. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Metabolism and cytotoxic effects of phosphatidylcholine hydroperoxide in human hepatoma HepG2 cells.

    Science.gov (United States)

    Suzuki, Yuuri; Nakagawa, Kiyotaka; Kato, Shunji; Tatewaki, Naoto; Mizuochi, Shunsuke; Ito, Junya; Eitsuka, Takahiro; Nishida, Hiroshi; Miyazawa, Teruo

    2015-03-20

    In this study, we investigated cellular uptake and metabolism of phosphatidylcholine hydroperoxide (PCOOH) in human hepatoma HepG2 cells by high performance liquid chromatography-tandem mass spectrometry, and then evaluated whether PCOOH or its metabolites cause pathophysiological effects such as cytotoxicity and apoptosis. Although we found that most PCOOH was reduced to PC hydroxide in HepG2 cells, the remaining PCOOH caused cytotoxic effects that may be mediated through an unusual apoptosis pathway. These results will enhance our fundamental understanding of how PCOOH, which is present in oxidized low density lipoproteins, is involved in the development of atherosclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Evaluation of cytotoxic and antimicrobial effects of two Bt Cry proteins on a GMO safety perspective.

    Science.gov (United States)

    Farias, Davi Felipe; Viana, Martônio Ponte; de Oliveira, Gustavo Ramos; Beneventi, Magda Aparecida; Soares, Bruno Marques; Pessoa, Claudia; Pessoa, Igor Parra; Silva, Luciano Paulino; Vasconcelos, Ilka Maria; de Sá, Maria Fátima Grossi; Carvalho, Ana Fontenele Urano

    2014-01-01

    Studies have contested the innocuousness of Bacillus thuringiensis (Bt) Cry proteins to mammalian cells as well as to mammals microbiota. Thus, this study aimed to evaluate the cytotoxic and antimicrobial effects of two Cry proteins, Cry8Ka5 (a novel mutant protein) and Cry1Ac (a widely distributed protein in GM crops). Evaluation of cyto- and genotoxicity in human lymphocytes was performed as well as hemolytic activity coupled with cellular membrane topography analysis in mammal erythrocytes. Effects of Cry8Ka5 and Cry1Ac upon Artemia sp. nauplii and upon bacteria and yeast growth were assessed. The toxins caused no significant effects on the viability (IC50 > 1,000 µg/mL) or to the cellular DNA integrity of lymphocytes (no effects at 1,000 µg/mL). The Cry8Ka5 and Cry1Ac proteins did not cause severe damage to erythrocytes, neither with hemolysis (IC50 > 1,000 µg/mL) nor with alterations in the membrane. Likewise, the Cry8Ka5 and Cry1Ac proteins presented high LC50 (755.11 and >1,000 µg/mL, resp.) on the brine shrimp lethality assay and showed no growth inhibition of the microorganisms tested (MIC > 1,000 µg/mL). This study contributed with valuable information on the effects of Cry8Ka5 and Cry1Ac proteins on nontarget organisms, which reinforce their potential for safe biotechnological applications.

  2. Cytotoxic effects and morphological changes of silver nanoparticles in CHO-K1 cells

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    Masoumeh Heshmati

    2015-11-01

    Full Text Available Background: Silver nanoparticles are of interest to be used as antimicrobial agents in medical care, wound dressings and cosmetics. Despite the fact that AgNPs are among the most commercialized nano materials owing to their specific antimicrobial properties, there is limited information about their risk assessment and possible hazards to human health and environment. Thus, this study was carried out to evaluate the cytotoxicity and morphological changes of different concentrations of two samples of commercialized silver nanoparticles (A and B in CHO-K1 cells using MTT assay. Methods: The cytotoxicity effect of silver nanoparticles AgNP-A (19.6 nm in diameter and AgNP-B (15 nm in diameter on CHO-K1 was evaluated in the range of 0.005-500 µg/ml after 24 hours of treatment using MTT assay. The morphological changes of treated cells were examined by light microscopy. Results: Based on the results of cytotoxicity by MTT assay, reduced viability of cells and cytotoxicity were observed. The 50% inhibitory concentration (IC50 of silver nanoparticles was recorded at 100 and 10 µg/ml for AgNP-A and AgNP-B, respectively. Moreover, microscopic observations indicated clear morphological changes of treated cells. Conclusion: Concentration and physicochemical properties of silver nanoparticles like size, shape, surface area, coating and zeta potential play a role in cytotoxicity and morphological changes of treated cells.

  3. Cytotoxicity Effects of Amoora rohituka and chittagonga on Breast and Pancreatic Cancer Cells

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    Leo L. Chan

    2011-01-01

    Full Text Available Chemotherapeutic agents for cancer are highly toxic to healthy tissues and hence alternative medicine avenues are widely researched. Majority of the recent studies on alternative medicine suggested that Amoora rohituka possesses considerable antitumor and antibacterial properties. In this work, rohituka and chittagonga, fractionated with petroleum ether, dichloromethane, and ethanol, were explored for their anticancer potential against two breast cancer (MCF-7 and HTB-126 and three pancreatic cancer (Panc-1, Mia-Paca2, and Capan1. The human foreskin fibroblast, Hs68, was also included. Cytotoxicity of each extract was analyzed using the MTT assay and label-free photonic crystal biosensor assay. A concentration series of each extract was performed on the six cell lines. For MCF-7 cancer cells, the chittagonga (Pet-Ether and CH2Cl2 and rohituka (Pet-Ether extracts induced cytotoxicity; the chittagonga (EtoAC and rohituka (MeOH extracts did not induce cytotoxicity. For HTB126, Panc-1, Mia-Paca2, and Capan-1 cancer cells, only the chittagonga CH2Cl2 extract showed a significant cytotoxic effect. The extracts were not cytotoxic to normal fibroblast Hs68 cells, which may be correlated to the specificity of Amoora extracts in targeting cancerous cells. Based on these results, further examination of the potential anticancer properties Amoora species and the identification of the active ingredients of these extracts is warranted.

  4. Investigation of cytotoxic and mutagenic effects of Malpighia glabra L. (barbados cherry fruit pulp and vitamin C on plant and animal test systems Investigação do efeito citotóxico e mutagênico da polpa da fruta Malpighia glabra L. (acerola e da vitamina C em sistema teste vegetal e animal

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    Elisângela Düsman

    2012-06-01

    Full Text Available Fruits are important sources of nutrients in human diet, and Barbados Cherry (Malpighia glabra L. is of particular interest due to its high content of antioxidants. Diets rich in fruits and vegetables protect individuals against diseases and cancer, but excessive intake of vitamins may act as pro-oxidant and generate changes in DNA. To evaluate the effect of different in natura (BAN and frozen (BAF Barbados Cherry pulp concentrations and synthetic vitamin C in liquid form (VC on the chromosome level and the cell cycle division, root meristeme cells of Allium cepa L. and bone marrow cells of Wistar rats Rattus norvegicus, were used as test system. In Allium cepa L., BAN, at the highest concentration (0.4 mg.mL-1 and BAF, at the lowest concentration (0.2 mg.mL-1, inhibited cell division, and there was recovery of cell division after the recovery period in water only for BAN. In the Wistar rats, all treatments with Barbados Cherry, either acute or subchronic, were not cytotoxic or mutagenic; only the highest concentration of VC increased significantly the rate of chromosomal abnormalities. The data obtained are important to reinforce the use of Barbados Cherry fruit in the diet.As frutas são importantes fontes de nutrientes na dieta humana e a Acerola (Malpighia glabra L. é de particular interesse devido ao seu alto teor de antioxidantes. Dietas ricas em frutas e legumes protegem os indivíduos contra doenças e câncer, mas a ingestão excessiva de vitaminas pode atuar como pró-oxidante e gerar alterações no DNA. Para avaliar o efeito de diferentes concentrações da polpa in natura da Acerola (BAN e congelada (BAF, e da vitamina C sintética na forma líquida (VC, em nível cromossômico e sobre o ciclo de divisão celular, foram utilizadas células meristemáticas de raiz de Allium cepa L. e células da medula óssea de ratos Wistar, Rattus norvegicus, como sistema teste. Em Allium cepa L., BAN, na maior concentração (0,4 mg.mL-1 e BAF

  5. Adjuvant antiproliferative and cytotoxic effect of aloin in irradiated HeLaS3 cells

    Science.gov (United States)

    Nićiforović, A.; Adžić, M.; Zarić, B.; Radojčić, M. B.

    2007-09-01

    Naturally occurring phytoanthracycline, aloin, was used to radiosensitize HeLaS3 human cervix carcinoma cells. The results indicated that the cytotoxic adjuvant effect of aloin was synergistic with gammaionizing radiation at all drug concentrations and comparable to the cytotoxicity of 5-10 Gy ionizing radiation alone. Radiosensitization of HeLaS3 cells was achieved by 60 μM aloin, which reduced the IC50 dose of ionizing radiation from 3.4 to 2 Gy. Ionizing radiation and aloin alone or in combination are shown to cause perturbation of the HeLaS3 cell-cycle and increase the percentage of cells in the DNA synthesis (S) phase of the cell cycle. While either of the agents applied alone causes programmed cell death by apoptosis, the simultaneous cell damage by both agents through the altered redox balance compromised cell capacity to conduct this program and led to synergic cytotoxic cell death by necrosis.

  6. The Evaluation of Cytotoxic and Regenerative Effects of Recently Used Pulpotomy Materials; at Cellular Level

    OpenAIRE

    Özbay Yavlal, Gizem; Kargül, Betül

    2015-01-01

    Objective: To compare osteo/odontogenic differentiation (regeneration) capacities of a new amputation material named as Biodentine TM and the Pro-ROOT MTA and cytotoxic effects of Biodentine TM, Pro-ROOT MTA, Formokreazol (FK), Ferric Sulphate (FS) and Calcium Hydroxide (Ca(OH)2) on mesenchymal stem cells derived from dental pulp of 50 primary teeth with completed root resorption. Method: Cell cultures were prepared. On the 1st, 3rd and 7th day, cytotoxicity of MTA, Biodentine TM, FK, FS, and...

  7. Investigation of cytotoxic, apoptosis-inducing, genotoxic and protective effects of the flavonoid rutin in HTC hepatic cells.

    Science.gov (United States)

    Cristina Marcarini, Juliana; Ferreira Tsuboy, Marcela Stefanini; Cabral Luiz, Rodrigo; Regina Ribeiro, Lucia; Beatriz Hoffmann-Campo, Clara; Ségio Mantovani, Mário

    2011-07-01

    Rutin is a flavonoid with antioxidant, vasodilatory, anti-inflammatory and immune-stimulating activities. To study the toxicity of rutin and its protective effect, this work investigated the cytotoxic, apoptosis-inducing, genotoxic and protective effects of rutin in HTC cells. In the MTT assay, the highest concentration tested (810 μM) showed cytotoxicity after 72 h of treatment, where cell viability and cell proliferation was diminished. None of the concentrations of rutin tested induced apoptosis after 24h treatment. The highest concentration of rutin after 24h treatment induced DNA damage, shown in the comet assay, but did have a genotoxic effect in the micronucleus test. Rutin was tested against the pro-carcinogenic agent benzo(a)pyrene, at concentrations of 90, 270 and 810 μM, and was found to reduce induced DNA damage significantly. This protective effect of rutin against a pro-carcinogen, suggests an important biological activity for this compound, which can contribute to human health through the diet. Copyright © 2010 Elsevier GmbH. All rights reserved.

  8. Antioxidative, antimicrobial and cytotoxic effects of the phenolics of Leea indica leaf extract

    Science.gov (United States)

    Rahman, Md. Atiar; Imran, Talha bin; Islam, Shahidul

    2012-01-01

    This study investigated the phytochemical, antioxidative, antimicrobial and cytotoxic effects of Leea indica leaf ethanol extract. Phytochemical values namely total phenolic and flavonoid contents, total antioxidant capacity, DPPH radical scavenging effect, FeCl3 reducing power, DMSO superoxide scavenging effect and Iron chelating effects were studied by established methods. Antibacterial, antifungal and cytotoxic effects were screened by disk diffusion technique, food poison technique and brine shrimp bioassay, respectively. Results showed the total phenolic content 24.00 ± 0.81 g GAE/100 g, total flavonoid content 194.68 ± 2.43 g quercetin/100 g and total antioxidant capacity 106.61 ± 1.84 g AA/100 g dry extract. Significant (P extract showed significant (P extract inhibited the growth of Aspergillus flavus, Candida albicans and Fusarium equisetii by 38.09 ± 0.59, 22.58 ± 2.22, and 22.58 ± 2.22%, respectively. The extract showed a significant LC50 value compared to vincristine sulfate in cytotoxic assay. The results evidenced the potential antioxidative, antimicrobial and cytotoxic capacities of Leea inidica leaf extract to be processed for pharmaceutical use. PMID:23961238

  9. Cytotoxic effects of five commonly abused skin toning (bleaching) creams on Allium cepa root tip mitosis.

    Science.gov (United States)

    Udengwu, O S; Chukwujekwu, J C

    2008-09-15

    The Allium test was used to study the cytotoxic effects of five commonly abused skin toning creams--Ikb, Tura, Top gel, Dorot and Mililo. These creams are commonly used by some black skinned people (especially the females) as skin lightening (bleaching) agents. The results showed that all the five bleaching creams were mito-depressive in action. They exhibited both chromatoclassic and mitoclassic effects. Their depressive effects were found to increase with duration of treatment. The induced abnormalities included chromosome contraction, spindle breakages, c-metaphase, star anaphase, chromosome stickiness and sticky bridges, precocious chromosome movement as well as endomitosis. It is suggested that since all eukaryotic cells are basically the same, these observed abnormalities could be similar to the effects these chemicals have on human skin when they are applied. Some of these are known to cause alteration in melanin formation as well as the biosynthesis of the enzyme tyrosinase. Furthermore, since certain points on the chromosomes called fragile sites have been implicated in oncogenesis, the observed abnormalities may be part of (or include) the switching on mechanisms of such genes, which could be responsible for the transformation of normal skin cells to malignant cells in those who abuse these creams.

  10. Effect of strontium addition and chitosan concentration variation on cytotoxicity of chitosan-alginate-carbonate apatite based bone scaffold

    Science.gov (United States)

    Perkasa, Rilis Eka; Umniati, B. Sri; Sunendar, Bambang

    2017-09-01

    Bone scaffold is one of the most important component in bone tissue engineering. Basically, bone scaffold is a biocompatible structure designed to replace broken bone tissue temporarily. Unlike conventional bone replacements, an advanced bone scaffold should be bioactive (e.g: supporting bone growth) and biodegradable as new bone tissue grow, while retain its mechanical properties similarity with bone. It is also possible to add more bioactive substrates to bone scaffold to further support its performance. One of the substrate is strontium, an element that could improve the ability of the bone to repair itself. However, it must be noted that excessive consumption of strontium could lead to toxicity and diseases, such as osteomalacia and hypocalcemia. This research aimed to investigate the effect of strontium addition to the cytotoxic property of chitosan-alginate-carbonate apatite bone scaffold. The amount of strontium added to the bone scaffold was 5% molar of the carbonate apatite content. As a control, bone scaffold without stronsium (0% molar) were also made. The effect of chitosan concentration variation on the cytotoxicity were also observed, where the concentration varies on 1% and 3% w/v of chitosan solution. The results showed an optimum result on bone scaffold sample with 5% molar of strontium and 3% chitosan, where 87.67% cells in the performed MTS-Assay cytotoxicity testing survived. This showed that the use of up to 5% molar addition of strontium and 3% chitosan could enhance the survivability of the cell.

  11. Cytotoxic Effect of Ethanolic Extract of Sarang Semut (Myrmecodia pendens on HeLa Cervix Cancer Cell Line In Vitro Experimental Study

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    Dina Fatmawati

    2011-12-01

    Design and Method: The method was quasi experimental with post test only non equivalent control group design. HeLa cell was divided into two groups. The first group as positive control with doxorubicin, second group as treatment with ethanolic extract of sarang semut at various concentrations. Ethanolic extract of sarang semut concentrations used were 3,91 μg/ml; 7,81 μg/ml; 15,63 μg/ml; 31,25 μg/ml; 62,50 μg/ml; 125 μg/ml; 250 μg/ml; 500 μg/ml; 1000 μg/ml. Cytotoxic effect was evaluated by direct counting method with tryphan blue dye then using probit regression analysis to find IC50 value. Result: Inhibitory concentration 50 (IC50 value ethanol extract of sarang semut was 33,28 μg/ml. Ethanol extract of sarang semut had a cytotoxicity effect categorized as the moderately active (20 ìg/ml< IC50< 100ìg/ ml. Inhibitory concentration 50 (IC50 value doxorubicin was 5,56 μg/ml. Cytotoxicity effect of doxorubisin higher than cytotoxicity effect of ethanolic extract of sarang semut. Conclusion: Ethanolic extract of sarang semut (Myrmecodia pendens had a cytotoxic effect categorized as the moderately active on HeLa cell (Sains Medika, 3(2:112-120.

  12. Neurotoxic and Cytotoxic Effects of Venom from Different Populations of the Egyptian Scorpio Maurus Palmatus

    Science.gov (United States)

    Neurotoxic and cytotoxic effects of venoms from Scorpio maurus palmatus taken from different populations were assessed for geographic based variability in toxicity and to evaluate their insecticidal potency. Scorpions were collected from four regions. Three locations were mutually isolated pockets i...

  13. Preliminary studies on cytotoxic effect of fungal taxol on cancer cell ...

    African Journals Online (AJOL)

    SERVER

    2007-06-18

    Jun 18, 2007 ... Preliminary studies on cytotoxic effect of fungal taxol on cancer cell lines. V. Gangadevi and J. Muthumary*. Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai – 600 025, Tamil Nadu, India. Accepted 19 January, 2007. Taxol is an important anticancer drug used widely ...

  14. Cytotoxic Effect on Cancerous Cell Lines by Biologically Synthesized Silver Nanoparticles

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    Balaji Kulandaivelu

    Full Text Available The biosynthesis of nanoparticles has been proposed as an environmental friendly and cost effective alternative to chemical and physical methods. Silver nanoparticles are biologically synthesized and characterized were used in the study. The invitro cytotoxic effect of biologically synthesized silver nanoparticles against MCF-7 cancer cell lines were assessed. The cytotoxic effects of the silver nanoparticles could significantly inhibited MCF-7 cancer cell lines proliferation in a time and concentration-dependent manner by MTT assay. Acridine orange, ethidium bromide (AO/EB dual staining, caspase-3 and DNA fragmentation assays were carried out using various concentrations of silver nanoparticles ranging from 1 to 100 μg/mL. At 100 μg/mL concentration, the silver nanoparticles exhibited significant cytotoxic effects and the apoptotic features were confirmed through caspase-3 activation and DNA fragmentation assays. Western blot analysis has revealed that nanoparticle was able to induce cytochrome c release from the mitochondria, which was initiated by the inhibition of Bcl-2 and activation of Bax. Thus, the results of the present study indicate that biologically synthesized silver nanoparticles might be used to treat breast cancer. The present studies suggest that these nanoparticles could be a new potential adjuvant chemotherapeutic and chemo preventive agent against cytotoxic cells. However, it necessitates clinical studies to ascertain their potential as anticancer agents.

  15. Preliminary studies on cytotoxic effect of fungal taxol on cancer cell ...

    African Journals Online (AJOL)

    Taxol is an important anticancer drug used widely in the clinical field. Some endophytic fungi were isolated from selected medicinal plants and screened for the production of taxol. The effect of cytotoxicity of fungal taxol isolated from fungal endophytes was investigated by apoptosis method. The presence of taxol in the ...

  16. Macerated-Pineapple Core Crude Extract-derived Bromelain Has Low Cytotoxic Effect in NIH-3T3 Fibroblast

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    Dewi Liliany Margaretta

    2015-08-01

    Full Text Available BACKGROUND: Bromelain is a sulfhydryl proteolytic enzyme that can hydrolyze protein, protease or peptide. Bromelain can be found in pineapple stem, fruit and core. Bromelain is composed of 212 amino acid residues with cysteine-25 forming a polypeptide chain that can hydrolyze peptide bonds by H2O. In medicine, bromelain has been developed as antibiotic, cancer drug, anti-inflammatory agent and immunomodulator. In dentistry, bromelain has potential to reduce plaque formation on the teeth and to irrigate root canal. METHODS: Pineapple core was dried for 3 days to get simplicia. Then simplicia was extracted with water solvent for 24 hours. After that, the macerated-pineapple core crude extract-derived bromelain (PCB was separated by Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE followed by Coomassie Brilliant Blue (CBB staining to ensure the presence of bromelain. In cytotoxic test, NIH-3T3 fibroblast cultures were treated with extracts in various concentrations to for 24 or 48 hours. Number of fibroblasts was calculated using 3-(4,5-dimethylthiazol-2- yl-2,5-Diphenyltetrazolium bromide (MTT assay. RESULTS: Pineapple core extraction using maceration method produced relative high yield (concentration: 1.5424 g/mL of bromelain, which was confirmed by CBB staining results with the molecular weight of 33 kDa. Based on cytotoxic test results of PCB on NIH-3T3 fibroblasts, 24-hours-incubation LD50 was 95.7 g/L, while 48-hours-incubation LD50 was 51.1 g/L. CONCLUSIONS: PCB has low cytotoxic effect in NIH-3T3 fibroblasts. KEYWORDS: bromelain, pineapple, extract, cytotoxic, MTT.

  17. In vitro cytotoxicity of Manville Code 100 glass fibers: Effect of fiber length on human alveolar macrophages

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    Jones William

    2006-03-01

    Full Text Available Abstract Background Synthetic vitreous fibers (SVFs are inorganic noncrystalline materials widely used in residential and industrial settings for insulation, filtration, and reinforcement purposes. SVFs conventionally include three major categories: fibrous glass, rock/slag/stone (mineral wool, and ceramic fibers. Previous in vitro studies from our laboratory demonstrated length-dependent cytotoxic effects of glass fibers on rat alveolar macrophages which were possibly associated with incomplete phagocytosis of fibers ≥ 17 μm in length. The purpose of this study was to examine the influence of fiber length on primary human alveolar macrophages, which are larger in diameter than rat macrophages, using length-classified Manville Code 100 glass fibers (8, 10, 16, and 20 μm. It was hypothesized that complete engulfment of fibers by human alveolar macrophages could decrease fiber cytotoxicity; i.e. shorter fibers that can be completely engulfed might not be as cytotoxic as longer fibers. Human alveolar macrophages, obtained by segmental bronchoalveolar lavage of healthy, non-smoking volunteers, were treated with three different concentrations (determined by fiber number of the sized fibers in vitro. Cytotoxicity was assessed by monitoring cytosolic lactate dehydrogenase release and loss of function as indicated by a decrease in zymosan-stimulated chemiluminescence. Results Microscopic analysis indicated that human alveolar macrophages completely engulfed glass fibers of the 20 μm length. All fiber length fractions tested exhibited equal cytotoxicity on a per fiber basis, i.e. increasing lactate dehydrogenase and decreasing chemiluminescence in the same concentration-dependent fashion. Conclusion The data suggest that due to the larger diameter of human alveolar macrophages, compared to rat alveolar macrophages, complete phagocytosis of longer fibers can occur with the human cells. Neither incomplete phagocytosis nor length-dependent toxicity was

  18. Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

    NARCIS (Netherlands)

    Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

    Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

  19. Cytotoxic effect of Erythroxylum suberosum combined with radiotherapy in head and neck cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Macedo, Taysa B.C.; Torres, Hianne M.; Yamamoto-Silva, Fernanda Paula; Silva, Maria Alves G. [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Escola de Odontologia; Elias, Silvia T.; Silveira, Damaris; Magalhaes, Perola O.; Lofrano-Porto, Adriana; Guerra, Eliete N.S., E-mail: elieteneves@unb.br [Universidade de Brasilia (UnB), Brasilia, DF (Brazil). Faculdade de Ciencias da Saude

    2016-01-15

    The mouth and oropharynx cancer is the 6{sup th} most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as 'cabelo-de-negro'. The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. (author)

  20. Cytotoxic Effect of Erythroxylum suberosum Combined with Radiotherapy in Head and Neck Cancer Cell Lines.

    Science.gov (United States)

    Macedo, Taysa B C; Elias, Silvia T; Torres, Hianne M; Yamamoto-Silva, Fernanda Paula; Silveira, Dâmaris; Magalhães, Pérola O; Lofrano-Porto, Adriana; Guerra, Eliete N S; Silva, Maria Alves G

    2016-01-01

    The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

  1. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells

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    Reem T. Attia

    2016-06-01

    Full Text Available Background. Glufosfamide (GLU is a glucose conjugate of ifosfamide in which isophosphoramide mustard is glycosidically linked to the β-D-glucose molecule. Based on GLU structure, it is considered a targeted chemotherapy with fewer side effects. The main objective of the current study is to assess the cytotoxic potential of GLU for the first time in prostate cancer (PC cells representing different stages of the tumor. Furthermore, this study examined the potential synergistic activity of GLU in combination with docetaxel (DOC. Methods. Two different cell lines were used, LNCaP and PC-3. Concentration-response curves were assessed. The tested groups per cell line were, control, GLU, DOC and combination. Treatment duration was 72 h. Cytotoxicity was assessed using sulforhodamine B (SRB assay and half maximal inhibitory concentration (IC50 was calculated. Synergy analyses were performed using Calcusyn®software. Subsequent mechanistic studies included β-glucosidase activity assay, glucose uptake and apoptosis studies, namely annexin V-FITC assay and the protein expression of mitochondrial pathway signals including Bcl-2, Bax, Caspase 9 and 3 were assessed. Data are presented as mean ± SD; comparisons were carried out using one way analysis of variance (ANOVA followed by Tukey-Kramer’s test for post hoc analysis. Results. GLU induced cytotoxicity in both cell lines in a concentration-dependent manner. The IC50 in PC-3 cells was significantly lower by 19% when compared to that of LNCaP cells. The IC50 of combining both drugs showed comparable effect to DOC in PC-3 but was tremendously lowered by 49% compared to the same group in LNCaP cell line. β-glucosidase activity was higher in LNCaP by about 67% compared to that determined in PC-3 cells while the glucose uptake in PC-3 cells was almost 2 folds that found in LNCaP cells. These results were directly correlated to the efficacy of GLU in each cell line. Treatment of PC cells with GLU as single

  2. Effects of organic extracts of six Bangladeshi plants on in vitro thrombolysis and cytotoxicity.

    Science.gov (United States)

    Rahman, M Atiar; Sultana, Rabeya; Bin Emran, Talha; Islam, M Saiful; Rahman, M Ashiqur; Chakma, Joti Sankhar; Rashid, Harun-ur; Hasan, Chowdhury Mohammad Monirul

    2013-01-30

    Thrombus formed in blood vessels lead to atherothrombotic diseases such as myocardial or cerebral infarction. Thrombolytic agents are used to dissolve the already formed clots in the blood vessels; however, these drugs sometimes cause serious and fatal consequences. Herbal preparations have been used since ancient times for the treatment of several diseases although they show little toxicity in some cases. Aqueous extracts of herbs used in thrombolysis have been reported before with cytotoxic data, however, the organic extracts of herbs have not been documented. This study aims to investigate whether organic extracts possess thrombolytic properties with minimal or no toxicity. An in vitro thrombolytic model was used to check the clot lysis effect of six Bangladeshi herbal extracts viz., Ageratum conyzoides L., Clausena suffruticosa, Leea indica (Burm.f.) Merr., Leucas aspera Willd., Senna sophera L. Roxb., and Solanum torvum Swartz. using streptokinase as a positive control and water as a negative control. Briefly, venous blood drawn from twenty healthy volunteers was allowed to form clots which were weighed and treated with the test plant materials to disrupt the clots. Weight of clot after and before treatment provided a percentage of clot lysis. Cytotoxicity was screened by brine shrimp lethality bioassay using vincristine sulfate as positive control. Using an in vitro thrombolytic model, Ageratum conyzoides, Clausena suffruticosa, Leea indica, Leucas aspera, Senna sophera and Solanum torvum showed 18.12 ± 2.34%, 48.9 ± 2.44%, 39.30 ± 0.96%, 37.32 ± 2.00%, 31.61 ± 2.97% and 31.51 ± 0.57% and clot lysis respectively. Among the herbs studied Clausena suffruticosa, Leea indica and Leucas aspera showed very significant (p Solanum torvum showed LC50 values 508.86 ± 6.62,41.16 ± 1.26, 2.65 ± 0.16, 181.67 ± 1.65, 233.37 ± 7.74 and 478.40 ± 3.23 μg/ml, respectively, with reference to vincristine sulfate (LC50 0.76 ± 0.04). Through our study it was found

  3. An In Vitro Assessment of Antimicrobial and Cytotoxic Effects of Nanosilver

    Directory of Open Access Journals (Sweden)

    Rokhsareh Sadeghi

    2015-10-01

    Full Text Available Background: The antimicrobial activity of silver nanoparticles has been investigated in medical fields in recent years, but there are few studies regarding its effect on oral microorganisms. The aim of the present study was to evaluate the in vitro antimicrobial and toxicity properties of nanosilver against two dental plaque microorganisms  and Human Gin- gival Fibroblast (HGF cell line.Methods: Antibacterial effects of nanosilver colloidal solution were de-termined by minimal inhibitory concentration (MIC and minimal bacte- ricidal   concentration   (MBC   using  microdilution   method.   Standard strains of Streptococcus sanguis and Actinomyces viscosus were used. For toxicity assessment,  MTT  and LDH  tests were performed  under  con- trolled conditions. Different concentrations of nanosilver were prepared and their toxic effects  on HGF were determined  after 24, 48 and 72 hours.Results: The MIC of nanosilver solution for S. sanguis and A. viscosuswere 16 and 4 µ g/ml, respectively. The MBC of nanosilver was 64 µ g/ml for S. sanguis and 16 µ g/ml for A. viscosus. MTT results showed that after 24 hours the concentrations of ≥ 0.5 µ g/ml of nanosilver solution affected cell viability when compared with control group. After 48 and 72 hours only the concentration of  ≥ 5 µ g/ml showed significant effect on cultured cell viability. LDH release test demonstrated toxic effect only after 48, 72 hours by 20 and 50 µ g/ml of nanosilver.Conclusion: The results demonstrated that beside its antibacterial activityagainst S. sanguis and A. viscosus, nanosilver mediated a concentration and time dependent cytotoxicity on HGF.

  4. Combinatorial cytotoxic effects of Curcuma longa and Zingiber officinale on the PC-3M prostate cancer cell line

    Science.gov (United States)

    Kurapati, Kesava Rao V.; Samikkannu, Thangavel; Kadiyala, Dakshayani B.; Zainulabedin, Saiyed M.; Gandhi, Nimisha; Sathaye, Sadhana S.; Indap, Manohar A.; Boukli, Nawal; Rodriguez, Jose W.; Nair, Madhavan P.N.

    2015-01-01

    Background Many plant-derived products exhibit potent chemopreventive activity against animal tumor models as well as rodent and human cancer cell lines. They have low side effects and toxicity and presumably modulate the factors that are critical for cell proliferation, differentiation, senescence and apoptosis. The present study investigates the effects of some medicinal plant extracts from generally recognized as safe plants that may be useful in the prevention and treatment of cancer. Methods Clonogenic assays using logarithmically-growing cells were performed to test the effect. The cytotoxic effects of Curcuma longa and Zingiber officinale were studied using sulforhodamine B assay, tetrazolium dye assay, colony morphology and microscopic analysis. Results Out of the 13 lyophilized plant-derived extracts evaluated for growth-inhibitory effects on the PC-3M prostate cancer cell line, two extracts derived from C. longa and Z. officinale showed significant inhibitory effects on colony-forming ability. The individual and augmentative effects of these two extracts were tested for their narrow range effective lower concentration on PC-3M in clonogenic assays. At relatively lower concentrations, C. longa showed significant inhibition of colony formation in clonogenic assays; whereas at same concentrations Z. officinale showed only moderate inhibitory effects. However, when both the agents were tested together at the same concentrations, the combined effects were much more significant than their individual ones. On normal prostate epithelial cells both C. longa and Z. officinale had similar effects but at a lower magnitude. These observations were confirmed by several cytotoxicity assays involving the morphological appearance of the colonies, microscopic observations, per cent inhibition in comparison to control by sulforhodamine B and tetrazolium dye assay. Conclusions From these observations, it was concluded that the combined effects of C. longa and Z. officinale

  5. Combinatorial cytotoxic effects of Curcuma longa and Zingiber officinale on the PC-3M prostate cancer cell line.

    Science.gov (United States)

    Kurapati, Kesava Rao V; Samikkannu, Thangavel; Kadiyala, Dakshayani B; Zainulabedin, Saiyed M; Gandhi, Nimisha; Sathaye, Sadhana S; Indap, Manohar A; Boukli, Nawal; Rodriguez, Jose W; Nair, Madhavan P N

    2012-01-01

    Many plant-derived products exhibit potent chemopreventive activity against animal tumor models as well as rodent and human cancer cell lines. They have low side effects and toxicity and presumably modulate the factors that are critical for cell proliferation, differentiation, senescence and apoptosis. The present study investigates the effects of some medicinal plant extracts from generally recognized as safe plants that may be useful in the prevention and treatment of cancer. Clonogenic assays using logarithmically-growing cells were performed to test the effect. The cytotoxic effects of Curcuma longa and Zingiber officinale were studied using sulforhodamine B assay, tetrazolium dye assay, colony morphology and microscopic analysis. Out of the 13 lyophilized plant-derived extracts evaluated for growth-inhibitory effects on the PC-3M prostate cancer cell line, two extracts derived from C. longa and Z. officinale showed significant inhibitory effects on colony-forming ability. The individual and augmentative effects of these two extracts were tested for their narrow range effective lower concentration on PC-3M in clonogenic assays. At relatively lower concentrations, C. longa showed significant inhibition of colony formation in clonogenic assays; whereas at same concentrations Z. officinale showed only moderate inhibitory effects. However, when both the agents were tested together at the same concentrations, the combined effects were much more significant than their individual ones. On normal prostate epithelial cells both C. longa and Z. officinale had similar effects but at a lower magnitude. These observations were confirmed by several cytotoxicity assays involving the morphological appearance of the colonies, microscopic observations, per cent inhibition in comparison to control by sulforhodamine B and tetrazolium dye assay. From these observations, it was concluded that the combined effects of C. longa and Z. officinale are much greater than their individual

  6. Evaluation of cytotoxic effect of photodynamic therapy in combination with electroporation in vitro

    DEFF Research Database (Denmark)

    Labanauskiene, J; Gehl, J; Didziapetriene, J

    2007-01-01

    . Thus, the aim of study was to evaluate the cytotoxic effect of PDT in combination with EP. A Chinese hamster lung fibroblast cell line (DC-3F) was used. The cells were affected by photosensitizers chlorin e(6) (C e(6)) at the dose of 10 mug/ml and aluminium phthalocyanine tetrasulfonate (AlPcS4...... tumor therapy (PDT)--the cancer treatment method based on the use of photosensitizers that localize selectively in malignant tumors and become cytotoxic when exposed to light, and EP, with the aim to enhance the delivery of photosensitizers into the tumor and therefore to increase the efficacy of PDT...... 14, emitted light from 660 nm). The fluence rate at the level of the cells was 3 mW/m(2). Cytotoxic effect on cells viability was evaluated using MTT assay. Our in vitro data showed that the cytotoxicity of PDT in combination with EP increases fourfold on the average. Based on the results we suggest...

  7. Antioxidant Activity and Cytotoxic Effect of Ventilago denticulata Willd Leaves Extracts.

    Science.gov (United States)

    Pongjanta, Anursara; Pangjit, Kanjana; Srichairatanakool, Somdet

    2016-01-01

    Oxidative stress is characterized by an imbalance between the antioxidant defense systems and the formation of reactive oxygen species (ROS). The excess of ROS can damage biomolecules and leading to several chronic conditions and diseases such as diabetes, antherosclerosis, ischemic injury, inflammation and carcinogenesis. Plant extracts and their constituents as a natural source of antioxidants have been extensively studied. The study aimed to investigate the antioxidant and cytotoxicity of aqueous and ethanolic Rhang Dang (entilago denticulata Willd) leaves extract. The aqueous and ethanolic extracts of Rhang Dang leaves were preliminary analyzed for their phenolic profile (total phenolics and total flavonoids). These extracts were evaluated for their antioxidant properties by different methods such as DPPH radical scavenging andperoxyl radical scavenging activity generated by AAPH (2,2'-Azobis (2-methylpropionamidine) dihydrochloride). Their cytotoxic effects on hepatocellular carcinoma cell line (HepG2) and peripheral blood mononuclear cells (PBMC) were determined by MTT assay. Anti-hemolytic activity was examined using spectrophotometrical method. The ethanolic extract from Rhang Dang leaves exhibited a strong antioxidant activity and prevented hemolysis. It showed the highest amount of phenolics (91.03 ± 12.43 mg of gallic acid equivalents/g extract) and flavonoid compound (69.76 ± 10.84 mg of catechin equivalents/g). Interestingly, this extract was more cytotoxic to HepG2 cells than PBMC. The ethanolic extract from Rhang Dang leaves had strong antioxidant activity and cytotoxic effect on cancer cells.

  8. Understanding the cytotoxicity or cytoprotective effects of biological and synthetic quinone derivatives by redox mechanism.

    Science.gov (United States)

    Borges, Rosivaldo S; Carneiro, Agnaldo S; Barros, Tainá G; Barros, Carlos A L; Neto, Antonio M J Chaves; da Silva, Albérico B F

    2014-12-01

    Quinones represent an important class of biological compounds, but are also involved with toxicological intermediates and among their hazardous effects include cytotoxicity, immunotoxicity, and carcinogenesis. The structure-toxicity relationship for quinone derivatives has been used to cytotoxicity or cytoprotective effects by redox mechanism is determined using quantum chemical calculations through the density functional theory (DFT). According to our DFT study, the electron acceptance is related with LUMO, electron affinity, and stabilization energy values. The highest spin density distribution in the heteroatoms is more favored for the more cytotoxic compounds. The electrophilic capacities of these compounds have been related with LUMO values. The cytotoxic properties of quinones are related to the stabilization energy after electron accepting by redox mechanism. Electron affinity is the most relevant parameter related to toxicity mechanism. Regioisomers has different electrophilic capacity. The electrophilicity increases on molecules containing electron-withdrawing groups (EWG) and reduces on molecules containing electron-donating groups (EDG). These results explain the toxic difference between natural and synthetic quinone derivatives and can be used in the design and study of new drugs.

  9. Fullerene C60 Penetration into Leukemic Cells and Its Photoinduced Cytotoxic Effects.

    Science.gov (United States)

    Franskevych, D; Palyvoda, K; Petukhov, D; Prylutska, S; Grynyuk, I; Schuetze, C; Drobot, L; Matyshevska, O; Ritter, U

    2017-12-01

    Fullerene C60 as a representative of carbon nanocompounds is suggested to be promising agent for application in photodynamic therapy due to its unique physicochemical properties. The goal of this study was to estimate the accumulation of fullerene C60 in leukemic cells and to investigate its phototoxic effect on parental and resistant to cisplatin leukemic cells. Stable homogeneous water colloid solution of pristine C60 with average 50-nm diameter of nanoparticles was used in experiments. Fluorescent labeled C60 was synthesized by covalent conjugation of C60 with rhodamine B isothiocyanate. The results of confocal microscopy showed that leukemic Jurkat cells could effectively uptake fullerene C60 from the medium. Light-emitting diode lamp (100 mW cm-2, λ = 420-700 nm) was used for excitation of accumulated C60. A time-dependent decrease of viability was detected when leukemic Jurkat cells were exposed to combined treatment with C60 and visible light. The cytotoxic effect of photoexcited C60 was comparable with that induced by H2O2, as both agents caused 50% decrease of cell viability at 24 h at concentrations about 50 μM. Using immunoblot analysis, protein phosphotyrosine levels in cells were estimated. Combined action of C60 and visible light was followed by decrease of cellular proteins phosphorylation on tyrosine residues though less intensive as compared with that induced by H2O2 or protein tyrosine kinase inhibitor staurosporine. All tested agents reduced phosphorylation of 55, 70, and 90 kDa proteins while total suppression of 26 kDa protein phosphorylation was specific only for photoexcited C60.The cytotoxic effect of C60 in combination with visible light irradiation was demonstrated also on leukemic L1210 cells both sensitive and resistant to cisplatin. It was shown that relative value of mitochondrial membrane potential measured with tetramethylrhodamine ethyl ester perchlorate (TMRE) probe was lower in resistant cells in comparison with

  10. Comparison of the TOX A/B test to a cell culture cytotoxicity assay for the detection of Clostridium difficile in stools.

    Science.gov (United States)

    Aldeen, W E; Bingham, M; Aiderzada, A; Kucera, J; Jense, S; Carroll, K C

    2000-04-01

    The TOX A/B Test (Techlab, Blacksburg, VA, USA) was compared to cell culture cytotoxicity assay on 1109 consecutive diarrheal stool samples collected from patients with the presumptive diagnosis of Clostridium difficile disease. The TOX A/B Test is an enzyme immunoassay in a microtiter format that detects both toxins A and B. The procedure used for this study takes approximately 1.5 h to perform. Cell culture cytotoxicity was performed by using a fibroblast cell line in a microtiter format read at 4 h, 24 h, and 48 h. One hundred ninety-four of the 1109 samples were positive by the "gold standard" cytotoxicity assay, whereas 189 were positive by EIA. There was a 98.5% agreement between the two assays. When compared to the cytotoxicity assay, the EIA had an initial sensitivity of 94.3% and a specificity of 99.3%. However, after resolution of six discrepants using another ELISA for toxin A detection the sensitivity, specificity, positive and negative predictive values for the TOX A/B test are as follows: 94.5%; 100%; 100%; 98.8%. The corresponding values for the cytotoxicity assay are: 97%; 100%; 100%; and 99.3%. This test seems to have excellent sensitivity and specificity as compared to an in-house cell culture cytotoxicity assay. It is sensitive enough to use as a stand-alone test for the detection of C. difficile toxin in laboratories that do not have cell culture cytotoxicity testing capability.

  11. Cytotoxic and genotoxic effects of aqueous extracts of five medicinal plants on Allium cepa Linn.

    Science.gov (United States)

    Akinboro, A; Bakare, A A

    2007-07-25

    The cytotoxic and genotoxic effects of aqueous extracts of five medicinal plants: Azadirachta indica (A. Juss), Morinda lucida (Benth.), Cymbopogon citratus (DC Stapf.), Mangifera indica (Linn.) and Carica papaya (Linn.) was evaluated using the Allium cepa assay. The extracts were prepared with tap water as practised locally. Onion bulbs were exposed to 1, 5, 10, 25 and 50%; and 1, 2.5, 5, 10 and 20% concentrations (v/v) of each of the extracts for macroscopic and microscopic analyses, respectively. There was concentration-dependent and statistically significant (P<0.05) inhibition of root growth by the extracts when compared with the control. The EC(50) obtained for decoctions of Azadirachta indica. Cymbopogon citratus, Mangifera indica and Carica papaya were 0.6, 3.0, 1.4 and 0.8%, respectively. It was 2.6 and 0.8% for the squeezed extracts of Azadirachta indica and Morinda lucida, respectively. All the tested extracts were observed to have mitodepressive effects on cell division and induced mitotic spindle disturbance in Allium cepa. These results suggest an inhibitory, mitodepressive and turbagenic activities of the aqueous extracts on Allium cepa.

  12. Antioxidant, antibacterial and cytotoxic effects of the phytochemicals of whole Leucas aspera extract.

    Science.gov (United States)

    Rahman, Md Atiar; Islam, Md Saiful

    2013-04-01

    To investigate the antioxidant, antibacterial and cytotoxic activity of whole Leucas aspera (Labiatae) (L. aspera) alcoholic extract. Whole L. aspera powder was extracted by absolute ethanol (99.50%). The ethanolic extract was subjected to antioxidant, antibacterial and brine shrimp lethality assay. The extract showed potent radical scavenging effect (antioxidant) with IC50 value of (99.58±1.22) µg/mL which was significant (Pscreening, the extract showed notable antibacterial effect against the tested microbial strains. Significant (P<0.05) zone of inhibitions against Gram positive Bacillus subtilis [(12.00±1.32) mm] and Bacillus megaterium [(13.00±1.50) mm], Staphylococcus aureus [(8.00±0.50) mm] and Gram negative Salmonella typhi [(6.00±0.50) mm], Salmonella paratyphi [(8.00±1.00) mm], Shigella dysenteriae [(9.00±1.32) mm] and Vibrio cholerae [(9.00±0.66) mm] was observed. In brine shrimp lethality bioassay, the extract showed the LC50 value as (181.68±2.15) µg/mL which was statistically significant (P<0.01) compared to positive control vincristine sulfate [LC50=(0.76±0.04) µg/mL]. The results demonstrate that the ethanolic extract of L. aspera could be used as antibacterial, pesticidal and various pharmacologic actives.

  13. Assessment of antibacterial and cytotoxic effects of orthodontic stainless steel brackets coated with different phases of titanium oxide: An in-vitro study.

    Science.gov (United States)

    Baby, Roshen Daniel; Subramaniam, Siva; Arumugam, Ilakkiya; Padmanabhan, Sridevi

    2017-04-01

    Our objective was to assess the antibacterial and cytotoxic effects of orthodontic stainless steel brackets coated with different phases of photocatalytic titanium oxide. From a total sample of 115 brackets, 68 orthodontic stainless steel brackets were coated with titanium oxide using a radiofrequency magnetron sputtering machine. The coated brackets were then converted into 34 each of the anatase and rutile phases of titanium oxide. These brackets were subdivided into 4 groups for antibacterial study and 3 groups for cytotoxicity study. Brackets for the antibacterial study were assessed against the Streptococcus mutans species using microbiologic tests. Three groups for the cytotoxicity study were assessed using the thiazolyl tetrazolium bromide assay. The antibacterial study showed that both phases were effective, but the rutile phase of photocatalytic titanium oxide had a greater bactericidal effect than did the anatase phase. The cytotoxicity study showed that the rutile phase had a greater decrease in viability of cells compared with the anatase phase. It is recommended that orthodontic brackets be coated with the anatase phase of titanium oxide since they exhibited a significant antibacterial property and were only slightly cytotoxic. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  14. Augmentation of the cytotoxic effects of zinc oxide nanoparticles by MTCP conjugation: Non-canonical apoptosis and autophagy induction in human adenocarcinoma breast cancer cell lines.

    Science.gov (United States)

    Mozdoori, Najmeh; Safarian, Shahrokh; Sheibani, Nader

    2017-09-01

    Zinc oxide nanoparticles are very toxic, but their agglomeration reduces their lethal cytotoxic effects. Here we tested the hypothesis that conjugation of ZnO nanoparticles via Meso-Tetra (4-Carboxyphenyl) Porphyrin (MTCP) could provide electrostatic or steric stabilization of ZnO nanoparticles and increase their cytotoxic effects. The cytotoxicity and cell death induction were assessed using two human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-468). The MTT results indicated that the toxicity of ZnO nanoparticles was significantly increased upon MTCP conjugation. Annexin/PI and real time RT-PCR results demonstrated that the ZnO-MTCP nanoparticles induced cell death via different non-canonical pathways that are under ca2+ control. Calcium signaling could regulate lysosomal dependent apoptosis and death autophagy, and killing of the two selected types of breast cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The cytotoxic and embryotoxic effects of kaurenoic acid, a diterpene isolated from Copaifera langsdorffii oleo-resin.

    Science.gov (United States)

    Costa-Lotufo, L V; Cunha, G M A; Farias, P A M; Viana, G S B; Cunha, K M A; Pessoa, C; Moraes, M O; Silveira, E R; Gramosa, N V; Rao, V S N

    2002-08-01

    In this work, we studied the effects of kaurenoic acid, a diterpene isolated from the oleo-resin of Copaifera langsdorffii in developing sea urchin (Lytechinus variegatus) embryos, on tumor cell growth in microculture tetrazolium (MTT) test and on mouse and human erythrocytes in hemolysis assay. Continuous exposure of embryos to kaurenoic acid starting immediately after fertilization inhibited the first cleavage (IC(50): 84.2 microM) and progressively induced embryo destruction (IC(50): 44.7 microM and sea urchin embryos, the inhibition of tumor cell growth and the hemolysis of mouse and human erythrocytes indicate the potential cytotoxicity of kaurenoic acid.

  16. Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin.

    Science.gov (United States)

    Domínguez-Gómez, G; Díaz-Chávez, J; Chávez-Blanco, A; Gonzalez-Fierro, A; Jiménez-Salazar, J E; Damián-Matsumura, P; Gómez-Quiroz, L E; Dueñas-González, A

    2015-02-01

    Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1‑ and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1‑deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild‑type MDA-MB-231 cells, to demonstrate its effects as a chemo‑ or radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo‑ and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo‑ or radiosensitizing agent regardless of the BRCA1 status in breast cancer.

  17. Cytotoxic, antitumour-promoting and inhibition of protein denaturation effects of flavonoids, isolated from Potentilla evestita Th. Wolf.

    Science.gov (United States)

    Rauf, Abdur; Khan, Rehan; Khan, Haroon; Tokuda, Harukuni

    2015-01-01

    This study was designed to evaluate the isolated flavonoids (chrysin 1, and umbelliferone 2) from Potentilla evestita for cytotoxic, antitumour-promoting and inhibition of protein denaturation activities. The results showed marked cytotoxic effect of compounds 1 and 2 in brine shrimp cytotoxic assay at various concentrations with LD50 of 34.5 and 31.8 mg/mL, respectively. In Epstein-Barr-virus early antigen activation assay, both compounds 1 and 2 illustrated significant antitumour-promoting effect with IC50 values of 462 and 308 mol ratio/32 pmol TPA, respectively. The cytotoxic and antitumour-promoting effects of compounds were strongly supported by inhibition of protein denaturation activity with IC50 of 119 and 112 μg/mL, respectively. In conclusion, both compounds possess strong cytotoxic, antitumour-promoting and inhibition of protein denaturation activities.

  18. Cytotoxic effects of etephon and maleic hydrazide in Vero, Hep2, HepG2 cells.

    Science.gov (United States)

    Yurdakok, Begum; Baydan, Emine; Okur, Hamza; Gurcan, Ismayil Safa

    2014-10-01

    The toxicity of etephon and maleic hydrazide, used as plant growth regulators in agriculture, were reported as low in mammals in previous studies. However, in vitro cytotoxicity studies in mammalian cells are currently missing to understand their toxicity at molecular level. In the current study, the cytotoxicity of these compounds, were studied in Vero (African green monkey kidney epithelium), HepG2 (human hepatocellular carcinoma), Hep2 (human epidermoid cancer) cells by MTT ((3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromure) and LDH (lactate dehydrogenase) assays. Maleic hydrazide had lower IC50 values for all cell lines compared to ethephon. Least cytotoxic effect treated by ethephon were observed in Vero, followed by HepG2 and Hep2. Similarly maleic hydrazide also showed least cytotoxicity on Vero cells, followed by Hep2 and HepG2 cells (p Vero cells, followed by HepG2 and Hep2 cells (p 0.868 (p cells to be supplemented by further studies.

  19. In vitro combined cytotoxic effects of pesticide cocktails simultaneously found in the French diet.

    Science.gov (United States)

    Takakura, Natsuko; Sanders, Pascal; Fessard, Valérie; Le Hégarat, Ludovic

    2013-02-01

    Although human populations may be constantly exposed to complex pesticide mixtures through their diet, the human health risk of pesticide exposure is currently assessed on the basis of toxicity data on individual compounds. To investigate the combined toxic effects of pesticide cocktails previously identified in the French diet, we first studied the cytotoxicity induced by seven cocktails composed of two to six pesticides on human hepatic (HepG2) and colon (Caco-2) cell lines using the MTT and neutral red uptake assays. Secondly, we challenged to assess the combined effects of the two most cytotoxic cocktails by comparing the measured effects of the mixtures with the predictions based on additive effects on two concepts-independent action (IA) and concentration addition (CA). For the cocktail composed of dichlorodiphenyltrichloroethane (DDT) and dieldrin, the cytotoxicity of the equimolar cocktail proved greater than the additive effect estimated by the two concepts. Furthermore, apoptosis induction was higher in equimolar cocktail than predicted by summing the effects of DDT and dieldrin. Thus, some supra-additive toxicity was found in the DDT-dieldrin cocktail. Nevertheless, if IA and CA models could reveal combined effects of pesticide cocktails, an accurate evaluation remains challenging. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Additive cytotoxic effects of radiation and mTOR inhibitors in a cervical cancer cell line.

    Science.gov (United States)

    Assad, Daniele Xavier; Borges, Gabriel Alvares; Avelino, Samuel Ramalho; Guerra, Eliete Neves Silva

    2018-02-01

    The PI3K/AKT/mTOR signaling pathway is frequently activated in HPV-positive cervical squamous cell cancer (CC). This study investigated the biological effects of mTOR inhibitors associated with radiotherapy in a CC cell line (HeLa). A human keratinocyte cell line (HaCaT) was used as control. Temsirolimus, everolimus, resveratrol, curcumin and epigallocatechin gallate (EGCG) were the mTOR inhibitors assessed. The 50% cell cytotoxicity rate (CC 50 ) for each treatment was determined by MTT cell viability assay. Cells were pre-treated with mTOR inhibitors at CC 50 followed by radiotherapy (RT) at 2Gy. Cell death profile after treatment with temsirolimus, resveratrol and curcumin was assessed with flow cytometry. Everolimus, temsirolimus, EGCG, resveratrol and curcumin were cytotoxic to HeLa. Radiation induced a statistically significant (p<0.01) supra-additive cytotoxic effect in the cervical cancer cell line when combined with mTOR inhibitors. After a 24-h treatment, EGCG and resveratrol were more cytotoxic to HeLa cells than to HaCaT cells. After 48h of treatment, resveratrol, curcumin and everolimus were more cytotoxic to HeLa cells when compared to HaCaT cells. After 24h, temsirolimus induced late apoptosis or necrosis in HeLa cells. Based on these data, new studies with mTOR inhibitors as treatment options for cervical cancer are recommended, mainly combined to radiotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Cheminformatics based selection and cytotoxic effects of herbal extracts.

    OpenAIRE

    Sardari, Soroush; Shokrgozar, Mohammad Ali; Ghavami, Ghazaleh

    2009-01-01

    International audience; Bioinformatics and traditional medicine can be used in discovery and design of novel candidate drugs to efficient cancer chemotherapy. In this study, similarity search tools employed to screen and introduce novel herbs with antitumor property. Several novel herbs have been selected by using logical computational algorithms and assayed on six cancerous cell lines. Complementary assays involved hemolytic and antifungal MIC tests have been performed to determine selectivi...

  2. Differential cytotoxic effects on odontoblastic cells induced by self-adhesive resin cements as a function of the activation protocol.

    Science.gov (United States)

    D'Alpino, Paulo Henrique Perlatti; Moura, Gioconda Emanuella Diniz de Dantas; Barbosa, Silvana Coelho de Arruda; Marques, Lygia de Azevedo; Eberlin, Marcos Nogueira; Nascimento, Fábio Dupart; Tersariol, Ivarne Luis Dos Santos

    2017-12-01

    To evaluate the cytotoxic effects of exposing odontoblast cells to a variety of commercial self-adhesive cements polymerized using different activation modes. Five cements: MaxCem Elite (MAX), Bifix SE (BSE), G-Cem LinkAce (GCE), Clearfil SA Luting (CAS), and RelyX U200 (U200) were mixed, dispensed into molds, and distributed in groups, according to polymerization protocols: immediate photoactivation; delayed photoactivation (10min self-curing plus light-activation); and chemical activation (no light exposure). Immortalized rat odontoblast cells (MDPC-23) were cultured. Cell viability was assessed by Trypan Blue staining and total cell death was assessed by annexin V-APC/7-AAD double staining and flow cytometry. Volatilized compounds from polymerized specimens of cements were evaluated by gas chromatography/mass spectrometry (GC-MS). Data was analyzed with 2-way ANOVA/Tukey tests (α=0.05). Exposure to all of the cements tested significantly reduced the cell viability, irrespective of the activation protocol (pcements were CSA and U200. Total death of cells significantly increased when exposed to BSE, GCE, and MAX, especially when chemically activated (pcements, mainly for MAX, regardless of the activation mode. Chemical activation of MAX also induced necrosis. Moreover, GCE and MAX exhibited higher percentages of late apoptotic/dead cells. Chromatograms revealed 28 compounds released from the cements tested, some of them with known carcinogenic effects. Selection of self-adhesive cements and polymerization protocols affect the cytotoxicity and cell viability of odontoblastic cells. Despite the simplified cementation protocol, care is needed when cementing indirect restorations with self-adhesive cements, especially on recently exposed dentin. This category of material may cause differential cytotoxic effects and should be considered when selecting a cement. This is particularly true in clinical cases of light attenuation, where the polymerization depends on

  3. Evaluation of cytotoxic effects of several novel tetralin derivatives against Hela, MDA-MB-468, and MCF-7 cancer cells

    Directory of Open Access Journals (Sweden)

    Fateme Shafiee

    2012-01-01

    Conclusion: With the exception of compound 2, other tested compounds have potential for further cytotoxicity evaluation. Synthesizing other tetralin derivatives similar to compound 4 and studying their structure-activity relationships (SARs would be encouraged.

  4. Evaluation of anticancer effects and enhanced doxorubicin cytotoxicity of xanthine derivatives using canine hemangiosarcoma cell lines.

    Science.gov (United States)

    Motegi, Tomoki; Katayama, Masaaki; Uzuka, Yuji; Okamura, Yasuhiko

    2013-10-01

    Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac, and central nervous system stimulatory effects. Moreover, caffeine inhibits the development of tumors induced by various carcinogens. The aim of this work was to elucidate the anticancer effects on apoptosis of xanthine derivatives alone and with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or without doxorubicin were administered to cells, and the effects were investigated by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and theophylline induced apoptosis, and the treated cells expressed annexin V and caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however, hypoxanthine showed no effect. These results indicate that theophylline is similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have anticancer effects and can improve the treatment effect in canine hemangiosarcoma patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Green synthesis of silver nanoparticles and investigation of their colorimetric sensing and cytotoxicity effects

    Science.gov (United States)

    Pahlavan Noghabi, Mohammad; Parizadeh, Mohammad Reza; Ghayour-Mobarhan, Majid; Taherzadeh, Danial; Hosseini, Hasan Ali; Darroudi, Majid

    2017-10-01

    The ;Green; synthesis of metallic nanoparticles and investigation of their optical properties has become a useful application between nanoscience and medicine. In this work, silver nanoparticles (Ag-NPs) were successfully prepared through a facile and green method by treating silver ions with chitosan. Preparation of Ag-NPs in silver nitrate solution (0.01 M) resulted in small and spherical shapes of Ag-NPs with a mean diameter of 10.2 nm. The formation of Ag-NPs was approved by surface Plasmon resonance (SPR) absorption peaks, using UV-vis spectrophotometer, while Ag-NPs were successfully employed in colorimetric sensing of H2O2 via an analytical procedure. Degradation process of Ag-NPs, encouraged by the catalytic decomposition of H2O2, causes a significant change in the absorbance intensity of SPR band depending on the H2O2 concentration. The cytotoxicity effect of synthesized Ag-NPs was examined on HEK293 cell line. The results illustrate a concentration-dependent toxicity for the tested cells, while15.07 μg/mL of IC50 was obtained.

  6. Cytotoxicity of Carbon Nanotubes on J774 Macrophages Is a Purification-Dependent Effect

    Directory of Open Access Journals (Sweden)

    Silvia Lorena Montes-Fonseca

    2012-01-01

    Full Text Available The cytotoxicity of the carbon nanotubes (CNTs is an important factor for the manufacture of nanovaccines. The aim of this work was to evaluate the relationship of the purification method of CNTs in cellular toxicity using macrophages (MOs from the J774 cell line. Viability test was performed with MTT assays at 24 h of exposure at concentrations of 0.06, 0.6, and 6 mg/L of unpurified (UP-CNTs or purified (P-CNTs CNTs by two different methods: (1 reflux with 3M HNO3 and (2 sonication in H2SO4/HNO3. Characterization and COOH content of CNTs was performed using scanning electron microscopy, raman spectroscopy, and titration with NaHCO3. P-CNTs1 had lengths >100 μm and 2.76% COOH content, while P-CNTs2 had lengths >1 μm and 7% COOH content. This last particle showed a lower toxic effect. The results suggest that the lenght and COOH content are important factors in the toxicity of the CNTs.

  7. Evaluation of Cytotoxic and Antimicrobial Effects of Two Bt Cry Proteins on a GMO Safety Perspective

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    Davi Felipe Farias

    2014-01-01

    Full Text Available Studies have contested the innocuousness of Bacillus thuringiensis (Bt Cry proteins to mammalian cells as well as to mammals microbiota. Thus, this study aimed to evaluate the cytotoxic and antimicrobial effects of two Cry proteins, Cry8Ka5 (a novel mutant protein and Cry1Ac (a widely distributed protein in GM crops. Evaluation of cyto- and genotoxicity in human lymphocytes was performed as well as hemolytic activity coupled with cellular membrane topography analysis in mammal erythrocytes. Effects of Cry8Ka5 and Cry1Ac upon Artemia sp. nauplii and upon bacteria and yeast growth were assessed. The toxins caused no significant effects on the viability (IC50>1,000 µg/mL or to the cellular DNA integrity of lymphocytes (no effects at 1,000 µg/mL. The Cry8Ka5 and Cry1Ac proteins did not cause severe damage to erythrocytes, neither with hemolysis (IC50>1,000 µg/mL nor with alterations in the membrane. Likewise, the Cry8Ka5 and Cry1Ac proteins presented high LC50 (755.11 and >1,000 µg/mL, resp. on the brine shrimp lethality assay and showed no growth inhibition of the microorganisms tested (MIC>1,000 µg/mL. This study contributed with valuable information on the effects of Cry8Ka5 and Cry1Ac proteins on nontarget organisms, which reinforce their potential for safe biotechnological applications.

  8. Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Chueh, Pin Ju [Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan (China); Graduate Institute of Basic Medicine, China Medical University, Taichung 40402, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan (China); Department of Biotechnology, Asia University, Taichung 41354, Taiwan (China); Liang, Ruei-Yue; Lee, Yi-Hui; Zeng, Zih-Ming [Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan (China); Chuang, Show-Mei, E-mail: smchuang@dragon.nchu.edu.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan (China)

    2014-01-15

    Highlights: • AuNPs induce apoptosis in Vero cells. • AuNPs-induced attenuation of cell growth in NIH3T3 cells through autophagy. • Cell-cycle delay was associated with the resistance to AuNPs in MRC-5 cells. • Cell growth was continuously monitored using the measurement of cell impedance. -- Abstract: Gold nanoparticles (AuNPs) possess unique properties that have been exploited in several medical applications. However, a more comprehensive understanding of the environmental safety of AuNPs is imperative for use of these nanomaterials. Here, we describe the impacts of AuNPs in various mammalian cell models using an automatic and dye-free method for continuous monitoring of cell growth based on the measurement of cell impedance. Several well-established cytotoxicity assays were also used for comparison. AuNPs induced a concentration-dependent decrease in cell growth. This inhibitory effect was associated with apoptosis induction in Vero cells but not in MRC-5 or NIH3T3 cells. Interestingly, cDNA microarray analyses in MRC-5 cells supported the involvement of DNA damage and repair responses, cell-cycle regulation, and oxidative stress in AuNP-induced cytotoxicity and genotoxicity. Moreover, autophagy appeared to play a role in AuNPs-induced attenuation of cell growth in NIH3T3 cells. In this study, we present a comprehensive overview of AuNP-induced cytotoxicity in a variety of mammalian cell lines, comparing several cytotoxicity assays. Collectively, these assays offer convincing evidence of the cytotoxicity of AuNPs and support the value of a systematic approach for analyzing the toxicology of nanoparticles.

  9. Effect of Boiling on the Cytotoxic and Antioxidant Properties of ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of boiling on in vitro bioactivities potency of Balanites aegyptiaca L. Delile (desert date) aqueous extract, a juice used traditionally for cooking ready-to-eat millet flour paste. Methods: Desert date fruits (1.5 kg) were soaked in water (1:2, fruit: water) for 24 h and sieved. The extract was divided ...

  10. Cytotoxic Effect of Crude Aqueous Extract of Pistia Stratiotes Leaves ...

    African Journals Online (AJOL)

    Pistia stratiotes is a medicinal plant used traditionally to treat a various diseases such as skin infections, worm infections, tuberculosis, ulcer, diabetes etc. The present study was designed to investigate the effect this crude aqueous extract may have on body weight and renal cells function in albino rats. Twelve white Albino ...

  11. Cytotoxic effects of gold nanoparticles: a multiparametric study.

    Science.gov (United States)

    Soenen, Stefaan J; Manshian, Bella; Montenegro, José Maria; Amin, Faheem; Meermann, Björn; Thiron, Toke; Cornelissen, Maria; Vanhaecke, Frank; Doak, Shareen; Parak, Wolfgang J; De Smedt, Stefaan; Braeckmans, Kevin

    2012-07-24

    The in vitro labeling of therapeutic cells with nanoparticles (NPs) is becoming more and more common, but concerns about the possible effects of the NPs on the cultured cells are also increasing. In the present work, we evaluate the effects of poly(methacrylic acid)-coated 4 nm diameter Au NPs on a variety of sensitive and therapeutically interesting cell types (C17.2 neural progenitor cells, human umbilical vein endothelial cells, and PC12 rat pheochromocytoma cells) using a multiparametric approach. Using various NP concentrations and incubation times, we performed a stepwise analysis of the NP effects on cell viability, reactive oxygen species, cell morphology, cytoskeleton architecture, and cell functionality. The data show that higher NP concentrations (200 nM) reduce cell viability mostly through induction of reactive oxygen species, which was significantly induced at concentrations of 50 nM Au NPs or higher. At these concentrations, both actin and tubulin cytoskeleton were deformed and resulted in reduced cell proliferation and cellular differentiation. In terms of cell functionality, the NPs significantly impeded neurite outgrowth of PC12 cells up to 20 nM concentrations. At 10 nM, no significant effects on any cellular parameter could be observed. These data highlight the importance of using multiple assays to cover the broad spectrum of cell-NP interactions and to determine safe NP concentrations and put forward the described protocol as a possible template for future cell-NP interaction studies under comparable and standardized conditions.

  12. Carnosine's effect on amyloid fibril formation and induced cytotoxicity of lysozyme.

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    Josephine W Wu

    Full Text Available Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases.

  13. Studying the effect of physically-adsorbed coating polymers on the cytotoxic activity of optimized bisdemethoxycurcumin loaded-PLGA nanoparticles.

    Science.gov (United States)

    Mehanny, Mina; Hathout, Rania M; Geneidi, Ahmed S; Mansour, Samar

    2017-05-01

    The aim of this work was to study the effect of different physically-adsorbed coating polymers on the cytotoxic activity of optimized bisdemethoxycurcumin (BDMC) loaded-PLGA nanoparticles. BDMC-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles were prepared adopting the nanoprecipitation technique according to a full factorial study design. The effects of three independent variables each at two levels, namely: the polymer type, polymer concentration, and poly vinyl alcohol concentration were studied. The particles were optimized regarding particle size and entrapment efficiency where sizes coating using various coating moieties, namely: PEG 4000, Tween 80 and Pluronic F68, to impart a hydrophilic stealth character to the surface. The surface hydrophobicity was assessed using the Rose Bengal dye test where the hydrophilicity character followed the following order: Tween 80 > PEG 4000 > Pluronic F68. The particles coating rendered the particles suitable for cancer-targeting regarding particle size measurements, morphology, release kinetics, and stability studies. Moreover, cytotoxicity testing was performed using HepG-2 cells. Coated NPs showed the highest inhibition of malignant cells viability compared to the uncoated NPs and free BDMC where the IC 50 of Pluronic-F68 coated NPs was 0.54 ± 0.01 µg/mL. The augmented effect against malignant cells poses these particles as a successful cancer remedy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1433-1445, 2017. © 2017 Wiley Periodicals, Inc.

  14. Differential toxicity of Disperse Red 1 and Disperse Red 13 in the Ames test, HepG2 cytotoxicity assay, and Daphnia acute toxicity test.

    Science.gov (United States)

    Ferraz, E R A; Umbuzeiro, G A; de-Almeida, G; Caloto-Oliveira, A; Chequer, F M D; Zanoni, M V B; Dorta, D J; Oliveira, D P

    2011-10-01

    Azo dyes are of environmental concern due to their degradation products, widespread use, and low-removal rate during conventional treatment. Their toxic properties are related to the nature and position of the substituents with respect to the aromatic rings and amino nitrogen atom. The dyes Disperse Red 1 and Disperse Red 13 were tested for Salmonella mutagenicity, cell viability by annexin V, and propidium iodide in HepG2 and by aquatic toxicity assays using daphnids. Both dyes tested positive in the Salmonella assay, and the suggestion was made that these compounds induce mainly frame-shift mutations and that the enzymes nitroreductase and O-acetyltransferase play an important role in the observed effect. In addition, it was shown that the presence of the chlorine substituent in Disperse Red 13 decreased the mutagenicity about 14 times when compared with Disperse Red 1, which shows the same structure as Disperse Red 13, but without the chlorine substituent. The presence of this substituent did not cause cytotoxicity in HepG2 cells, but toxicity to the water flea Daphnia similis increased in the presence of the chlorine substituent. These data suggest that the insertion of a chlorine substituent could be an alternative in the design of dyes with low-mutagenic potency, although the ecotoxicity should be carefully evaluated. Copyright © 2010 Wiley Periodicals, Inc.

  15. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines

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    Yerly Vargas Casanova

    2017-09-01

    Full Text Available Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922 and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

  16. Azithromycin: assessment of intrinsic cytotoxic effects on corneal epithelial cell cultures

    Directory of Open Access Journals (Sweden)

    Mencucci R

    2013-05-01

    Full Text Available Rita Mencucci,1 Domenico E Pellegrini-Giampietro,2 Iacopo Paladini,1 Eleonora Favuzza,1 Ugo Menchini,1 Tania Scartabelli21Department of Specialized Surgical Science – Eye Clinic, 2Department of Health Science Section of Clinical Pharmacology and Oncology, University of Florence, Florence, ItalyPurpose: To compare the cytotoxic effects of preservative-free azithromycin on corneal epithelial cells in vivo with those of preservative-free netilmicin and levofloxacin, and the preservative benzalkonium chloride (BAK.Methods: Rabbit corneal epithelial cells in vitro were incubated for 15 minutes or 6 hours with commercially available ophthalmic preservative-free netilmicin 0.3%, levofloxacin 0.3%, or azithromycin 1.5% preparations or different concentrations of unpreserved azithromycin and different concentrations of BAK. Qualitative analysis was undertaken using phase-contrast optics to examine the morphological aspects of cell cultures and quantitative analysis was undertaken by measuring the release of the cytoplasmic enzyme lactate dehydrogenase into the medium immediately and 24 hours after exposure to drugs. Finally, we observed the wound-healing rate of mechanically injured corneal epithelial cells exposed to each antibiotic ophthalmic preparation for 48 hours.Results: Our results show that both the commercially available unpreserved mono-dose preparation of azithromycin and ophthalmic preparations of azithromycin up to a concentration of 1.5% were virtually devoid of harmful effects under our experimental conditions. This was not significantly different from the results obtained for the other antibiotic preparations (P > 0.05 tested, but was unlike the results obtained for BAK. Azithromycin 1.5% also showed good recovery properties after a mechanical wound test.Conclusion: Under our experimental conditions, unpreserved azithromycin 1.5% showed a much lower toxicity than BAK and did not interfere with the wound-healing process

  17. In vitro assessment of the genotoxic and cytotoxic effects of boiled juice (tucupi) from Manihot esculenta Crantz roots.

    Science.gov (United States)

    Cunha, L A; Mota, T C; Cardoso, P C S; Alcântara, D D F Á; Burbano, R M R; Guimarães, A C; Khayat, A S; Rocha, C A M; Bahia, M O

    2016-10-05

    The population of Pará (a state in Brazil) has a very characteristic food culture, as a majority of the carbohydrates consumed are obtained from cassava (Manihot esculenta Crantz) derivatives. Tucupi is the boiled juice of cassava roots that plays a major role in the culinary footprint of Pará. Before boiling, this juice is known as manipueira and contains linamarin, a toxic glycoside that can decompose to hydrogen cyanide. In this study, the cytotoxic and genotoxic effects of tucupi on cultured human lymphocytes were assessed using the comet assay and detection of apoptosis and necrosis by differential fluorescent staining with acridine orange-ethidium bromide. Tucupi concentrations (v/v) were determined using the methylthiazole tetrazolium biochemical test. Concentrations of tucupi that presented no genotoxic effects (2, 4, 8, and 16%) were used in our experiments. The results showed that under our study conditions, tucupi exerted no genotoxic effects; however, cytotoxic effects were observed with cell death mainly induced by necrosis. These effects may be related to the presence of hydrogen cyanide in the juice.

  18. The effects of accelerated electrons on Escherichia Coli enterobacteria cytotoxic activity

    Science.gov (United States)

    Oproiu, C.; Martin, D.; Marghitu, S.; Popescu, A. S.; Butan, C.; Toma, M.; Hategan, A.; Dima, V.

    1999-01-01

    Electron beam effects of the cytotoxic capacity of enterotoxin Escherichia coli on “in vitro” cell colonies have been studied. The VERO cell colonies and tumoral epithelial cells HeLa-2 were treated with different concentrations of irradiated and natural entherotoxin (1-1000 μg/mL). The radiation doses used range from 1 to 35 kGy. The irradiation was carried out with ALIN-10 linear accelerator and the dose was measured with calorimetric devices and cellulose triacetate dosimetric films. The accelerated electrons effects were estimated by means of the effect of different absorbed radiation doses on the enterotoxin and on the protein synthesis in cell colonies treated with irradiated enterotoxin. The following results were obtained: a) there is a definite dependence between the electron beam irradiation and effects on cytotoxic activity of the enterotoxin; b) strong inhibition of protein synthesis is produced in cell colonies treated with large amounts of enterotoxin; c) the cytotoxic activity of treated enterotoxin with 35 kGy accelerated electrons is fully suppressed; d) the VERO cells are more sensitive against natural and irradiated enterotoxin, as compared with tumoral epithelial cells HeLa-2.

  19. Pharmacologic modification of the cytotoxic effects of cadmium in LLC-PK sub 1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Battaglia, D.R.; Kahan, B.S.; Niewenhuis, R.J.; Prozialeck, W.C. (Philadelphia College of Osteopathic Medicine, PA (USA))

    1989-02-09

    Recent results from our laboratories have shown that exposure to cadmium causes LLC-PK{sub 1} cells to shrink, detach and assume a spherical shape. The purpose of the present studies was to determine whether various pharmacologic agents can reduce or prevent these cytotoxic effects of Cd{sup 2+}. Confluent monolayers of LLC-PK{sub 1} cells were incubated with the drugs of interest (50 microM final concentration) for 2 hours. CadCl{sub 2} (final concentration = 75 microM) was then added and the cells were incubated for another 20 hours. Morphologic changes were assessed qualitatively by viewing the cells with a phase contrast microscope. The extent of Cd{sup 2+}-induced cellular damage was also quantified by staining the cells that remained on the growing surface with methylene blue, solubilizing the stained cells, and determining the absorbance at 660 nm. The results showed that several drugs, particularly the calmodulin antagonists trifluoperazine chlorpromazine, and the calcium channel blocker verapamil, significant reduced the severity of Cd{sup 2+}-induced cytotoxicity. By contrast, a variety of other agents, such as chlorpromazine sulfoxide, trifluoperazine sulfoxide, phenytoin and zinc, had no such protective effect. These findings indicate that Ca{sup 2+} antagonists can attenuate the cytotoxic effects of Cd{sup 2+} and that Cd{sup 2+} may produce some of its effects by activating Ca{sup 2+} -dependent systems.

  20. Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells.

    Directory of Open Access Journals (Sweden)

    Ana M Sanchez-Sanchez

    Full Text Available Melatonin kills or inhibits the proliferation of different cancer cell types, and this is associated with an increase or a decrease in reactive oxygen species, respectively. Intracellular oxidants originate mainly from oxidative metabolism, and cancer cells frequently show alterations in this metabolic pathway, such as the Warburg effect (aerobic glycolysis. Thus, we hypothesized that melatonin could also regulate differentially oxidative metabolism in cells where it is cytotoxic (Ewing sarcoma cells and in cells where it inhibits proliferation (chondrosarcoma cells. Ewing sarcoma cells but not chondrosarcoma cells showed a metabolic profile consistent with aerobic glycolysis, i.e. increased glucose uptake, LDH activity, lactate production and HIF-1α activation. Melatonin reversed Ewing sarcoma metabolic profile and this effect was associated with its cytotoxicity. The differential regulation of metabolism by melatonin could explain why the hormone is harmless for a wide spectrum of normal and only a few tumoral cells, while it kills specific tumor cell types.

  1. Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract

    Science.gov (United States)

    Namvar, Farideh; Rahman, Heshu Sulaiman; Mohamad, Rosfarizan; Baharara, Javad; Mahdavi, Mahnaz; Amini, Elaheh; Chartrand, Max Stanley; Yeap, Swee Keong

    2014-01-01

    Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 μg/mL (HepG2), 18.75±2.1 μg/mL (MCF-7), 12.5±1.7 μg/mL (HeLa), and 6.4±2.3 μg/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer. PMID

  2. Tomato ( Lycopersicon esculentum ) seeds: new flavonols and cytotoxic effect.

    Science.gov (United States)

    Ferreres, Federico; Taveira, Marcos; Pereira, David M; Valentão, Patrícia; Andrade, Paula B

    2010-03-10

    In this study, seeds of Lycopersicon esculentum Mill. were analyzed by HPLC/UV-PAD/MS(n)-ESI. Fourteen flavonoids were identified, including quercetin, kaempferol, and isorhamnetin derivatives, with 13 of them being reported for the first time in tomato seeds. The major identified compounds were quercetin-3-O-sophoroside, kaempferol-3-O-sophoroside, and isorhamnetin-3-O-sophoroside. A significant cell proliferation inhibition (>80%), against rat basophile leukemia (RBL-2H3) cell line, was observed with this extract (IC(50) = 5980 microg/mL). For acetylcholinesterase inhibitory activity, a concentration-dependent effect was verified (IC(20) = 2400 microg/mL). The same behavior was noted regarding antioxidant capacity, evaluated against DPPH (IC(10) = 284 microg/mL), nitric oxide (IC(25) = 396 microg/L), and superoxide radicals (IC(25) = 3 microg/mL).

  3. Cytotoxic and Antitumor Effects of Curzerene from Curcuma longa.

    Science.gov (United States)

    Wang, Youdi; Li, Jiahong; Guo, Jiquan; Wang, Qiyou; Zhu, Shuguang; Gao, Siyuan; Yang, Chen; Wei, Min; Pan, Xuediao; Zhu, Wei; Ding, Dongmei; Gao, Ruiping; Zhang, Wei; Wang, Junye; Zang, Linquan

    2017-01-01

    Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine Curcuma rhizomes. In this study, anticancer activity of curzerene was examined in both in vitro and in vivo models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC50s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects in vivo. In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both in vitro and in vivo models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development. Georg Thieme Verlag KG Stuttgart · New York.

  4. In Vitro Cytotoxic Effect of Brazilian Green Propolis on Human Laryngeal Epidermoid Carcinoma (HEp-2 Cells

    Directory of Open Access Journals (Sweden)

    Michelle C. Búfalo

    2009-01-01

    Full Text Available Propolis is a sticky dark-colored material showing a very complex chemical composition that honeybees collect from plants. It has been used in folk medicine since ancient times, due to several biological properties, such as antimicrobial, anti-inflammatory, antioxidant and immunomodulatory activities, among others. Its antitumor action in vivo and in vitro has also been reported, using propolis extracts or its isolated compounds. The goal of this work was to evaluate propolis's cytotoxic action in vitro on human laryngeal epidermoid carcinoma (Hep-2 cells. These cells were incubated with different concentrations of this bee product for different time periods, and morphology and the number of viable HEp-2 cells analyzed. Data showed that propolis exhibited a cytotoxic effect in vitro against HEp-2 cells, in a dose- and time-dependent way. Propolis solvent had no effects on morphology and number of viable cells, proving that the cytotoxic effects were exclusively due to propolis components. Since humans have been using propolis for a long time, further assays will provide a better comprehension of propolis's antitumor action.

  5. Cytotoxic effects induced by patulin, sterigmatocystin and beauvericin on CHO-K1 cells.

    Science.gov (United States)

    Zouaoui, Nidhal; Mallebrera, Beatriz; Berrada, Houda; Abid-Essefi, Salwa; Bacha, Hassen; Ruiz, Maria-Jose

    2016-03-01

    Mycotoxins are produced by different genera of fungi; mainly Aspergillus, Penicillium and Fusarium. The natural co-occurrence of beauvericin (BEA), patulin (PAT) and sterigmatocystin (STE) has been proved in feed and food commodities. This study investigates the cytotoxicity of individual and combined mycotoxins BEA, PAT and STE. The cytotoxicity on immortalized ovarian cells (CHO-K1) was evaluated using the MTT assay. After 24, 48 and 72 h, the IC50 values were 2.9 μM for PAT and ranged from 10.7 to 2.2 μM and from 25.0 to 12.5 μM for BEA and STE, respectively. Cytotoxic interactions were assayed by the isobologram method, which provides a combination index (CI) value as a quantitative measure of the three mycotoxin interaction's degree. Binary and tertiary combinations showed a dose dependent effect. At low fraction affected, mycotoxin combinations were synergetic; whereas, at higher fraction affected, the combinations showed additive effect. Our results indicate that the co-occurrence of low concentrations of mycotoxin in food may increase their toxic effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Chromographic Analysis and Cytotoxic Effects of Chlorhexidine and Sodium Hypochlorite Reaction Mixtures.

    Science.gov (United States)

    Nocca, Giuseppina; Ahmed, Hany Mohamed Aly; Martorana, Giuseppe Ettore; Callà, Cinzia; Gambarini, Gianluca; Rengo, Sandro; Spagnuolo, Gianrico

    2017-09-01

    The literature reveals controversies regarding the formation of para-chloroaniline (PCA) when chlorhexidine (CHX) is mixed with sodium hypochlorite (NaOCl). This study aimed to investigate the stability of PCA in the presence of NaOCl and to examine the in vitro cytotoxic effects of CHX/NaOCl reaction mixtures. Different volumes of NaOCl were added to CHX (mix 1) or PCA (mix 2). Upon centrifugation, the supernatant and precipitate fractions collected from samples were analyzed using high-performance liquid chromatography. The cytotoxic effects of both fractions were examined on human periodontal ligament and 3T3 fibroblast cell lines. High-performance liquid chromatographic analysis showed no PCA signal when NaOCl was mixed with CHX (mix 1). In mix 2, the intensity of PCA was decreased when NaOCl was added to PCA, and chromatographic signals, similar to that of CHX/NaOCl, were also observed. The mortality of precipitates exerted on both cell lines was lower compared with that of supernatants. The discrepancy in the data from the literature could be caused by the instability of the PCA in the presence of NaOCl. The CHX/NaOCl reaction mixture exhibits a wide range of cytotoxic effects. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells

    Directory of Open Access Journals (Sweden)

    PAULO MICHEL PINHEIRO FERREIRA

    2015-03-01

    Full Text Available Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells and peripheral blood mononuclear cells (PBMC using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM. Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.

  8. Cytotoxic Effect of Thiabendazole on Hn5 Head and Neck Squamous Cell Carcinoma Cell Line.

    Science.gov (United States)

    Abassi, Amir Jalal; Mohamadnia, Abdolreza; Parhiz, Seyed Alireza; Azizi Moghadam, Nahid; Bahrami, Naghmeh

    2017-09-01

    Evidence shows thiabendazole has the potential to inhibit angiogenesis in melanoma and fibrosarcoma; however, its effect on oral squamous cell carcinoma has not been previously studied. This study sought to assess the cytotoxic effects of thiabendazole on HN5 head and neck squamous carcinoma cell line. HN5 cell lines were exposed to different concentrations of thiabendazole (prepared from 99% pure powder) for 24, 48 and 72 hours. Cell viability was assessed by the methyl thiazol tetrazolium assay, and IC50 of thiabendazole was calculated. Cells were also exposed to different concentrations of thiabendazole for 48 hours to determine its effect on expression and transcription of vascular endothelial growth factor gene. Expression of vascular endothelial growth factor mRNA was assessed by real-time polymerase chain reaction. The vascular endothelial growth factor release was assessed by the enzyme-linked immunosorbent assay test. In all concentrations of thiabendazole except for 200 and 550μM, cell viability was significantly different at different time points (p< 0.05). At 48 and 72 hours, cell viability at all concentrations of thiabendazole (100-650μM) significantly decreased compared to the control group (zero concentration). In addition, cell viability significantly decreased with an increase in thiabendazole concentration. At 48 hours, expression of vascular endothelial growth factor mRNA was significantly lower in presence of 500μM thiabendazole compared to the control group (p< 0.001) and release of vascular endothelial growth factor was inhibited in a dose-dependent manner. Thiabendazole inhibited the proliferation of HN5 cells in a dose-dependent and time-dependent manner. It also inhibited the expression of vascular endothelial growth factor gene.

  9. Fullerene C60 Penetration into Leukemic Cells and Its Photoinduced Cytotoxic Effects

    Science.gov (United States)

    Franskevych, D.; Palyvoda, K.; Petukhov, D.; Prylutska, S.; Grynyuk, I.; Schuetze, C.; Drobot, L.; Matyshevska, O.; Ritter, U.

    2017-01-01

    Fullerene C60 as a representative of carbon nanocompounds is suggested to be promising agent for application in photodynamic therapy due to its unique physicochemical properties. The goal of this study was to estimate the accumulation of fullerene C60 in leukemic cells and to investigate its phototoxic effect on parental and resistant to cisplatin leukemic cells. Stable homogeneous water colloid solution of pristine C60 with average 50-nm diameter of nanoparticles was used in experiments. Fluorescent labeled C60 was synthesized by covalent conjugation of C60 with rhodamine B isothiocyanate. The results of confocal microscopy showed that leukemic Jurkat cells could effectively uptake fullerene C60 from the medium. Light-emitting diode lamp (100 mW cm-2, λ = 420-700 nm) was used for excitation of accumulated C60. A time-dependent decrease of viability was detected when leukemic Jurkat cells were exposed to combined treatment with C60 and visible light. The cytotoxic effect of photoexcited C60 was comparable with that induced by H2O2, as both agents caused 50% decrease of cell viability at 24 h at concentrations about 50 μM. Using immunoblot analysis, protein phosphotyrosine levels in cells were estimated. Combined action of C60 and visible light was followed by decrease of cellular proteins phosphorylation on tyrosine residues though less intensive as compared with that induced by H2O2 or protein tyrosine kinase inhibitor staurosporine. All tested agents reduced phosphorylation of 55, 70, and 90 kDa proteins while total suppression of 26 kDa protein phosphorylation was specific only for photoexcited C60.

  10. Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations.

    Science.gov (United States)

    Lu, Biao; Vayssade, Muriel; Miao, Yong; Chagnault, Vincent; Grand, Eric; Wadouachi, Anne; Postel, Denis; Drelich, Audrey; Egles, Christophe; Pezron, Isabelle

    2016-09-01

    Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Effect of heat on the cytotoxicity and interaction with DNA of a series of platinum complexes.

    Science.gov (United States)

    Herman, T S; Teicher, B A; Chan, V; Collins, L S; Abrams, M J

    1989-02-01

    The effect of elevated temperature on the cytotoxicity and interaction with DNA of a series of platinum(II) complexes was examined. CDDP showed greater enhancement in cell killing with heat than the other platinum(II) complexes. There were approximately 2 decades enhancement in cell killing by 10 microM CDDP at 42 degrees C compared to 37 degrees C. The other potential cross-linking agents also showed increasing cytotoxicity with increasing temperature. K2PtCl4 (500 microM) killed about 15 times more cells at 43 degrees C than at 37 degrees C and KPt(NH3)Cl3 (500 microM) killed about 18 times more cells at 43 degrees C than at 37 degrees C. The cytotoxicity of the triammine and tetraammine complexes was less influenced by temperature. There was no significant difference in the cytotoxicity of [Pt(NH3)3Cl]Cl at any of the temperatures examined. The cytotoxicity of [Pt(NH3)4]Cl2 (500 microM) was increased about 7-fold at 43 degrees C compared to 37 degrees C, but the total cell killing by this complex at 43 degrees C was less than 1 log. Carboplatin (250 microM) was about 5 times more toxic at 42 degrees C and killed about 2.5 decades more cells at 43 degrees C than at 37 degrees C. Although there was little enhancement in the cytotoxicity of trans-Pt(NH3)2Cl2 at 42 degrees C compared to 37 degrees C trans-Pt(NH3)2Cl2 (500 microM) was about 7 times more cytotoxic than at 37 degrees C. The interaction of the various drug/temperature treatments with supercoiled pBR322 plasmid DNA was examined to assess the effect of heat on the reaction of these agents with DNA. At 42 degrees C, CDDP was able to gradually alter the gel electrophoretic mobility of the plasmid DNA to near that of the linear form. This change also occurred at 37 degrees C but at a much slower rate. Carboplatin effected similar changes in the superhelical pBR322 DNA, and the effect of temperature appeared to increase the rate of the reaction. Trans-Pt(NH3)2Cl2 also interacted with the supercoiled DNA, but

  12. Conventional and whitening toothpastes: cytotoxicity, genotoxicity and effect on the enamel surface.

    Science.gov (United States)

    Camargo, Samira Esteves Afonso; Jóias, Renata Pilli; Santana-Melo, Gabriela Fátima; Ferreira, Lara Tolentino; El Achkar, Vivian Narana Ribeiro; Rode, Sigmar de Mello

    2014-12-01

    To evaluate the cytotoxicity and genotoxicity of whitening and common toothpastes, and the surface roughness of tooth enamel submitted to brushing with both toothpastes. Samples of whitening toothpastes [Colgate Whitening (CW) and Oral-B Whitening (OBW)] and regular (non-whitening) toothpastes (Colgate and Oral-B) were extracted in culture medium. Gingival human fibroblasts (FMM-1) were placed in contact with different dilutions of culture media that had been previously exposed to such materials, and the cytotoxicity was evaluated using the MTT assay. The genotoxicity was assessed by the micronucleus formation assay in Chinese hamster fibroblasts (V79). The cell survival rate and micronuclei number were assessed before and after exposure to the toothpaste extracts. For the surface roughness evaluation, 20 bovine tooth specimens, divided into four groups according to toothpastes, were submitted to 10,000 brushing cycles. The results were analyzed using the Mann-Whitney U and two-way ANOVA tests (P toothpaste (P whitening toothpastes showed the highest numbers of micronuclei compared to the untreated control (UC) (P toothpastes were not genotoxic compared to UC (P = 0.326). The OBW toothpaste was statistically significantly abrasive to the enamel surface (P whitening toothpastes and Oral-B were cytotoxic to the cells. The whitening toothpastes were more genotoxic to cells in vitro than the common toothpastes, and genotoxicity was more pronounced in the OBW toothpaste.

  13. In vitro cytotoxic, genotoxic and antioxidant/oxidant effects of guaiazulene on human lymphocytes

    Directory of Open Access Journals (Sweden)

    Başak Toğar

    2015-02-01

    Full Text Available The aim of this study was to evaluate for the cytotoxicity, genotoxicity and antioxidant/oxidant activity of GYZ on human peripheral blood lymphocytes (PBLs. Guaiazulene (GYZ was added into culture tubes at various concentrations (0-400 µg/mL-1. Cytotoxicity against the human lymphocytes cultures was examined by lactate dehydrogenase (LDH release assay. The proliferative response was estimated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay. Antioxidant/oxidant activity was evaluated by measuring the total oxidant status (TOS and total antioxidant capacity (TAC levels. Micronucleus (MN and chromosomal aberration (CA tests were used in genotoxicity studies. The results showed that GYZ caused cytotoxicity in the PBLs at high concentrations, but TOS level were not affected, while the level of TAC was significantly increased. GYZ also did not induce chromosomal aberrations when compared to that of the control group. Results this study clearly revealed that GYZ was not genotoxic and also increased the capacity of the antioxidant in the culture of human PBL cells. This report is first report on the impact of GYZ on human PBL cells.

  14. Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in human urothelial carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kuo-How Huang

    Full Text Available Celecoxib, a cyclooxygenase-2 (COX-2 inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA, bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC.

  15. Synthesis of silver nanoparticles using flavonoids: hesperidin, naringin and diosmin, and their antibacterial effects and cytotoxicity

    Science.gov (United States)

    Sahu, Nidhi; Soni, Deepika; Chandrashekhar, B.; Satpute, D. B.; Saravanadevi, Sivanesan; Sarangi, B. K.; Pandey, R. A.

    2016-07-01

    Three different flavonoids -hesperidin, naringin and diosmin (constituents of citrus plants) were used for the synthesis of silver nanoparticles (AgNPs). Aqueous solutions of pure flavonoids (0.2 mg mL-1) mixed with 1 mM AgNO3 solution were exposed to bright sunlight to prepare the nanoparticles. Characterization of the synthesized nanoparticles by UV-Visible spectrophotometer, X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy revealed that the synthesized silver nanoparticles were 10-80 nm in size and polydispersed in nature. Bactericidal effect against common pathogens and cytotoxicity of the synthesized silver nanoparticles was investigated on human promyelocytic leukemic (HL-60) cells. It is concluded that AgNPs synthesized using Naringin as reducing agent showed higher stability and better antibacterial and cytotoxic activities.

  16. Exposure of the murine RAW 264.7 macrophage cell line to dicalcium silicate coating: assessment of cytotoxicity and pro-inflammatory effects.

    Science.gov (United States)

    Chen, Liangjiao; Zhang, Yanli; Liu, Jia; Wei, Limin; Song, Bin; Shao, Longquan

    2016-03-01

    Inflammatory effects are significant elements of the immune response to biomaterials. Previously, we reported inflammatory effects in response to dicalcium silicate (Ca2SiO4, C2S) particles. However, the immunological effects of C2S coatings have not been studied. C2S often used as coatings materials in orthopedic and dentistry applications. It may have different effect from C2S particles. Further, it remains unclear whether C2S coating is equally biocompatible as 45S5 coating. The aim of this study was to test the cytotoxicity and pro-inflammatory effects of C2S coating on RAW 264.7 macrophages. C2S and 45S5 coatings were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive analysis (EDS) and X-ray diffraction (XRD). inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to detect ionic concentrations after soaking coated discs in medium. The cytotoxicity of C2S and 45S5 coatings against RAW 264.7 macrophages was measured using the LDH Cytotoxicity Assay Kit, Cell Counting Kit-8 (CCK-8) assays and flow cytometry for apoptosis assays. The gene and protein expression of TNF-α, IL-6 and IL-1β were detected using RT-q PCR and ELISA, respectively. The tested coating materials are not cytotoxic to macrophages. The C2S-coated surface stimulated macrophages to express pro-inflammatory mediators, such as TNF-α, IL-6 and IL-1β, and C2S coating caused less IL-6 but greater IL-1β production than the 45S5 coating. C2S coating have no cytotoxicity when directly cultured with macrophages. C2S and 45S5 coatings both have the potential to induce pro-inflammatory effects, and the biocompatibility of C2S is similar to that of 45S5.

  17. Cytotoxicity induced by ochratoxin A, zearalenone, and α-zearalenol: effects of individual and combined treatment.

    Science.gov (United States)

    Wang, H W; Wang, J Q; Zheng, B Q; Li, S L; Zhang, Y D; Li, F D; Zheng, N

    2014-09-01

    This study investigated the cytotoxicity of combined mycotoxins of ochratoxin A (OTA), zearalenone (ZEA), and/or α-zearalenol (α-ZOL). The cytotoxicity of two mycotoxin combinations (two two-toxin combinations and one three-toxin combination) on human Hep G2 cells was evaluated using a tetrazolium salt (MTT) assay and isobologram analysis. Our results demonstrated significant cytotoxic effects of the two-toxin combination and the three-toxin combination on Hep G2 cells in a time- and concentration-dependent manner. The combination indexes (CI) were 2.73-7.67 for the OTA+ZEA combination and 1.23-17.82 for the OTA+α-ZOL combination after 24 h, 48 h, and 72 h of exposure at all inhibit concentration (IC) levels (IC10-IC90), indicating an antagonism. The CIs of the ZEA+α-ZOL combination were 1.29-2.55 after 24 h and 72 h of exposure (IC10-IC90), indicating an antagonism. The CIs of the ZEA+α-ZOL combination were 0.74-1.68 after 48 h of exposure, indicating synergism (IC80-IC90), additive effects (IC50-IC70), or antagonism (IC10-IC40). For the OTA+ZEA+α-ZOL combination, the CIs were 1.41-14.65 after 24 h, 48 h, and 72 h of exposure (IC10-IC90), indicating an antagonism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Improved cytotoxic effects of Salmonella-producing cytosine deaminase in tumour cells.

    Science.gov (United States)

    Mesa-Pereira, Beatriz; Medina, Carlos; Camacho, Eva María; Flores, Amando; Santero, Eduardo

    2015-01-01

    In order to increase the cytotoxic activity of a Salmonella strain carrying a salicylate-inducible expression system that controls cytosine deaminase production, we have modified both, the vector and the producer bacterium. First, the translation rates of the expression module containing the Escherichia coli codA gene cloned under the control of the Pm promoter have been improved by using the T7 phage gene 10 ribosome binding site sequence and replacing the original GUG start codon by AUG. Second, to increase the time span in which cytosine deaminase may be produced by the bacteria in the presence of 5-fluorocytosine, a 5-fluorouracyl resistant Salmonella strain has been constructed by deleting its upp gene sequence. This new Salmonella strain shows increased cytosine deaminase activity and, after infecting tumour cell cultures, increased cytotoxic and bystander effects under standard induction conditions. In addition, we have generated a purD mutation in the producer strain to control its intracellular proliferation by the presence of adenine and avoid the intrinsic Salmonella cell death induction. This strategy allows the analysis and comparison of the cytotoxic effects of cytosine deaminase produced by different Salmonella strains in tumour cell cultures. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  19. Microbial-assisted synthesis and evaluation the cytotoxic effect of tellurium nanorods

    Energy Technology Data Exchange (ETDEWEB)

    Forootanfar, Hamid [Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Amirpour-Rostami, Sahar; Jafari, Mandana [Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Forootanfar, Amir [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Yousefizadeh, Zahra [The Student Research Committee, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Shakibaie, Mojtaba, E-mail: shakiba@kmu.ac.ir [Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of)

    2015-04-01

    The present study was designed to isolate bacterial strain capable of tellurium nanorods' (Te NRs) production followed by purification and evaluation of the cytotoxic effect of Te NRs. Among 25 environmental samples collected for screening of Te NR-producer bacterial strains one bacterial colony (isolated from hot spring and identified as Pseudomonas pseudoalcaligenes strain Te) was selected and applied for biosynthesis of Te NRs. Thereafter, an organic–aqueous partitioning system was applied for the purification of the biogenic Te NRs and the purified Te NRs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV–visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. The cytotoxic effect of biologically synthesized Te NRs and potassium tellurite on four cell lines of MCF-7, HT1080, HepG2 and A549 was then determined using the MTT assay method. The obtained results revealed lower toxicity for the rod-shaped biogenic tellurium nanostructures (~ 22 nm diameter by 185 nm length) compared to K{sub 2}TeO{sub 3}. - Highlights: • Te NR producing bacterial strain were isolated from hot springs. • Organic–aqueous partitioning system was applied for purification of Te nanorods. • The rod-shaped biogenic Te NPs showed lower cytotoxicity compared to K{sub 2}TeO{sub 3}.

  20. δ-Aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    del Batlle Alcira M

    2002-03-01

    Full Text Available Abstract Background Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, δ-aminolevulinic acid (ALA and porphobilinogen (PBG. ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. Results We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations.

  1. Cytotoxicity and apoptotic effects of nickel oxide nanoparticles in cultured HeLa cells

    Directory of Open Access Journals (Sweden)

    Kezban Ada

    2010-04-01

    Full Text Available The aim of this study was to observe the cytotoxicity and apoptotic effects of nickel oxide nanoparticles on humancervix epithelioid carcinoma cell line (HeLa. Nickel oxide precursors were synthesized by an nickel sulphate-excess ureareaction in boiling aqueous solution. The synthesized NiO nanoparticles (<200 nm were investigated by X-ray diffractionanalysis and transmission electron microscopy techniques. For cytotoxicity experiments, HeLa cells were incubated in50-500 μg/mL NiO for 2, 6, 12 and 16 hours. The viable cells were counted with a haemacytometer using light microscopy.The cytotoxicity was observed low in 50-200 μg/mL concentration for 16 h, but high in 400-500 μg/mL concentration for2-6 h. HeLa cells' cytoplasm membrane was lysed and detached from the well surface in 400 μg/mL concentration NiOnanoparticles. Double staining and M30 immunostaining were performed to quantify the number of apoptotic cells in cultureon the basis of apoptotic cell nuclei scores. The apoptotic effect was observed 20% for 16 h incubation.

  2. Cytotoxic Effects of Re-Activated Lunar Dust Stimulant on Human Lung Cells

    Science.gov (United States)

    Upadhyaya, Krishna

    2009-01-01

    Lunar dust has been of significant concern due to various problems observed on the Apollo missions. Reports from astronauts have shown that the dust may have caused eye and nasal irritation as well as possible hay fever like symptoms. As NASA hopes to go to the Moon within the next few years, we hope to understand the possible toxic effects the dust might have. In these studies, we are looking at the effect of "re-activated" lunar dust stimulant on human bronchial cells. A simple grinding analog as a method of simulating micrometeorite crushing on the moon is used to "activate" the dust stimulant, i.e. capable of producing hydroxyl radicals. These radicals could then interact with human cells and may lead to a loss in membrane integrity and cell death. (Castranova, 1994) Cells are exposed to the dust for 6 and 24 hour intervals to assess cytotoxicity. Cytotoxicity is measured by looking at the production of inflammatory cytokines. Cells are exposed to ground and unground stimulant and compared to cytokine production from cells exposed to quartz which have a known toxicity. Here we look at the cytotoxicity of the lunar dust stimulant relative to quartz by measuring the production of inflammatory cytokines.

  3. Cytotoxic effects of mistletoe (Viscum album L.) in head and neck squamous cell carcinoma cell lines.

    Science.gov (United States)

    Klingbeil, Ma Fátima G; Xavier, Flávia C A; Sardinha, Luiz R; Severino, Patricia; Mathor, Monica B; Rodrigues, Rodrigo V; Pinto, Décio S

    2013-11-01

    Head and neck squamous cell carcinoma is a complex disease with several etiologic factors and different molecular changes that may trigger certain events; it is also globally one of the most common malignancies in this topography. Extracts from Viscum album L. (VA) (mistletoe) have been used as adjuvant therapies with promising results in several types of cancer, mainly in European countries. In vitro studies have demonstrated that various types of VA may have cytotoxicity in carcinoma cells, activating the apoptotic cascade or leading cells to necrosis. This study aimed to verify the effects of three types of VA extracts (Iscador Qu Spezial, Iscador P and Iscador M) in squamous cell carcinoma of the tongue cell lines SCC9 and SCC25, not previously studied. A concentration of 0.3 mg/ml (IC50) of the drugs induced apoptosis, affecting gene expression and protein levels of AKT, PTEN and CYCLIN D1. It was concluded that VA extracts have a cytotoxic effect on SCC9 and SCC25 cell lines, but while SCC9 cell line was more resistant to the action of the drugs, Iscador Qu Spezial and Iscador M have higher cytotoxic potential in both cell lines compared to Iscador P.

  4. The cytotoxic and growth inhibitory effects of palladium(II complexes on MDA-MB-435 cells

    Directory of Open Access Journals (Sweden)

    Nathália Cristina Campanella

    2012-01-01

    Full Text Available The antitumorigenic potential of two palladium(II complexes, [Pd(ca2-o-phenCl2 ] - C1 and [Pd(dmba(dpppCl] - C2, was evaluated, using MDA-MB-435 cells, a human breast adenocarcinoma cell-line that does not express the estrogen receptor α (ER-. Growth inhibition and induced alterations in cell-morphology were analyzed. The sulforhodamine B test showed that, compared to control cells, both C1 and C2 significantly inhibited (p < 0.5 cell growth. The maximum effect with both was achieved with 1 µM complexes, after 24 h of treatment. No further cell-growth inhibition was achieved by increasing concentration or incubation time. Cell morphology was analyzed after staining with hematoxylin-eosin (HE. The morphological changes noted in the treated cells were cell rounding-up, shrinkage, nuclear condensation and reduction of cell length (p < 0.05, thereby indicating that both C1 and C2 are cytotoxic to breast adenocarcinoma cells. All together, there was every indication that, by decreasing cell growth and inducing morphological changes, the tested complexes are cytotoxic, hence their potentiality as promising candidates for antineoplastic drug development.

  5. The potential of synthetic thiourea compound to reduce the cytotoxic and genotoxic effects of paraquat in Hordeum vulgare and cultured human lymphocytes.

    Science.gov (United States)

    Gateva, Svetla; Jovtchev, Gabriele; Stergios, Mila; Yonova, Petranka

    2012-03-01

    This work evaluated the ability of one synthetic compound 1-(4-fluorophenylthiocarbamoyl)-4-methyl-piperazine (FTMP), thiourea derivative to reduce cytotoxic and genotoxic effects of free radical inducer paraquat (PQ) in two different test systems Hordeum vulgare and human lymphocytes in vitro. The mitotic index was used as a marker for cytotoxicity. To indicate genotoxicity, chromosome aberrations test and micronucleus induction test were used. FTMP manifested a weak genotoxic effect in both test systems. Clear evidence was obtained that conditioning treatment with FTMP (10(-6) , 5 × 10(-6) , and 10(-5) mol/l) could decrease chromosome aberrations and micronuclei induced by PQ in both test systems. "Aberration hot spots" in heterochromatin containing segments were reduced. The present data show that the thiourea synthetic compound FTMP provides genome protection against the harmful action of oxidative stress inductor PQ. Human lymphocytes were found to be more sensitive to the cytotoxic and clastogenic effects of FTMP conditioning treatment than Hordeum vulgare. Revealing the protective action of newly synthesized compounds could contribute to the improvement of our present knowledge of the mechanisms of mutagenesis and antimutagenesis. Copyright © 2010 Wiley Periodicals, Inc.

  6. Cytotoxic effect of novel dehydroepiandrosterone derivatives on different cancer cell lines.

    Science.gov (United States)

    Garrido, Mariana; Cabeza, Marisa; Cortés, Francisco; Gutiérrez, José; Bratoeff, Eugene

    2013-10-01

    The aim of this study was to determine the cytotoxic effect of human cancer cells on three series of novel dehydroepiandrosterone derivatives containing triazole or pyrazole rings at C-17 and an ester moiety at C-3 of the androstane skeleton. The panel cancer cells used in this study were the following: PC-3, MCF-7 and SKLU-1. The results from this study indicated that the steroidal derivatives 4a-4e and 4f-4k showed the highest cytotoxic potency. This difference in this activity could be attributed to the ability of the triazole (three nitrogen atoms) to form stronger hydrogen bonds with the active site of the cell as compared to the pyrazole group having two nitrogen atoms. Compounds 4f-4k having an aromatic ester at C-3 showed an enhanced cytotoxic activity as compared to their aliphatic counterparts 4a-4e. Apparently the electronegative phenyl ring increased the polarity of the molecule, thus increasing the dipole-dipole association of the steroidal molecule with the reactive site of the cell. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Effect of biflavones of Ginkgo biloba against UVB-induced cytotoxicity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong-Jin [Chonnam National Univ., Kwangju (Korea, Republic of). Medical School

    2001-04-01

    The effect of Ginkgo biloba extract on Ultraviolet B (UVB) irradiated fibroblasts was examined by using a neutral red dye uptake assay and a lactic dehydrogenase (LDH) release assay. Crude extract along with individual components, including flavone-glycosides and biflavones, were applied to cultured normal human skin fibroblasts for 12 hours, and 0, 20, 40 and 80 mJ/cm{sup 2} of UVB were irradiated. Two synthetic flavonoids, quercetin and rutin, which have polyphenol structures close to the flavonoids in Ginkgo biloba extract, were used to compare any structure-related activity under the same conditions. At the concentrations (from 0.25 to 2 mg/ml) treated with biflavone components (isoginkgetin/ginkgetin, sciadopitysin) and quercetin, high neutral red dye uptake was detected with gradual increases in UVB irradiation. The time-course release of LDH was determined as the cytotoxicity index (%) during 24 hours following a high dose UVB irradiation (200 mJ/cm{sup 2}), and the pattern of this cytotoxicity index was similar to that of the neutral red dye uptake results. Sciadopitysin, isoginkgetin/ginkgetin and quercetin treatments lowered cytotoxicity indices to 50.81, 67.81 and 62.19%, respectively, compared to 95.38% for the untreated control. The antioxidant potential of biflavones of Ginkgo biloba could be explained on the basis of structure-related activity; hydroxy- and methyl-substitutions on the basic structure of these flavonoids played a role, as other reports have suggested. (author)

  8. ROS-mediated cytotoxic effect of copper(II) hydrazone complexes against human glioma cells.

    Science.gov (United States)

    Recio Despaigne, Angel A; Da Silva, Jeferson G; da Costa, Pryscila R; Dos Santos, Raquel G; Beraldo, Heloisa

    2014-10-27

    2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

  9. ROS-Mediated Cytotoxic Effect of Copper(II Hydrazone Complexes against Human Glioma Cells

    Directory of Open Access Journals (Sweden)

    Angel A. Recio Despaigne

    2014-10-01

    Full Text Available 2-Acetylpyridine acetylhydrazone (H2AcMe, 2-benzoylpyridine acetylhydrazone (H2BzMe and complexes [Cu(H2AcMeCl2] (1 and [Cu(H2BzMeCl2] (2 were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

  10. Synergistic cytotoxic effects of arsenite and tetrandrine in human breast cancer cell line MCF-7.

    Science.gov (United States)

    Yao, Mingjiang; Yuan, Bo; Wang, Xiao; Sato, Ai; Sakuma, Kana; Kaneko, Kurumi; Komuro, Hana; Okazaki, Ayane; Hayashi, Hideki; Toyoda, Hiroo; Pei, Xiaohua; Hu, Xiaomei; Hirano, Toshihiko; Takagi, Norio

    2017-08-01

    To provide novel insight into the development of new therapeutic strategies to combat breast cancer using trivalent arsenic (AsIII)-based combination therapy, the cytotoxicity of a combination of AsIII and tetrandrine (Tetra), a Chinese plant-derived alkaloid, was investigated in the human breast cancer cell line MCF-7. Cytotoxicity was evaluated using cell viability, colony formation, wound healing, lactate dehydrogenase leakage and cell cycle assay. Alterations of genes associated with cell proliferation and death were analyzed using real-time PCR and western blotting. Intracellular arsenic accumulation (As[i]) was also determined. Tetra significantly enhanced the cytotoxicity of AsIII in MCF-7 cells in a synergistic manner. The combined treatment upregulated the expression level of FOXO3a, and subsequently resulted in a concomitant increase in the expression levels of p21, p27, and decrease of cycline D1, which occurred in parallel with G0/G1 phase arrest. Autophagy induction was also observed in the combination treatment. Importantly, combining AsIII with Tetra exhibited a synergistic inhibitory effect on the expression level of survivin. Furthermore, enhanced As[i] along with synergistic cytotoxicity was observed in MCF-7 cells treated with AsIII combined with Tetra or Ko134, an inhibitor of breast cancer resistance protein (BCRP), suggesting that Tetra or the BCRP inhibitor probably intervened in the occurrence of resistance to arsenic therapy by enhancing the As[i] via modulation of multidrug efflux transporters. These results may provide a rational molecular basis for the combination regimen of AsIII plus Tetra, facilitating the development of AsIII-based anticancer strategies and combination therapies for patients with solid tumors, especially breast cancer.

  11. Effects of organic extracts of six Bangladeshi plants on in vitro thrombolysis and cytotoxicity

    Directory of Open Access Journals (Sweden)

    Rahman M Atiar

    2013-01-01

    Full Text Available Abstract Background Thrombus formed in blood vessels lead to atherothrombotic diseases such as myocardial or cerebral infarction. Thrombolytic agents are used to dissolve the already formed clots in the blood vessels; however, these drugs sometimes cause serious and fatal consequences. Herbal preparations have been used since ancient times for the treatment of several diseases although they show little toxicity in some cases. Aqueous extracts of herbs used in thrombolysis have been reported before with cytotoxic data, however, the organic extracts of herbs have not been documented. This study aims to investigate whether organic extracts possess thrombolytic properties with minimal or no toxicity. Methods An in vitro thrombolytic model was used to check the clot lysis effect of six Bangladeshi herbal extracts viz., Ageratum conyzoides L., Clausena suffruticosa, Leea indica (Burm.f. Merr., Leucas aspera Willd., Senna sophera L. Roxb., and Solanum torvum Swartz. using streptokinase as a positive control and water as a negative control. Briefly, venous blood drawn from twenty healthy volunteers was allowed to form clots which were weighed and treated with the test plant materials to disrupt the clots. Weight of clot after and before treatment provided a percentage of clot lysis. Cytotoxicity was screened by brine shrimp lethality bioassay using vincristine sulfate as positive control. Results Using an in vitro thrombolytic model, Ageratum conyzoides, Clausena suffruticosa, Leea indica, Leucas aspera, Senna sophera and Solanum torvum showed 18.12 ± 2.34%, 48.9 ± 2.44%, 39.30 ± 0.96%, 37.32 ± 2.00%, 31.61 ± 2.97% and 31.51 ± 0.57% and clot lysis respectively. Among the herbs studied Clausena suffruticosa, Leea indica and Leucas aspera showed very significant (p Ageratum conyzoides, Clausena suffruticosa, Leea indica, Leucas aspera, Senna sophera and Solanum torvum showed LC50 values 508.86 ± 6.62,41.16 ± 1.26, 2.65 ± 0.16, 181.67 ± 1.65, 233

  12. Evaluation of the cytotoxic effect and antibacterial, antifungal, and antiviral activities of Hypericum triquetrifolium Turra essential oils from Tunisia

    Science.gov (United States)

    2013-01-01

    Background A number of bio-active secondary metabolites have been identified and reported for several Hypericum species. Many studies have reported the potential use of the plant extracts against several pathogens. However, Hypericum triquetrifolium is one of the least studied species for its antimicrobial activity. The aim of the present study was to evaluate the cytotoxic effect of the essential oils of Hypericum triquetrifolium as well as their antimicrobial potential against coxsakievirus B3 and a range of bacterial and fungal strains. Methods The essential oils of Hypericum triquetrifolium harvested from five different Tunisian localities (Fondouk DJedid, Bou Arada, Bahra, Fernana and Dhrea Ben Jouder) were evaluated for their antimicrobial activities by micro-broth dilution methods against bacterial and fungal strains. In addition, the cytotoxic effect and the antiviral activity of these oils were carried out using Vero cell lines and coxsakievirus B3. Results The results showed a good antibacterial activities against a wide range of bacterial strains, MIC values ranging between 0.39-12.50 mg/ml and MBC values between 1.56-25.0 mg/ml. In addition, the essential oils showed promising antifungal activity with MIC values ranging between 0.39 μg/mL and 12.50 μg/mL; MFC values ranged between 3.12 μg/mL and 25.00 μg/mL; a significant anticandidal activity was noted (MIC values comprised between 0.39 μg/mL and 12.50 μg/mL). Although their low cytotoxic effect (CC50 ranged between 0.58 mg/mL and 12.00 mg/mL), the essential oils did not show antiviral activity against coxsakievirus B3. Conclusion The essential oils obtained from Hypericum triquetrifolium can be used as antimicrobial agents and could be safe at non cytotoxic doses. As shown for the tested essential oils, comparative analysis need to be undertaken to better characterize also the antimicrobial activities of Hypericum triquetrifolium extracts with different solvents as well as their

  13. Cytotoxic and Genotoxic effects of Orthodontic Adhesives on Human lymphocyte – An In-vitro Study

    OpenAIRE

    S, Ravi M; R, Vijay; N, Suchetha Kumari; Panchasara, Chirag

    2014-01-01

    Aim of this study was to evaluate the in vitro genotoxicity and cytotoxicity of two orthodontic adhesives and to determine the type of cell death they induce on human lymphocytes. The materials tested were 1.Light cure orthodontic adhesive with conventional primer (Transbond XT3M) and 2. Self cure orthodontic adhesive (Unite, 3M). Cured sterile individual masses were immersed in DMEM and left at 370C for 24 h. Then a volume of 200 μL of the extract medium was mixed with human peripheral bloo...

  14. Sesquiterpene lactones from Inula britannica and their cytotoxic and apoptotic effects on human cancer cell lines.

    Science.gov (United States)

    Bai, Naisheng; Lai, Ching-Shu; He, Kan; Zhou, Zhu; Zhang, Li; Quan, Zheng; Zhu, Nanqun; Zheng, Qun Yi; Pan, Min-Hsiung; Ho, Chi-Tang

    2006-04-01

    Three new sesquiterpenes (1-3), together with four known sesquiterpene lactones, were isolated from the flowers of Inula britannica var. chinensis. Structures were established on the basis of high-field 1D and 2D NMR methods supported by HRMS. All sesquiterpene lactones were tested for cytotoxicity as well as apoptotic ratio in human COLO 205, HT 29, HL-60, and AGS cancer cells. Compounds 3 and 4, two alpha-methylene gamma-lactone-bearing sesquiterpenes, were modestly active in these assays.

  15. Cytotoxic Effect of Nano-SiO2 in Human Breast Cancer Cells via Modulation of EGFR Signaling Cascades.

    Science.gov (United States)

    Jeon, Donghwan; Kim, Hyungjoo; Nam, Keesoo; Oh, Sunhwa; Son, Seog-Ho; Shin, Incheol

    2017-11-01

    Silica nanoparticles (nano-SiO2) are widely used in many industrial areas and there is much controversy surrounding cytotoxic effects of such nanoparticles. In order to determine the toxicity and possible molecular mechanisms involved, we conducted several tests with two breast cancer cell lines, MDA-MB-231 and Hs578T. After exposure to nano-SiO2, growth, apoptosis, motility of breast cancer cells were monitored. In addition, modulation of signal transduction induced by nano-SiO2 was detected through western blot analysis. Treatment of nano-SiO2 repressed the growth of breast cancer cell lines. It also increased apoptosis and reduced cell motility. Moreover, exposure to nano-SiO2 significantly disturbed the dimerization of epidermal growth factor receptor (EGFR), followed by down-regulation of its downstream cellular sarcoma kinase (c-SRC) and signal transducer and activator of transcription 3 (STAT3) signaling cascades. Nano-SiO2 has a cytotoxic effect on MDA-MB-231 and Hs578T breast cancer cells via modulation of EGFR signaling cascades. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies.

    Directory of Open Access Journals (Sweden)

    Vitor Sueth-Santiago

    Full Text Available Curcumin (CUR is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC50 10.13 μM on epimastigotes. Demethoxycurcumin (DMC was equipotent to CUR (IC50 11.07 μM, but bisdemethoxycurcumin (BDMC was less active (IC50 45.33 μM and cyclocurcumin (CC was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel`s mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of T. cruzi in a homology model and the results obtained showed that the observed interactions are in accordance with the IC50 values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations.

  17. Giardial Triosephosphate Isomerase as Possible Target of the Cytotoxic Effect of Omeprazole in Giardia lamblia

    Science.gov (United States)

    Reyes-Vivas, Horacio; de la Mora-de la Mora, Ignacio; Castillo-Villanueva, Adriana; Yépez-Mulia, Lilian; Hernández-Alcántara, Gloria; Figueroa-Salazar, Rosalia; García-Torres, Itzhel; Gómez-Manzo, Saúl; Méndez, Sara T.; Vanoye-Carlo, América; Marcial-Quino, Jaime; Torres-Arroyo, Angélica; Oria-Hernández, Jesús; Gutiérrez-Castrellón, Pedro; Enríquez-Flores, Sergio

    2014-01-01

    Giardiasis is highly prevalent in the developing world, and treatment failures with the standard drugs are common. This work deals with the proposal of omeprazole as a novel antigiardial drug, focusing on a giardial glycolytic enzyme used to follow the cytotoxic effect at the molecular level. We used recombinant technology and enzyme inactivation to demonstrate the capacity of omeprazole to inactivate giardial triosephosphate isomerase, with no adverse effects on its human counterpart. To establish the specific target in the enzyme, we used single mutants of every cysteine residue in triosephosphate isomerase. The effect on cellular triosephosphate isomerase was evaluated by following the remnant enzyme activity on trophozoites treated with omeprazole. The interaction of omeprazole with giardial proteins was analyzed by fluorescence spectroscopy. The susceptibility to omeprazole of drug-susceptible and drug-resistant strains of Giardia lamblia was evaluated to demonstrate its potential as a novel antigiardial drug. Our results demonstrate that omeprazole inhibits giardial triosephosphate isomerase in a species-specific manner through interaction with cysteine at position 222. Omeprazole enters the cytoplasmic compartment of the trophozoites and inhibits cellular triosephosphate isomerase activity in a dose-dependent manner. Such inhibition takes place concomitantly with the cytotoxic effect caused by omeprazole on trophozoites. G. lamblia triosephosphate isomerase (GlTIM) is a cytoplasmic protein which can help analyses of how omeprazole works against the proteins of this parasite and in the effort to understand its mechanism of cytotoxicity. Our results demonstrate the mechanism of giardial triosephosphate isomerase inhibition by omeprazole and show that this drug is effective in vitro against drug-resistant and drug-susceptible strains of G. lamblia. PMID:25223993

  18. Giardial triosephosphate isomerase as possible target of the cytotoxic effect of omeprazole in Giardia lamblia.

    Science.gov (United States)

    Reyes-Vivas, Horacio; de la Mora-de la Mora, Ignacio; Castillo-Villanueva, Adriana; Yépez-Mulia, Lilian; Hernández-Alcántara, Gloria; Figueroa-Salazar, Rosalia; García-Torres, Itzhel; Gómez-Manzo, Saúl; Méndez, Sara T; Vanoye-Carlo, América; Marcial-Quino, Jaime; Torres-Arroyo, Angélica; Oria-Hernández, Jesús; Gutiérrez-Castrellón, Pedro; Enríquez-Flores, Sergio; López-Velázquez, Gabriel

    2014-12-01

    Giardiasis is highly prevalent in the developing world, and treatment failures with the standard drugs are common. This work deals with the proposal of omeprazole as a novel antigiardial drug, focusing on a giardial glycolytic enzyme used to follow the cytotoxic effect at the molecular level. We used recombinant technology and enzyme inactivation to demonstrate the capacity of omeprazole to inactivate giardial triosephosphate isomerase, with no adverse effects on its human counterpart. To establish the specific target in the enzyme, we used single mutants of every cysteine residue in triosephosphate isomerase. The effect on cellular triosephosphate isomerase was evaluated by following the remnant enzyme activity on trophozoites treated with omeprazole. The interaction of omeprazole with giardial proteins was analyzed by fluorescence spectroscopy. The susceptibility to omeprazole of drug-susceptible and drug-resistant strains of Giardia lamblia was evaluated to demonstrate its potential as a novel antigiardial drug. Our results demonstrate that omeprazole inhibits giardial triosephosphate isomerase in a species-specific manner through interaction with cysteine at position 222. Omeprazole enters the cytoplasmic compartment of the trophozoites and inhibits cellular triosephosphate isomerase activity in a dose-dependent manner. Such inhibition takes place concomitantly with the cytotoxic effect caused by omeprazole on trophozoites. G. lamblia triosephosphate isomerase (GlTIM) is a cytoplasmic protein which can help analyses of how omeprazole works against the proteins of this parasite and in the effort to understand its mechanism of cytotoxicity. Our results demonstrate the mechanism of giardial triosephosphate isomerase inhibition by omeprazole and show that this drug is effective in vitro against drug-resistant and drug-susceptible strains of G. lamblia. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  19. Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy-1Phenylethanone and its Protective Effect Against DNA Damage.

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    Alex Lucas Hanusch

    Full Text Available Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy-1-phenylethanone (4NF and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities.

  20. Cytotoxicity effects of water dispersible oxidized multiwalled carbon nanotubes on marine alga, Dunaliella tertiolecta

    Energy Technology Data Exchange (ETDEWEB)

    Wei Liping, E-mail: liping.wei@njit.edu [Department of Chemistry and Environmental Science, New Jersey Institute of Technology, 151 Tiernan Hall, Newark, NJ 07102 (United States); Thakkar, Megha; Chen Yuhong; Ntim, Susana Addo; Mitra, Somenath [Department of Chemistry and Environmental Science, New Jersey Institute of Technology, 151 Tiernan Hall, Newark, NJ 07102 (United States); Zhang Xueyan [Otto York Center, New Jersey Institute of Technology, Newark, NJ 07102 (United States)

    2010-10-15

    The multiwalled carbon nanotubes (MWNTs) are novel materials with many potential applications. The ecotoxicity of these materials is not well studied, but it is essential for environmental impact assessments. In this study a commercially available MWNT material was carboxylated by microwave assisted acid oxidation. This functionalized MWNT (f-MWNT) material was examined for toxicity effects using unicellular marine green alga Dunaliella tertiolecta. D. tertiolecta was exposed to f-MWNT which had been pre-equilibrated with culture media for 24 h. Substantial growth lag phase was observed at 5 and 10 mg L{sup -1} f-MWNT, and the resulting 50% effective concentration (EC50) on 96-h growth was 0.82 {+-} 0.08 mg L{sup -1}. During mid-exponential growth phase cytotoxicity was evidenced at 10 mg L{sup -1} f-MWNT in 36% reduction in exponential growth rate, 88 mV more positive glutathione redox potential (indicative of oxidative stress), 5% and 22% reduction in photosystem II (PSII) quantum yield and functional cross section respectively, all relative to the control cultures. However, when the large f-MWNT aggregates in the media with 10 mg L{sup -1} f-MWNT were removed by 0.2 {mu}m filtration, D. tertiolecta did not show significant cytotoxicity effects in any of the above parameters. This suggests that the cytotoxicity effects originated predominately from the large f-MWNT aggregates. Analysis of the f-MWNT aggregation dynamics suggests active interaction between f-MWNT and algal cells or cell metabolites that promoted f-MWNT aggregation formation. The f-MWNT particles were also found absorbed on algal cell surface. The direct contact between f-MWNT and cell surface was likely responsible for reduced PSII functional cross section and oxidative stress during exponential growth.

  1. Cytotoxic effects of hydroxylated fullerenes on isolated rat hepatocytes via mitochondrial dysfunction.

    Science.gov (United States)

    Nakagawa, Yoshio; Suzuki, Toshinari; Ishii, Hidemi; Nakae, Dai; Ogata, Akio

    2011-11-01

    The cytotoxic effects of hydroxylated fullerenes, also termed fullerenols or fullerols [C(60)(OH)( n )], which are known nanomaterials and water-soluble fullerene derivatives, were studied in freshly isolated rat hepatocytes. The exposure of hepatocytes to C(60)(OH)(24) caused not only concentration (0-0.25 mM)- and time (0-3 h)-dependent cell death accompanied by the formation of cell blebs, loss of cellular ATP, reduced glutathione (GSH), and protein thiol levels, but also the accumulation of glutathione disulfide and malondialdehyde, indicating lipid peroxidation. Of the other analogues examined, the cytotoxic effects of C(60)(OH)(12) and fullerene C(60) at a concentration of 0.125 mM were less than those of C(60)(OH)(24). The loss of mitochondrial membrane potential and generation of oxygen radical species in hepatocytes incubated with C(60)(OH)(24) were greater than those with C(60)(OH)(12) and fullerene C(60). In the oxygen consumption of mitochondria isolated from rat liver, the ratios of state-3/state-4 respiration were more markedly decreased by C(60)(OH)(24) and C(60)(OH)(12) compared with C(60). In addition, C(60)(OH)(24) and C(60)(OH)(12) resulted in the induction of the mitochondrial permeability transition (MPT), and the effects of C(60)(OH)(12) were less than those of C(60)(OH)(24). Taken collectively, these results indicate that (a) mitochondria are target organelles for fullerenols, which elicit cytotoxicity through mitochondrial failure related to the induction of the MPT, mitochondrial depolarization, and inhibition of ATP synthesis in the early stage and subsequently oxidation of GSH and protein thiols, and lipid peroxidation through oxidative stress at a later stage; and (b) the toxic effects of fullerenols may depend on the number of hydroxyl groups participating in fullerene in rat hepatocytes.

  2. Cytotoxicity Screening of Plants of Genus Piper in Breast Cancer ...

    African Journals Online (AJOL)

    pellitorine) or other compounds. Commercial piperine and pellitorine, major compound of P. nigrum, were used to test their cytotoxic effects and compared them with those curcumin, the active compound from turmeric, the cytotoxic effects of which on many cancer cells have been reported [7-9]. Our results revealed that both.

  3. Synergic Effect of α-Mangostin on the Cytotoxicity of Cisplatin in a Cervical Cancer Model

    Directory of Open Access Journals (Sweden)

    Jazmin M. Pérez-Rojas

    2016-01-01

    Full Text Available Cervical cancer is the second leading cause of death among Mexican women. The treatment with cis-diamminedichloroplatinum (II (CDDP has some serious side effects. Alpha-mangostin (α-M, has a protective effect against CDDP-induced nephrotoxicity, as well as antioxidant, antitumor, and anti-inflammatory properties. Hence, we explored the in vitro and in vivo effect of α-M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect of α-M and/or CDDP was measured by the 3-(3,5-dimethylthiazol-2-yl2,5-diphenyltetrazolium assay. Meanwhile, apoptosis, reactive oxygen species (ROS production, and the cell cycle were determined with flow cytometry. For α-M+CDDP treatment, both a coincubation and preincubation scheme were employed. In vivo, xenotransplantation was performed in female athymic BALB/c (nu/nu mice, and then tumor volume and body weight were measured weekly, whereas α-M interfered with the antiproliferative activity of CDDP in the coincubation scheme, with preincubation with α-M+CDDP showing significantly greater cytotoxicity than CDDP or α-M alone, significantly inhibiting average tumor volume and preventing nephrotoxicity. This effect was accompanied by increased apoptosis and ROS production by HeLa cervical cancer cells, as well as an arrest in the cell cycle. These results suggest that α-M may be useful as a neoadjuvant agent in cervical cancer therapy.

  4. Ethanolic Extract Cytotoxic Effect of Zingiber Afficinale in Breast Cancer (MCF7 Cell Line

    Directory of Open Access Journals (Sweden)

    J Tavakkol Afshari

    2010-07-01

    Full Text Available Introduction & Objective: Biological activities of Zingiber afficieale plants have been reported as possessing anticancer, antibacterial, anti ulcer, antifungal, and insecticidal properties. However, its antitumor effects haven't been studied in cancer cell lines. The aim of this study was to investigate the antitumor effect of zingiber afficieale on breast cancer cell lines. Materials & Methods: This experimental study was conducted in 2010 at Mashhad University of medical Sciences. Breast cancer cell line (MCF7 and normal connective tissue cell line (L929 were cultured in DMEM medium. Ethanolic extract of Zingiber afficinale was prepared and cell lines were treated with different concentration of extract (5000 to 78 µg. Cell viability was measured by MTT assay after 24, 48, and 72 hours. The collected data were statistically analyzed by SPSS software. Results: The effects of Zingiber afficinale on cell viability were observed after 48 hours on cell lines. Ginger doses in 2500 µg concentration inhibited 50% of cell growth (IC50 in cell lines after 48 hours. Conclusion: Our study revealed that fresh ginger extract has cytotoxic effects on tumor cells, but it doesn’t have any cytotoxic effect on normal cells. It seems that ginger could be considered as a promising chemotherapeutic agent in cancer treatment.

  5. Effects of taxol and ionizing radiation on cytotoxicity and prostaglandin production in KB, RPMI-2650, SW-13 and L929

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Keon Il [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Wonkwang University, Iksan(Korea, Republic of); Yoo, Dong Soo [Dept. of Oral and Maxillofacial Radiology and Dental Research Institute, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1998-02-15

    The author evaluated the effects of taxol, a microtubular inhibitor, as a possible radiation sensitizer and the production of prostaglandins on three human cancer cell lines (KB, RPMI-2650 and SW-13) and one murine cell line (L929). Each cell line was divided into four groups (control, taxol only, radiation only and combination of taxol and radiation). The treatment consisted of a single irradiation of 10 Gy and graded doses (5, 50, 100, 200, 300, 500 nM) of taxol for a 24-h period. The cytotoxicity of taxol alone was measured at 1 day after (1-day group) and 4 days after (4-day group) the treatment. The survival ratio of cell was analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyl tetrazolium bromide) test. Prostaglandins (PGE2 and PGI2) were measured in the culture medium by a radioimmunoassay. The results obtained were as follows: 1. There was a significantly in creased cytotoxicity of KB cells in 4-day group than those in 1-day group. There was a high correlation between doses of taxol and cell viability in both groups (1-day group R=0.82741, 4-day group R=0.84655). 2. There was a significantly increased cytotoxicity of RPMI-2650 cells treated with high concentration of taxol in 4-day group than those in 1-day group. Also there was a high correlation between doses of taxol and cell viability in 4-day group (R=0.93917). 3. There was a significantly increased cytotoxicity of SW-13 cell treated with high concentration of taxol in 4-day group than those in 1-day group. However no high correlation was observed between doses of taxol and cell viability in both groups (1-day group R=0.46362, 4-day group R=0.65425). 4. There was a significantly increased cytotoxicity of L929 cells treated with low concentration of taxol in 4-day group than those in 1-day group. At the same time, there was a low correlation between doses of taxol and cell viability in both groups (1-day group R=0.34237, 4-day group R=0.23381). 5. In 1-day group of L929 cells, higher

  6. [Use of cell culture for the research of cytotoxic and antiviral effects of a natural extract of Amaryllidaceae].

    Science.gov (United States)

    Husson, G P; Vilagines, P; Sarrette, B; Vilagines, R

    1995-01-01

    The use of tissue culture for evaluation of antiviral agents can provide rapid information on the toxicity induced by drugs. Toxicity is assessed through 4 different tests: observation through a light microscope, colorimetric evaluation of living cells stained with MTT (Methyl Thiazol Tetrazolium), colorimetric evaluation of fixed cells stained with crystal violet, inhibition of incorporation of radioactive labelled precursors specific to the synthesis under study. These tests allowing evaluation of effects on cell morphological changes (1), of modifications of mitochondrial and enzymatic activities in the cytoplasm (2), of effects on cell growth (3) and on their major synthesis [ADN, ARN, proteins] (4). This design of experiments has been applied to an hydroalcoolic extract from Haemanthus albiflos (Amaryllidaceae) tested for its antiviral properties towards Poliovirus type 1 propagated on monkey kidney cells line (MA 104). The maximum tolerated dose by the cell and the inhibition of virus replication were determined according to tests 2 and 3. The sensitive step of the virus replication cycle was investigated using test 4. Concentration of 7 microliters/ml plant extract showed: 20% cytotoxicity (MTT test). At 7 microliters/ml plant extract the inhibition of replication virus is 4.5 log units (microplates assay) and inhibition of proteins viral synthesis is 97% compared with the control.

  7. Genotoxic and cytotoxic effects of iron sulfate in cultured human lymphocytes treated in different phases of cell cycle.

    Science.gov (United States)

    Lima, P D L; Vasconcellos, M C; Montenegro, R A; Sombra, C M L; Bahia, M O; Costa-Lotufo, L V; Pessoa, C O; Moraes, M O; Burbano, R R

    2008-04-01

    Iron (Fe) is a common chemical element that is essential for organisms as a co-factor in oxygen transport, but that in high amounts presents a significant risk of neurodegenerative disorders. The objective of this study was to evaluate the mutagenic potential of iron sulfate. The comet assay and chromosome aberration (CA) analysis were applied to determine the DNA-damaging and clastogenic effects of iron sulfate. Human lymphocytes were treated in the quiescent phase for the comet assay and proliferative phase during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle for CA analysis, with 1.25, 2.5 and 5 microg/mL concentrations of FeSO(4).7H2O. All tested concentrations were cytotoxic and reduced significantly the mitotic index (MI) in all phases of the cell cycle. They also induced CA in G1, G1/S and S (pulses of 1 and 6 h) phases. Iron sulfate also induced polyploidy in cells treated during G1. In the comet assay, this metal did not induce significant DNA damage. Our results show that Fe causes alteration and inhibition of DNA synthesis only in proliferative cells, which explain the concomitant occurrence of mutagenicity and cytotoxicity, respectively, in the lymphocytes studied.

  8. Choosing safe dispersing media for C60 fullerenes by using cytotoxicity tests on the bacterium Escherichia coli.

    Science.gov (United States)

    Cook, Sean M; Aker, Winfred G; Rasulev, Bakhtiyor F; Hwang, Huey-Min; Leszczynski, Jerzy; Jenkins, Jessica J; Shockley, Vincent

    2010-04-15

    Assessment of C(60) nanotoxicity requires a variety of strategies for dispersing it into biological systems. Our objective was to determine organic solvent/surfactant combinations suitable for this purpose. We used Escherichia coli (ATCC# 25254) to determine the cytotoxicity of C(60) in solvents at concentrations up to 100 ppm. In this preliminary study we hypothesized that C(60) toxicity is directly correlated with its degree of dispersion in solution and that more solubilizing solvents induce higher toxicity. Test solvent concentration (1%) and Tween 80 (0.04%) were based on E. coli viability assay. Sonication was used to further enhance C(60) dispersal. The end-point response was measured with viability (in terms of LC(50)) and general metabolic activity (in terms of IC(50)) of E. coli cultures after exposure. The ultimate goal was to select safe dispersing media and enrich the database of C(60) nanotoxicity for NanoQuantitative-Structure-Activity-Relationship (NanoQSAR) applications. LC(50) range was 30 ppm to >400 ppm. IC(50) followed the trend. Among the six solvent combinations, DMSO combined with Tween 80 was the optimum combination for defining a dose-response relationship for assessing its toxicity to E. coli. However, N,N-dimethylformamide has the greatest potential to be a safe solvent for C(60) applications based upon its biocompatibility. Solvent solubility alone could not account for the cytotoxicity observed in this study. 2009 Elsevier B.V. All rights reserved.

  9. Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells.

    Science.gov (United States)

    Scott, Katherine A; Dennis, Jayne L; Dalgleish, Angus G; Liu, Wai M

    2015-11-01

    Cannabinoids possess a number of characteristics that make them putative anticancer drugs, and their value as such is currently being explored in a number of clinical studies. To further understand the roles that cannabinoids may have, we performed gene expression profiling in glioma cell lines cultured with cannabidiol (CBD) and/or Δ9-tetrahydrocannabinol (THC), and pursued targets identified by this screening. Results showed that a large number of genes belonging to the heat shock protein (HSP) super-family were up-regulated following treatment, specifically with CBD. Increases were observed both at the gene and protein levels and arose as a consequence of increased generation of ROS by CBD, and correlated with an increase in a number of HSP client proteins. Furthermore, increases impeded the cytotoxic effect of CBD; an effect that was improved by co-culture with pharmacalogical inhibitors of HSPs. Similarly, culturing glioma cells with CBD and HSP inhibitors increased radiosensitivity when compared to CBD-alone. Taken together, these data indicate that the cytotoxic effects of CBD can be diminished by HSPs that indirectly rise as a result of CBD use, and that the inclusion of HSP inhibitors in CBD treatment regimens can enhance the overall effect. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Antifungal effect of Sticophus hermanii and Holothuria atra extract and its cytotoxicity on gingiva-derived mesenchymal stem cell

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    Kristanti Parisihni

    2013-12-01

    Full Text Available Background: Sea cucumber had been acknowledged to have some medical properties Sticophus hermanii and Holothuria atra are species of sea cucumber which has been known to have antifungal properties thus potentially explored as therapeutic agent in oral candidiasis. Purpose: The aim of this study was to examine the antifungal property Sticophus hermanii and Holothuria atra extract against Candida albicans and its cytotoxicity to human gingiva-derived mesenchymal stem cell. Methods: The study was an experimental laboratories research with post test only control group design. Methanolic extract of Sticophus hermanii and Holothuria atra in concentrations of 1%, 0.5%; 0.25%; 0.13%, 0.07%; 0.03%, 0.02% and 0.01%; were tested its cytotoxicity on gingiva-derived mesenchymal stem cell. Cell viability were measured by MTT assay. The antifungal property against Candida albicans was tested by disk diffusion method. Data were analyzed by ANOVA followed by LSD. Results: Extract of Sticophus hermanii showed no cytotoxicity in all concentrations (p>0.05, while Holothuria atra showed toxicity in the concentration of 1% and not cytotoxic in the concentrations below (p<0.05. Both sea cucumber extract could inhibit the growth Candida albicans, in vitro, proved by the clear zone around the disc in all concentrations (p<0.05. Conclusion: Stichopus hermanii and Holothuria atra extract had the antifungal effect against Candida albicans. Sea cucumber extract were not cytotoxic togingiva-derived mesenchymal stem cell in the concentration of Sticophus hermanii ≤ 1% and Holothuria atra ≤ 0.5%.Latar belakang: Teripang telah diketahui mempunyai berbagai khasiat medis. Sticophus hermanii dan Holothuria atra adalah spesies teripang yang telah diketahui mempunyai sifat anti jamur sehingga santat potensial untuk diekplorasi sebagai agen terapeutik pada infeksi di rongga mulut. Tujuan: Tujuan dari penelitian ini adalah untuk meneliti sifat anti jamur ekstrak Sticophus hermanii

  11. Comparative Phytochemical Analysis of Essential Oils from Different Biological Parts of Artemisia herba alba and Their Cytotoxic Effect on Cancer Cells

    Science.gov (United States)

    Tilaoui, Mounir; Ait Mouse, Hassan; Jaafari, Abdeslam; Zyad, Abdelmajid

    2015-01-01

    Purpose Carrying out the chemical composition and antiproliferative effects against cancer cells from different biological parts of Artemisia herba alba. Methods Essential oils were studied by gas chromatography coupled to mass spectrometry (GC–MS) and their antitumoral activity was tested against P815 mastocytoma and BSR kidney carcinoma cell lines; also, in order to evaluate the effect on normal human cells, oils were tested against peripheral blood mononuclear cells PBMCs. Results Essential oils from leaves and aerial parts (mixture of capitulum and leaves) were mainly composed by oxygenated sesquiterpenes 39.89% and 46.15% respectively; capitulum oil contained essentially monoterpenes (22.86%) and monocyclic monoterpenes (21.48%); esters constituted the major fraction (62.8%) of stem oil. Essential oils of different biological parts studied demonstrated a differential antiproliferative activity against P815 and BSR cancer cells; P815 cells are the most sensitive to the cytotoxic effect. Leaves and capitulum essential oils are more active than aerial parts. Interestingly, no cytotoxic effect of these essential oils was observed on peripheral blood mononuclear cells. Conclusion Our results showed that the chemical composition variability of essential oils depends on the nature of botanical parts of Artemisia herba alba. Furthermore, we have demonstrated that the differential cytotoxic effect depends not only on the essential oils concentration, but also on the target cells and the botanical parts of essential oils used. PMID:26196123

  12. Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

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    María Verónica Prego-Faraldo

    2016-05-01

    Full Text Available Okadaic acid (OA and dinophysistoxins (DTXs are the main toxins responsible for diarrhetic shellfish poisoning (DSP intoxications during harmful algal blooms (HABs. Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1 comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates.

  13. Biomonitoring of genotoxic and cytotoxic effects of gingival epithelial cells exposed to digital panoramic radiography

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    Anuradha Pai

    2012-01-01

    Full Text Available Objective: The aim of this study was to evaluate genotoxic and cytotoxic effects of low level ionizing radiation used in digital panoramic radiography on gingival epithelial cells. Materials and Methods: We included 50 healthy individuals advised for digital panoramic radiography for diagnostic purpose were included in this study. Demographic data and personal history of all subjects were recorded in a proforma before the examination. Gingival epithelial cells were obtained by gentle scraping with a modified cytobrush immediately before X-ray exposure and 10 ± 2 days later. Cytological preparations were stained according to the Feulgen/fast green method and analyzed under a light microscope. Micronuclei and degenerative nuclear alterations (pyknosis, karyolysis, karyorrhexis and condensed chromatin were scored. Results: The frequency of formation of micronuclei was not significant with regard to age, gender and after exposure to digital panoramic radiography ( P = 0.276. However this study showed significant increase in the frequencies of nuclear alterations like karyorrhexis, pyknosis, condensed chromatin, karyolysis and indicative of cell death ( P < 0.001. Conclusion: Panoramic radiographic examination does not induce genotoxic effect like micronuclei, but it does induce cytotoxic effects leading to cell death.

  14. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

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    Liz Carmem Silva-Pereira

    2014-09-01

    Full Text Available Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

  15. In vitro antimicrobial and cytotoxic effects of Anacardium occidentale and Mangifera indica in oral care.

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    Anand, Geethashri; Ravinanthan, Manikandan; Basaviah, Ravishankar; Shetty, A Veena

    2015-01-01

    Oral health is an integral and important component of general health. Infectious diseases such as caries, periodontal, and gingivitis indicate the onset of imbalance in homeostasis between oral micro biota and host. The present day medicaments used in oral health care have numerous side effects. The uses of herbal plants as an alternative have gained popularity due to side effects of antibiotics and emergence of multidrug resistant strains. Anacardium occidentale (cashew) and Mangifera indica (mango) have been used as traditional oral health care measures in India since time immemorial. The ethanol extracts of cashew and mango leaves were obtained by maceration method. The antimicrobial activity was evaluated by clear zone produced by these plant extracts against Enterococcus faecalis, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Candida albicans in agar plate method, determination of minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC), and suppression of biofilm. The cytotoxic effects of plants extract was determined by microculture tetrazolium assay on human gingival fibroblast and Chinese hamster lung fibroblast (V79) cell lines. Cashew and mango leaf extract significantly (P extracts significantly (P extracts were less cytotoxic (P extracts are superior to the mouth rinses and have a promising role in future oral health care.

  16. The Key Role of Mitochondrial Apoptotic Pathway in the Cytotoxic Effect of Mushroom Extracts on Cancer Cells.

    Science.gov (United States)

    Han, Mei; Ling, Ming-Tat; Chen, Jiezhong

    2015-01-01

    Mushroom extracts have been extensively studied for their medicinal effects. They can stimulate immune responses and thus have been explored in cancer treatment. Recently, it has also been shown that some mushroom extracts can produce direct cytotoxic effect on cancer cells. In this review, we summarize the cytotoxic effect of mushroom extracts in cancer treatment revealed by both in vitro and in vivo studies. We also summarize the current understanding of the mechanisms associated with such an effect with an emphasis on the mitochondrial apoptotic pathway. The recent finding that mushroom extracts have direct cytotoxic effects supplements their known immune stimulating effects. Thus, novel anticancer agents based on new findings from mushroom extracts may soon be added to the present pool of anticancer drugs. Specifically, we propose that nanodelivery of the bioactive compounds of mushroom extracts to mitochondria will further increase their potential treatment efficacy.

  17. Investigation of acute dermal irritation/corrosion, acute inhalation toxicity and cytotoxicity tests for Nanobiocide®

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    Mansour Hemmati

    2016-07-01

    Full Text Available Objective(s: Nanomaterials, especially silver Nanoparticles (Ag-NPs, are employed in an increasing number of commercial products. This has led to an ever growing exposure of human beings to this substance. The first purpose of the Nano Committee of Food and Drug Administration of The Islamic Republic of Iran (IFDA is developing guidelines to assess and approve commercial nano-health products for their safety of human applications. Nanobiocide® as a commercial product of stable colloid including 2000 ppm Ag-NPs for surface antimicrobial applications was investigated according to IFDA guidelines in the approval process. Methods: The first fabrication and characterization method of the product were determined. The human exposure to Nanobiocide® were studied by cytotoxicity assay, dermal irritation and inhalation toxicity assay based on the standard assay. Results: According to cytotoxicity assay by MTT method the concentration-dependent of cell viability was reduced and Inhibitory concentration-50 was about 1160 ppm. The Draize dermal irritation scoring system (DDIS showed no irritation to the skin of rabbits. No sign of gross toxicity, adverse pharmacological effect, or abnormal behavior based on inhalation toxicity was observed. Conclusions: The consideration of toxicity of Nanobiocide® is one of the major key for medical application. The results obtained revealed that the Nanobiocide® may be safe using in domestic and veterinary applications.

  18. Hemolytic and cytotoxic effects of saponin like compounds isolated from Persian Gulf brittle star (Ophiocoma erinaceus

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    Elaheh Amini

    2014-10-01

    Full Text Available Objective: To isolate and characterize the saponin from Persian Gulf brittle star (Ophiocoma erinaceus and to evaluate its hemolytic and cytotoxic potential. Methods: In an attempt to prepare saponin from brittle star, collected samples were minced and extracted with ethanol, dichloromethane, n-buthanol. Then, concentrated n-butanol extract were loaded on HP-20 resin and washed with dionized water, 80% ethanol and 100% ethanol respectively. Subsequently, detection of saponin was performed by foaming property, fourier transform infrared spectroscopy and hemolytic analysis on thin layer chromatography. The cytotoxic activity on HeLa cells was evaluated through 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazoliumbromide (MTT assay and under invert microscopy. Results: The existence of saponin in Ophiocoma erinaceus were approved by phytochemical method. The presence of C-H bond, C-O-C and OH in fourier transform infrared spectrum of fraction 80% ethanol is characteristic feature in the many of saponin compounds. Hemolytic assay revealed HD 50 value was 500 µg/mL. MTT assay exhibited that saponin extracted in IC50 value of 25 µg/mL inducsd potent cytotoxic activity against HeLa cells in 24 h and 12.5 µg/mL in 48 h, meanwhile in lower concentration did not have considerable effect against HeLa cells. Conclusions: These findings showed that only 80% ethanol fraction Persian Gulf brittle star contained saponin like compounds with hemolytic activity which can be detected simply by phytochemical that can be appreciable for future anticancer research.

  19. Application of Coffee Silverskin in cosmetic formulations: physical/antioxidant stability studies and cytotoxicity effects.

    Science.gov (United States)

    Rodrigues, Francisca; Gaspar, Carlos; Palmeira-de-Oliveira, Ana; Sarmento, Bruno; Helena Amaral, M; P P Oliveira, M Beatriz

    2016-01-01

    Currently, there is an increasing interest of cosmetic industry on natural extracts. The inclusion of antioxidants in topical formulations can contribute to minimize oxidative stress in the skin, which has been associated with aging. Also, questions of sustainability are leading to the study of new cosmetic ingredients obtained from food by-products. Coffee Silverskin (CS) is a food by-product with established antioxidant activity that has not yet been incorporated into a topical formulation. The aim of this study was to evaluate the physical and microbiological stabilities and antioxidant activity of a hand cream formulation containing 2.5% (w/w) of CS extract upon production and after 6 months of shelf-life and in vitro safety/cytotoxicity on skin cell lines after production. The in vitro cytotoxicity was evaluated with MTS and LDH assays, at different concentrations, in HaCaT and HFF-1 cells. Formulations were stored at 25 °C/65% RH and 40 °C/75% RH. Physical, microbiological, and antioxidant stabilities were evaluated by centrifugation, viscosity, total colony count, DPPH and total phenolic content (TPC). The hand cream containing 2.5% (w/w) of CS extract showed stable physical characteristics independently of the storage conditions. The DPPH activity and TPC of the CS formulation were significantly higher compared with those of the base formulation. However, during storage, the antioxidant activity decreases slightly. Microbiological quality was also confirmed. No cytotoxic effects were observed. It is possible to suggest that this formulation is stable under extreme conditions and safe for topical use.

  20. Selective cytotoxic effect of 1-O-undecylglycerol in human melanoma cells

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    Marian Hernández-Colina

    2016-04-01

    Full Text Available Context: 1-O-alkylglycerols are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed antineoplastic activity for this family of compounds, structurally related to alkylphospholipids, but the activity of linear chain synthetic alkylglycerols in cancer cell lines is less documented. Melanoma is a high incidence cancer, highly resistant to potential treatments. Finding new anti-cancer compounds to improve melanoma prognosis is a relevant research issue. Aims: To study the cytotoxic effect of 1-O-undecylglycerol in primary cultured normal fibroblasts and A375 human melanoma cell line. Methods: Cells were treated with different concentrations of 1-O-undecylglycerol and viability assessed by MTT assay. Morphological changes were visualized by DAPI and acridine orange-ethidium bromide staining. Mitochondrial membrane potential was evaluated, and gene expression of P53 and BcL-2 was semi-quantified. Results: 1-O-undecylglycerol decreased viability of A375 cells and exerted very low cytotoxicity on primary cultured normal fibroblasts. Necrosis appeared in A375 cells but not in fibroblasts, and no apoptotic changes were visualized in DAPI staining experiments. After 24 h fibroblasts and melanoma cells developed mitochondrial potential changes similar to valinomycin. The gene expression of P53 and BcL-2 decreased in treated cells. Conclusions: 1-O-undecylglycerol exhibited selective cytotoxic activity in A375 melanoma cells when compared with primary cultured fibroblast. Its toxicity is mediated by necrosis that may be related with mitochondrial events and decrease in P53 and BcL-2 expression. The results suggest that UDG could be a useful strategy to combine with other chemotherapeutic agents in melanoma treatment.

  1. Cytotoxicity effects induced by Zearalenone metabolites, alpha Zearalenol and beta Zearalenol, on cultured Vero cells.

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    Othmen, Zouhour Ouanes-Ben; Golli, Emna El; Abid-Essefi, Salwa; Bacha, Hassen

    2008-10-30

    Zearalenone (Zen) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium. It has been implicated in several mycotoxicosis in farm animals and in humans. The major metabolites of this mycotoxin in various species are alpha and beta Zearalenol. In vivo, Zen is mainly reduced to these alcoholic metabolites which cause reproductive tract disorders and impaired fertility due to their estrogenic activities. In this study, we examined the cytotoxicity of alpha and beta Zearalenol in cultured cells. For this purpose, the MTT assay was carried out and the influence of alpha and beta Zearalenol on protein and DNA syntheses was assessed. To evaluate the cell stress caused by these two metabolites, oxidative stress measured by MDA induction and stress protein induction (Hsp 70, Hsp 27) were tested. Results showed that alpha and beta Zearalenol were metabolites that caused cytotoxicity by inhibiting cell viability, protein and DNA syntheses and inducing oxidative damage and over-expression of stress proteins. However, the Zen metabolites exhibited lower toxicity than Zen, with beta zearalenol being the more active of the two metabolites.

  2. Protective effects of steroidal alkaloids isolated from Solanum paniculatum L. against mitomycin cytotoxic and genotoxic actions

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    PABLINE M. VIEIRA

    2013-06-01

    Full Text Available Solanum paniculatum L. is a plant species widespread throughout tropical America, especially in the Brazilian Cerrado region. It is used in Brazil for culinary purposes and in folk medicine to treat liver and gastric dysfunctions, as well as hangovers. Previous studies with S. paniculatum ethanolic leaf extract or ethanolic fruit extract demonstrated that they have no genotoxic activity neither in mice nor in bacterial strains, although their cytotoxicity and antigenotoxicity were demonstrated in higher doses. In order to assess the possible compounds responsible for the activities observed, we fractionated the ethanolic fruit extract of S. paniculatum, characterized by 1H and 13C NMR spectra, and evaluated two fractions containing steroidal alkaloids against mitomycin C (MMC using the mouse bone marrow micronucleus test. Swiss mice were orally treated with different concentrations (25, 50, or 100 mg.kg−1 of each fraction simultaneously with a single intraperitonial dose of MMC (4 mg.kg−1. Antigenotoxicity was evaluated by using the frequency of micronucleated polychromatic erythrocytes (MNPCE, whereas anticytotoxicity was assessed by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE. Our results demonstrated that steroidal alkaloids isolated from S. paniculatum strongly protected cells against MMC aneugenic and/or clastogenic activities as well as modulated MMC cytotoxic action.

  3. In vitro cytotoxic, antioxidant and antiviral effects of Pterocaulon alopecuroides and Bidens segetum extracts

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    Cristiane Silva Silveira

    Full Text Available Pterocaulon alopecuroides (Lamark De Candolle and Bidens segetum Mart. ex Colla are two species belonging to the Asteraceae family. Extracts from those two species were evaluated to their cytotoxic, antioxidant and antiviral activities. All the extracts assayed have shown a very high cytotoxity against RBL-2H3 cell line. The antioxidant assay pointed out a really high activity of the ethyl acetate extracts for B. segetum and P. alopecuroides. This can be partially explained due to the high content of coumarins, at least for P. alopecuroides. None of the total ethanol extracts from B. segetum showed significant activity against the two strains of Herpes simplex virus (Types 1 and 2 resistant to acyclovir. P. alopecuroides ethanol extract was also inactive against the Herpes simplex virus type 1 resistant to acyclovir. However, this extract presented inhibitory activity against the Herpes simplex virus type 2 resistant to acyclovir. From the ethanol crude extract of P. alopecuroides, it was possible to isolate 7-(2',3'-dihidroxy-3'-methylbutyloxy-6-methoxycoumarin, which was tested in the same conditions, showing a viral inhibitory rate almost twice bigger than the P. alopecuroides sample for HSV-2-ACVr. The coumarin was also active against HSV-1-ACVr. Those results provide further evidence of the importance of Pterocaulon alopecuroides and Bidens segetum as medicinal plants.

  4. Enhanced cytotoxic and genotoxic effects of gadolinium following ELF-EMF irradiation in human lymphocytes.

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    Cho, Seunghyun; Lee, Younghyun; Lee, Sunyeong; Choi, Young Joo; Chung, Hai Won

    2014-10-01

    There are many studies of Gd nephrotoxicity and neurotoxicity, whereas research on cyto- and genotoxicity in normal human lymphocytes is scarce. It is important to investigate the effect of extremely low-frequency electromagnetic fields (ELF-EMF) on Gd toxicity, as patients are co-exposed to Gd and ELF-EMF generated by MRI scanners. We investigated the cytotoxicity and genotoixcity of Gd and the possible enhancing effect of ELF-EMF on Gd toxicity in cultured human lymphocytes by performing a micronuclei (MN) assay, trypan blue dye exclusion, single cell gel electrophoresis, and apoptosis analyses using flow cytometry. Isolated lymphocytes were exposed to 0.2-1.2 mM of Gd only or in combination with a 60-Hz ELF-EMF of 0.8-mT field strength. Exposing human lymphocytes to Gd resulted in a concentration- and time-dependent decrease in cell viability and an increase in MN frequency, single strand DNA breakage, apoptotic cell death, and ROS production. ELF-EMF (0.8 mT) exposure also increased cell death, MN frequency, olive tail moment, and apoptosis induced by Gd treatment alone. These results suggest that Gd induces DNA damage and apoptotic cell death in human lymphocytes and that ELF-EMF enhances the cytotoxicity and genotoxicity of Gd.

  5. Investigation of antioxidative, antityrosinase and cytotoxic effects of extract of irradiated oyster mushroom

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    Nutsuda Banlangsawan

    2016-02-01

    Full Text Available Oyster mushroom (Pleurotus ostreatus Fries. is rich in nutrition and has many medicinal properties such as antioxidant and anticancer activities. It also contains a high amount of ergosterol which can be converted to vitamin D2 when exposing to UV light. Oyster mushroom powder was irradiated with UV-B for 180 min and extracted with 95% ethanol. Mushroom extract was determined for vitamin D2 concentration, total phenolic compound, antioxidative activity, tyrosinase inhibitory property and cytotoxicity effect on human keratinocytes (HaCaT and murine melanoma cells (B16F10 by MTT assay. The results demonstrated that the concentration of vitamin D2 of irradiated oyster mushroom extract was 153.96 µg/g, which is 13 times higher than that of non-irradiated mushroom extract. Total phenolic content, antioxidative and tyrosinase inhibitory activities of the two mushroom extracts were not significantly different. Neither oyster mushroom extract had a cytotoxic effect on keratinocytes, but on the other hand both inhibited the growth of murine melanoma cells.

  6. Cytotoxic Effect and TLC Bioautography-Guided Approach to Detect Health Properties of Amazonian Hedyosmum sprucei Essential Oil

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    Alessandra Guerrini

    2016-01-01

    Full Text Available Bioautography has been used as rapid and easy strategy to detect and identify bioactive fractions/molecules in the never before investigated Hedyosmum sprucei Solms (Chloranthaceae essential oil (EO. The antioxidant activity, performed through DPPH bioautographic assay and spectrophotometric evaluations (IC50 = 230 ± 10 µg/mL, seemed to be mainly due to α-cadinol and α-muurolol. (HPTLC bioautography, focused on antimicrobial capacities, pointed out α-cadinol, α-muurolol, τ-muurolol, caryophyllene oxide, and methyleugenol as the most effective compounds against Staphylococcus aureus, considered as testing strain. Moreover, the microdilution method, assessed among a wide panel of microorganisms, revealed Listeria grayi and Staphylococcus aureus as the most sensitive among human tested strains and Clavibacter michiganensis among phytopathogens. GC-MS chemical profile showed that bioactive molecules represented only a small quantity of the whole EO: germacrene D (23.16%, β-caryophyllene (15.53%, δ-cadinene (5.50%, α-copaene (5.08%, and α-phellandrene (3.48% were the main compounds, highlighting an uncommon composition among the genus Hedyosmum. Finally, H. sprucei EO was checked for cytotoxic potential against A549 (lung cancer and MCF-7 (breast cancer cell lines showing promising cytotoxic effects against both cell lines after 48 h (IC50 A549 = 44.05 ± 2.35 µg/mL; IC50 MCF-7 = 32.76 ± 4.92 µg/mL and 72 h (IC50 A549 = 43.55 ± 2.80 µg/mL; IC50 MCF-7 = 33.64 ± 0.43 µg/mL.

  7. Effects of dual antibacterial agents MDPB and nano-silver in primer on microcosm biofilm, cytotoxicity and dentin bond properties

    Science.gov (United States)

    Zhang, Ke; Cheng, Lei; Imazato, Satoshi; Antonucci, Joseph M.; Lin, Nancy J.; Lin-Gibson, Sheng; Bai, Yuxing; Xu, Hockin H. K.

    2013-01-01

    Objectives The objective of this study was to investigate the effects of dentin primer containing dual antibacterial agents, namely, 12-methacryloyloxydodecylpyridinium bromide (MDPB) and nanoparticles of silver (NAg), on dentin bond strength, dental plaque microcosm biofilm response, and fibroblast cytotoxicity for the first time. Methods Scotchbond Multi-Purpose (SBMP) was used as the parent bonding agent. Four primers were tested: SBMP primer control (referred to as “P”), P+5%MDPB, P+0.05%NAg, and P+5%MDPB+0.05%NAg. Dentin shear bond strengths were measured using extracted human teeth. Biofilms from the mixed saliva of 10 donors were cultured to investigate metabolic activity, colony-forming units (CFU), and lactic acid production. Human fibroblast cytotoxicity of the four primers was tested in vitro. Results Incorporating MDPB and NAg into primer did not reduce dentin bond strength compared to control (p>0.1). SEM revealed well-bonded adhesive-dentin interfaces with numerous resin tags. MDPB or NAg each greatly reduced biofilm viability and acid production, compared to control. Dual agents MDPB+NAg had a much stronger effect than either agent alone (pantibacterial primers (p>0.1). Conclusions The method of using dual agents MDPB+NAg in the primer yielded potent antibacterial properties. Hence, this method may be promising to combat residual bacteria in tooth cavity and invading bacteria at the margins. The dual agents MDPB+NAg may have wide applicability to other adhesives, composites, sealants and cements to inhibit biofilms and caries. PMID:23402889

  8. Hazelnut (Corylus avellana L. Shells Extract: Phenolic Composition, Antioxidant Effect and Cytotoxic Activity on Human Cancer Cell Lines

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    Tiziana Esposito

    2017-02-01

    Full Text Available Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE/g of extract. Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%–2.93%, w/w. The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH (EC50 = 31.7 μg/mL with respect to α-tocopherol EC50 = 10.1 μg/mL, and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 μg/mL, respectively. The expression of cleaved forms of caspase-3 and poly(ADP-ribose polymerase-1 (PARP-1 suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28 and human cervical cancer (HeLa cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin, and phenol derivatives (gallic acid, showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.

  9. Surface reactivity, cytotoxic, and morphological transforming effects of diatomaceous Earth products in Syrian hamster embryo cells.

    Science.gov (United States)

    Elias, Zoé; Poirot, Odile; Fenoglio, Ivana; Ghiazza, Mara; Danière, Marie-Céleste; Terzetti, Francine; Darne, Christian; Coulais, Catherine; Matekovits, Ildiko; Fubini, Bice

    2006-06-01

    In order to evaluate the effect of thermal treatments on the surface reactivity and carcinogenic potential of diatomaceous earth (DE) products, the physicochemical features of some specimens--derived by heating the same original material--were compared with their cytotoxic and transforming potency. The samples were an untreated DE (amorphous) progressively heated in the laboratory at 900 degrees C (DE 900) and 1200 degrees C (DE 1200) and a commercial product manufactured from the same DE (Chd) from which the finer fraction (reactive oxygen species, and for their cytotoxic and transforming potencies in Syrian hamster embryo (SHE) cells. X-ray diffractometry showed that DE 900, like DE, was still amorphous, whereas DE 1200 as well as the commercial product (Chd) were partially crystallized into cristobalite. The ability of the dust to release hydroxyl (*OH) radicals in the presence of hydrogen peroxide, as revealed by the spin-trapping technique, was as follows: Chd-F, DE 1200 > Chd > DE 900 > DE, suggesting that on heating, the surface acquires a higher potential for free radical release. Most of the silica samples generated COO* radicals from the formate ion, following homolytic rupture of the carbon-hydrogen bond, in the presence of ascorbic acid. A concentration-dependent decrease in cell proliferation and colony-forming efficiency was observed in SHE cultures treated with Chd-F, Chd, and DE. Heating abolished DE cytotoxicity but conferred a transforming ability to thermal treated particles. DE was the only sample that did not induce morphological transformation of cells. According to their transformation capacity, the samples were classified as follows: Chd-F > Chd, DE 1200 > DE 900 > DE. Taken together, the reported results suggest that (1) the transforming potential of a biogenic amorphous silica is related to the thermal treatment that transforms the original structure in cristobalite and generates surface active sites; (2) the reactivity of samples in

  10. Antibacterial and Cytotoxic Activities of Acacia nilotica Lam ...

    African Journals Online (AJOL)

    The bactericidal activity was heat-resistant and showed minimal cytotoxic effects on human brain microvascular endothelial cells. FPLC revealed eight peaks, with three of them representing compounds that had maximum bactericidal activity against all the tested isolates, but showed < 30 % host cell cytotoxicity. Conclusion: ...

  11. [Cytotoxic effect in human colon of enterohemorrhagic Escherichia coli isolated from calves with bloody diarrhea].

    Science.gov (United States)

    Pistone Creydt, V; Venzano, A; Vilte, D A; Mercado, E C; Ibarra, C

    2005-01-01

    Shiga toxin-producing E. coli (STEC) is one of the most important emergent pathogen in foods, being its main reservoir bovine cattle. STEC can cause diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome. The present work have studied the cytotoxic action in human colon of cultures of two STEC strains isolated from faeces of calves with bloody diarrhea. Colonic mucosa was mounted as a diaphragm in a Ussing chamber and incubated with the cultures of pathogenic strains. Net water flow (Jw) decreased and the short-circuit current (Isc) increased significantly (p < 0.01) compared to negative control. Tissues showed an erosion of the mucose, epithelial exfoliation, and presence of pseudo-membranes in the lumen. Mild circulatory lesions were observed in the lamina propia. A moderate neutrophils infiltration was observed in the lumen and into the epithelial cells. Colonic crypts were not disrupted. Both experimental strains caused a similar lesion on colon tissues. This is the first study that shows that cultures of STEC strains isolated from bovine cattle produce cytotoxic effects in vitro in human colon.

  12. Cytotoxic effect of silver nanoparticles synthesized from Padina tetrastromatica on breast cancer cell line

    Science.gov (United States)

    Gnana Selvi, B. Clara; Madhavan, J.; Santhanam, Amutha

    2016-09-01

    In recent years researchers were attracted towards marine sources due to the presence of active components in it. Seaweeds were widely used in pharmaceutical research for their known biological activities. The biological synthesis method of silver nanoparticles (AgNPs) using Padina tetrastromatica seaweed extract and their cytotoxicity against breast cancer MCF-7 cells was reported in this study. The synthesized AgNPs using seaweed extract were subjected to x-ray diffraction, UV-visible spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscope, energy dispersive x-ray, zeta potential to elucidate the structural, morphology, size as well as surface potential parameters. An absorption peak at 430 nm in UV-visible spectrum reveals the excitation and surface plasmon resonance of AgNPs. FE-SEM micrographs exhibits the biosynthesized AgNPs, which are pre-dominantly round shaped and the size ranges between 40-50 nm. The zeta potential value of -27.6 mV confirms the stable nature of biosynthesized silver nanoparticles. Furthermore, the biological synthesized Ag NPs exhibited a dose-dependent cytotoxicity against human breast cancer cell (MCF-7) and the inhibitory concentration (IC50) was found for AgNPs against MCF-7 at 24 h incubation. Biological method of synthesizing silver nanoparticles shows a environmental friendly property which helps in effective electrifying usage in many fields.

  13. Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line.

    Directory of Open Access Journals (Sweden)

    Refilwe P Molatlhegi

    Full Text Available Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z-4-[9-ethyl-9aH-carbazol-3-yl amino] pent-3-en-2-one (ECAP to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT, lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9 assay and flow cytometry was used to measure phosphatidylserine (PS externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD, Hsp70 (p < 0.02 and Bcl-2 (p < 0.0006, thereby up-regulating reactive oxygen species (ROS production. This resulted in DNA damage (p < 0.0001, up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.

  14. New ventures in the genotoxic and cytotoxic effects of macrocyclic lactones, abamectin and ivermectin.

    Science.gov (United States)

    Molinari, G; Soloneski, S; Larramendy, M L

    2010-01-01

    Abamectin and Ivermectin are 2 closely related members of the Avermectin family of 16-membered macrocyclic lactones derived from the actinomycete Streptomyces avermectinius which exhibit extraordinary anthelmintic activity. They are used worldwide in veterinary and human medicine as well as in agriculture. In the present review we summarized the results published so far for estimating the genotoxicity and cytotoxicity exerted by both compounds in several cellular systems. Although both compounds do not induce in vitro and in vivo gene mutations in either bacterial or mammalian cells, there is no concrete evidence of a clear clastogenic effect exerted both in vitro and in vivo in mammalian cells. However, reports indicating that both anthelmintic agents are able to induce single DNA-strand breaks in vitro and inhibit cell growth either in vitro or in in vivo bioassays, are scarce. Taking into account the similarity of the genotoxicity and cytotoxicity exerted by both antibiotics, and that only Abamectin has been classified so far as a class II toxicity pesticide by the EPA, the necessity of reconsideration for a further hazard evaluation of Ivermectin by an international regulatory agency(ies) is strongly recommended. Copyright 2010 S. Karger AG, Basel.

  15. Effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine-induced cytotoxicity in PC12 cells.

    Science.gov (United States)

    Park, Hyun Jin; Lee, Kyung Sook; Zhao, Ting Ting; Lee, Kyung Eun; Lee, Myung Koo

    2017-05-01

    This study investigated the effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in rat adrenal pheochromocytoma (PC12) cells. Treatment with asarinin (25-50 μM) increased intracellular dopamine levels and enhanced L-DOPA-induced increases in dopamine levels. Asarinin (25 μM) induced cyclic AMP-dependent protein kinase A (PKA) signaling, leading to increased cyclic AMP-response element binding protein (CREB) and tyrosine hydroxylase (TH) phosphorylation, which in turn stimulated dopamine production. Asarinin (25 μM) also activated transient phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Bad phosphorylation at Ser 112, both of which have been shown to promote cell survival. In contrast, asarinin (25 μM) inhibited sustained ERK1/2, Bax, c-Jun N-terminal kinase (JNK1/2) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation and caspase-3 activity, which were induced by 6-OHDA (100 μM). These results suggest that asarinin induces dopamine biosynthesis via activation of the PKA-CREB-TH system and protects against 6-OHDA-induced cytotoxicity by inhibiting the sustained activation of the ERK-p38MAPK-JNK1/2-caspase-3 system in PC12 cells.

  16. Effects of copper ions on DNA binding and cytotoxic activity of a chiral salicylidene Schiff base.

    Science.gov (United States)

    Fei, Bao-Li; Xu, Wu-Shuang; Tao, Hui-Wen; Li, Wen; Zhang, Yu; Long, Jian-Ying; Liu, Qing-Bo; Xia, Bing; Sun, Wei-Yin

    2014-03-05

    A chiral Schiff base HL N-(5-bromo-salicylaldehyde)dehydroabietylamine (1) and its chiral dinuclear copper complex [Cu2L4]·4DMF (2) have been synthesized and fully characterized. The interactions of 1 and 2 with salmon sperm DNA have been investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. Absorption spectral (Kb=3.30 × 10(5)M(-)(1) (1), 6.63 × 10(5)M(-)(1)(2)), emission spectral (Ksv=7.58 × 10(3)M(-)(1) (1), 1.52 × 10(4)M(-)(1) (2)), and viscosity measurements reveal that 1 and 2 interact with DNA through intercalation and 2 exhibits a higher DNA binding ability. In addition, CD study indicates 2 cause a more evident perturbation on the base stacking and helicity of B-DNA upon binding to it. In fluorimetric studies, the enthalpy (ΔH>0) and entropy (ΔS>0) changes of the reactions between the compounds with DNA demonstrate hydrophobic interactions. 1 and 2 were also screened for their cytotoxic ability and 2 demonstrates higher growth inhibition of the selected cancer cells at concentration of 50 μM, this result is identical with their DNA binding ability order. All the experimental results show that the involvement of Cu (II) centers has some interesting effect on DNA binding ability and cytotoxicity of the chiral Schiff base. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. In vitro analysis of the cytotoxicity and the antimicrobial effect of four endodontic sealers

    Directory of Open Access Journals (Sweden)

    Willershausen Ines

    2011-08-01

    Full Text Available Abstract Introduction The aim of this study was to investigate in vitro the cytotoxicity and antibacterial properties of four different endodontic sealers using human periodontal ligament fibroblast cell proliferation and visual analysis of growth inhibition. Methods A silicone (GuttaFlow, silicate (EndoSequence BC, zinc oxide eugenol (Pulp Canal Sealer EWT and epoxy resin (AH Plus Jet based sealer were incubated with PDL fibroblasts (104 cells/ml, n = 6 up to 96 h. Cell proliferation (RFU was determined by means of the Alamar Blue assay. Cell growth and morphology was visualized by means of fluorescent dyes. Possible antibacterial properties of the different sealers were visualized by means of SEM (Enterococcus faecalis; Parvimonas micra. Results Fibroblast proliferation depended on sealer and cultivation time. After 72 and 96 h GuttaFlow and EndoSequence BC showed relatively non-cytotoxic reactions, while Pulp Canal Sealer EWT and AH Plus Jet caused a significant decrease of cell proliferation (p P. micra was found, whereas GuttaFlow showed a weak, Pulp Canal Sealer EWT and AH Plus Jet extensive growth inhibition. Also, no antibacterial effect of GuttaFlow, EndoSequence BC or AH Plus Jet to E. faecalis could be detected. Conclusions These in vitro findings reveal that GuttaFlow and EndoSequence BC can be considered as biocompatible sealing materials. However, prior to their clinical employment, studies regarding their sealing properties also need to be considered.

  18. Quantum dot cytotoxicity in vitro: an investigation into the cytotoxic effects of a series of different surface chemistries and their core/shell materials.

    Science.gov (United States)

    Clift, Martin J D; Varet, Julia; Hankin, Steven M; Brownlee, Bill; Davidson, Alan M; Brandenberger, Christina; Rothen-Rutishauser, Barbara; Brown, David M; Stone, Vicki

    2011-12-01

    The aim of this study was to assess the effects of a series of different surface coated quantum dots (QDs) (organic, carboxylated [COOH] and amino [NH₂] polytethylene glycol [PEG]) on J774.A1 macrophage cell viability and to further determine which part of the QDs cause such toxicity. Cytotoxic examination (MTT assay and LDH release) showed organic QDs to induce significant cytotoxicity up to 48 h, even at a low particle concentration (20 nM), whilst both COOH and NH₂ (PEG) QDs caused reduced cell viability and cell membrane permeability after 24 and 48 h exposure at 80 nM. Subsequent analysis of the elements that constitute the QD core, core/shell and (organic QD) surface coating showed that the surface coating drives QD toxicity. Elemental analysis (ICP-AES) after 48 h, however, also observed a release of Cd from organic QDs. In conclusion, both the specific surface coating and core material can have a significant impact on QD toxicity.

  19. Cytotoxicity studies of AZ31D alloy and the effects of carbon dioxide on its biodegradation behavior in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiali, E-mail: wangjialicsu@yahoo.cn [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR (China); Qin, Ling [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR (China); Wang, Kai [School of Humanities and Social Sciences, Hunan University of Chinese Medicine, Changsha 410208 (China); Wang, Jue; Yue, Ye [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Li, Yangde [Guangdong Innovation Team for Biodegradable Magnesium and Medical Implants, E-ande, Dongguan 523660 (China); Tang, Jian [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Li, Weirong [Guangdong Innovation Team for Biodegradable Magnesium and Medical Implants, E-ande, Dongguan 523660 (China)

    2013-10-01

    Magnesium alloys have been advocated as potential artificial bone materials due to their biocompatibility and biodegradability. The understanding of their corrosive mechanism in physiological environments is therefore essential for making application-orientated designs. Thus, this in vitro study was designed to assess the effects of CO{sub 2} on corrosive behavior of AZ31D to mimic in vivo special ingredient. Electrochemical technologies accompanied with Scanning electron microscope, Fourier transform infrared, X-ray diffraction, Energy dispersive spectroscopy and hydrogen evolution measurement were employed to analyze corrosive rates and mechanisms of AZ31D. Moreover, the biocompatibility of AZ31D was assessed with a direct cell attachment assay and an indirect cytotoxicity test in different diluted extracts. The ion concentrations in extracts were measured using inductively coupled plasma mass spectrometry to offer explanations on the differences of cell viability in the indirect test. The results of the direct cytotoxicity assay showed that the corrosive rate of AZ31D was too rapid to allow for cell adhesion. Extracts diluted less than 20 times would cause adverse effects on cell proliferation, likely due to excessive ions and gas release. Moreover, the presence of CO{sub 2} did not cause significant differences on corrosive behavior of AZ31D according to the results of electrochemical testing and hydrogen evolution measurement. This might be caused by the simultaneous process of precipitation and dissolution of MgCO{sub 3} due to the penetration role of CO{sub 2}. This analysis of corrosive atmospheres on the degradation behavior of magnesium alloys would contribute to the design of more scientific in vitro testing systems in the future. - Highlights: • We evaluate the effects of CO{sub 2} on corrosion behavior of magnesium alloys. • We assess the feasibility of commercial AZ31D alloy as potential implants. • CO{sub 2} is not the key factor to minimize

  20. Aminosilane Functionalization and Cytotoxicity Effects of Upconversion Nanoparticles Y2O3 and Gd2O3 Co-doped with Yb3+and Er3+

    Directory of Open Access Journals (Sweden)

    Dalia Holanda Chavez

    2016-01-01

    trazolium. The assays show that some concentrations of bare UCNPs were cytotoxic for cervical adenocarcinoma cells (HeLa; however, for human colorectal adenocarcino‐ ma all UCNPs are non-cytotoxic. After UCNPs functional‐ ization with silica-aminosilane (APTES/TEOS, all of the nanoparticles tested were found to be non-cytotoxic for both cell lines. The UCNPs functionalized in this work can be further conjugated with specific ligands and used as biolabels for detection of cancer cells.

  1. [Interaction of intermittent fasting on the cytotoxic effects of nickel in rats at puberty].

    Science.gov (United States)

    Hfaïedh, Najla; Allaqui, Mohamed Salah; Croute, Françoise; Soleilhavoup, Jean-Pierre; Jammoussi, Kamel; Makni Ayadi, Fatma; Kammoun, Abdelaziz; El Feki, Abdelfattah

    2005-07-01

    This study has been undertaken with the aim of determining if intermittent fasting can be considered as a malnutrition that amplifies, according to numerous authors, the cytotoxic effects of environmental pollutants. We have used 200 male and female rats of 'Wistar' descent (BW approximately 180 g). These rats are distributed into two groups: some nourished daily (N) and others nourished one day over two (J) during a month. By the end of this month, each group is itself split into two subgroups, the first one receiving tap water as drinkable water (group NO and JO); the other one receiving the water enriched by the chloride of nickel at the rate of 100 mg NiCl2 per litre (groups NNi and JNi). Intermittent fasting goes on parallel to treatment during 2, 4, 10, 16, 30 and 60 days. For the exploration of the protein of stress (HSP) and of the metallothioneines (MT), the nickel is administered by injection at the rate of 4 mg NiCl2 per kg during 1 and 5 days. Our results show that the mineral seric and renal balance does not vary in conditions of intermittent fasting compared with conditions of normal nutrition. Our study show than that nickel induced a renal deficiency by decreasing the creatinemia and uraemia rate, which is confirmed by the histological study, and induced a decrease in the induction of the HSP73 and in the synthesis of the (MT). The association of nickel with intermittent fasting would inhibit these effects. In conclusion, intermittent fasting does not manifest itself as a malnutrition that amplifies the nickel's effects. Nevertheless, it seems that the calorific lack provoked by intermittent fasting is beneficial to the body by increasing its performances against the cytotoxic effects induced by nickel.

  2. Digital holographic microscopy as multimodal read out for in vitro nanomaterial cytotoxicity testing

    Science.gov (United States)

    Mues, Sarah; Ketelhut, Steffi; Kemper, Björn; Schnekenburger, Jürgen

    2017-07-01

    Digital holographic microscopy (DHM) was used as multimodal optical method for nanomaterial toxicity testing that overcomes the limitations and assay disturbances of conventional in vitro assays based on absorbance or fluorescence read outs.

  3. Effect of reduced exposure times on the cytotoxicity of resin luting cements cured by high-power led

    Directory of Open Access Journals (Sweden)

    Gulfem Ergun

    2011-06-01

    Full Text Available OBJECTIVE: Applications of resin luting agents and high-power light-emitting diodes (LED light-curing units (LCUs have increased considerably over the last few years. However, it is not clear whether the effect of reduced exposure time on cytotoxicity of such products have adequate biocompatibility to meet clinical success. This study aimed at assessing the effect of reduced curing time of five resin luting cements (RLCs polymerized by high-power LED curing unit on the viability of a cell of L-929 fibroblast cells. MATERIAL AND METHODS: Disc-shaped samples were prepared in polytetrafluoroethylene moulds with cylindrical cavities. The samples were irradiated from the top through the ceramic discs and acetate strips using LED LCU for 20 s (50% of the manufacturer's recommended exposure time and 40 s (100% exposure time. After curing, the samples were transferred into a culture medium for 24 h. The eluates were obtained and pipetted onto L-929 fibroblast cultures (3x10(4 per well and incubated for evaluating after 24 h. Measurements were performed by dimethylthiazol diphenyltetrazolium assay. Statistical significance was determined by two-way ANOVA and two independent samples were compared by t-test. RESULTS: Results showed that eluates of most of the materials polymerized for 20 s (except Rely X Unicem and Illusion reduced to a higher extent cell viability compared to samples of the same materials polymerized for 40 s. Illusion exhibited the least cytotoxicity for 20 s exposure time compared to the control (culture without samples followed by Rely X Unicem and Rely X ARC (90.81%, 88.90%, and 83.11%, respectively. For Rely X ARC, Duolink and Lute-It 40 s exposure time was better (t=-1.262 p=0,276; t=-9.399 p=0.001; and t=-20.418 p<0.001, respectively. CONCLUSION: The results of this study suggest that reduction of curing time significantly enhances the cytotoxicity of the studied resin cement materials, therefore compromising their clinical

  4. Effect of reduced exposure times on the cytotoxicity of resin luting cements cured by high-power led

    Science.gov (United States)

    ERGUN, Gulfem; EGILMEZ, Ferhan; YILMAZ, Sukran

    2011-01-01

    Objective Applications of resin luting agents and high-power light-emitting diodes (LED) light-curing units (LCUs) have increased considerably over the last few years. However, it is not clear whether the effect of reduced exposure time on cytotoxicity of such products have adequate biocompatibility to meet clinical success. This study aimed at assessing the effect of reduced curing time of five resin luting cements (RLCs) polymerized by high-power LED curing unit on the viability of a cell of L-929 fibroblast cells. Material and Methods Disc-shaped samples were prepared in polytetrafluoroethylene moulds with cylindrical cavities. The samples were irradiated from the top through the ceramic discs and acetate strips using LED LCU for 20 s (50% of the manufacturer's recommended exposure time) and 40 s (100% exposure time). After curing, the samples were transferred into a culture medium for 24 h. The eluates were obtained and pipetted onto L-929 fibroblast cultures (3x104 per well) and incubated for evaluating after 24 h. Measurements were performed by dimethylthiazol diphenyltetrazolium assay. Statistical significance was determined by two-way ANOVA and two independent samples were compared by t-test. Results Results showed that eluates of most of the materials polymerized for 20 s (except Rely X Unicem and Illusion) reduced to a higher extent cell viability compared to samples of the same materials polymerized for 40 s. Illusion exhibited the least cytotoxicity for 20 s exposure time compared to the control (culture without samples) followed by Rely X Unicem and Rely X ARC (90.81%, 88.90%, and 83.11%, respectively). For Rely X ARC, Duolink and Lute-It 40 s exposure time was better (t=-1.262 p=0,276; t=-9.399 p=0.001; and t=-20.418 p<0.001, respectively). Conclusion The results of this study suggest that reduction of curing time significantly enhances the cytotoxicity of the studied resin cement materials, therefore compromising their clinical performance. PMID

  5. Evaluation of cytotoxic action of antihistamines – desloratadine and loratadine – using bulls spermatozoa as a test object

    Directory of Open Access Journals (Sweden)

    O. Kuzminov

    2014-02-01

    Full Text Available Antihistamines with active ingredients of loratadine and desloratadine are produced by Ukrainian pharmaceutical industry. According to the law, ther are assessed for their potential danger to human health and the environment, including alternative test objects. Evaluation has been carried out with regard to cytotoxic effect of pharmacological substances (loratadine and desloratadine using the bull sperm suspension as test objects, standardized and highly sensitive to toxic substances. Sperm was divided into the control sample (dissolved by phosphate-buffered saline and the investigated sample. Loratadine was added to phosphate-buffered saline in doses of 1/500 LD50 (12.3 mg, 1/100 LD50 (61.5 mg and LD50 (6150 mg. Desloratadine doses were 1/500 LD50 (1.25 mg, 1/100 LD50 (6.25 mg and LD50 (625 mg. Survival of spermatozoa was defined until termination of rectilinear forward movement in sperm intacted at +2…+5 °C. Respiratory activity (ex tempore was defined in 1.0 ml thermostated cell (temperature of 38.5 °C by polarography with the automatic registration of process flow by potentiometer; restorative activity was defined potentiometrically, using the open microelectrodes that were inserted in thermostated polarographic cell. Survival of spermatozoa in the sperm under the impact of loratadine in doses of 1/500 LD50 and 1/100 LD50 is respectively 136.0 ± 26.2 hours and 144.0 ± 19.6 hours. Adding LD50 dose of loratadine reduced survival to 112.0 ± 26.2 hours, which is lower than the control (160.0 ± 26.1 hours, respectively, by 10.0–15.0 and 30.0%. Loratadine reduces the respiratory activity of sperm: in the dose of 1/500 LD50 by 20.5%, in the dose of 1/100 LD50 – by 43.6%, and that of 100 LD50 – by 61.5% compared to the control. Restorative sperm activity under the impact of the loratadine reduced by 84.0% (dose of 1/500 LD50, 98.0% (dose of 1/100 LD50, 80.0% (dose LD50 compared to controls. The survival of spermatozoa in the sperm

  6. Biological effects of a de novo designed myxoma virus peptide analogue: evaluation of cytotoxicity on tumor cells.

    Science.gov (United States)

    Istivan, Taghrid S; Pirogova, Elena; Gan, Emily; Almansour, Nahlah M; Coloe, Peter J; Cosic, Irena

    2011-01-01

    The Resonant Recognition Model (RRM) is a physico-mathematical model that interprets protein sequence linear information using digital signal processing methods. In this study the RRM concept was employed for structure-function analysis of myxoma virus (MV) proteins and the design of a short bioactive therapeutic peptide with MV-like antitumor/cytotoxic activity. The analogue RRM-MV was designed by RRM as a linear 18 aa 2.3 kDa peptide. The biological activity of this computationally designed peptide analogue against cancer and normal cell lines was investigated. The cellular cytotoxicity effects were confirmed by confocal immunofluorescence microscopy, by measuring the levels of cytoplasmic lactate dehydrogenase (LDH) and by Prestoblue cell viability assay for up to 72 hours in peptide treated and non-treated cell cultures. Our results revealed that RRM-MV induced a significant dose and time-dependent cytotoxic effect on murine and human cancer cell lines. Yet, when normal murine cell lines were similarly treated with RRM-MV, no cytotoxic effects were observed. Furthermore, the non-bioactive RRM designed peptide RRM-C produced negligible cytotoxic effects on these cancer and normal cell lines when used at similar concentrations. The presence/absence of phosphorylated Akt activity in B16F0 mouse melanoma cells was assessed to indicate the possible apoptosis signalling pathway that could be affected by the peptide treatment. So far, Akt activity did not seem to be significantly affected by RRM-MV as is the case for the original viral protein. Our findings indicate the successful application of the RRM concept to design a bioactive peptide analogue (RRM-MV) with cytotoxic effects on tumor cells only. This 2.345 kDa peptide analogue to a 49 kDa viral protein may be suitable to be developed as a potential cancer therapeutic. These results also open a new direction to the rational design of therapeutic agents for future cancer treatment.

  7. Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect.

    Science.gov (United States)

    Panáček, Aleš; Smékalová, Monika; Kilianová, Martina; Prucek, Robert; Bogdanová, Kateřina; Večeřová, Renata; Kolář, Milan; Havrdová, Markéta; Płaza, Grażyna Anna; Chojniak, Joanna; Zbořil, Radek; Kvítek, Libor

    2015-12-28

    The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.

  8. Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect

    Directory of Open Access Journals (Sweden)

    Aleš Panáček

    2015-12-01

    Full Text Available The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.

  9. pH-dependent cytotoxic effects of extracts of the marine sponge Polymastia janeirensis on cancer cell lines.

    Science.gov (United States)

    Biegelmeyer, Renata; Schröder, Rafael; Rambo, Douglas F; Dresch, Roger R; Carraro, João L F; Mothes B, Beatriz; Moreira, José Cláudio F; da Frota Junior, Mario L C; Henriques, Amélia T

    2016-02-09

    The purpose of this work was to study the cytotoxic effects of marine sponge Polymastia janeirensis, which has been observed in the field to release an orange substance that is toxic to fish. The result showed that aqueous extract (pH 7.0) was highly cytotoxic to glioma (U87) and neuroblastoma (SHSY5Y) cancer cell lines (IC 50  antioxidant and procoagulant (decreased the clotting time by 1.7-fold) activities. Interestingly, the cytotoxic effects were pH-dependent since the viability of the cancer cells was not affected with the extract (pH 5.5). The close similarity between the aqueous extract (pH 7.0) and the orange liquid that is released by the sponge indicates that this potential chemical defence of P. janeirensis deserves further investigation.

  10. Analogues of the epoxy resin monomer diglycidyl ether of bisphenol F: effects on contact allergenic potency and cytotoxicity.

    Science.gov (United States)

    O'Boyle, Niamh M; Delaine, Tamara; Luthman, Kristina; Natsch, Andreas; Karlberg, Ann-Therese

    2012-11-19

    Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used as components in epoxy resin thermosetting products. They are known to cause occupational and nonoccupational allergic contact dermatitis. The aim of this study is to investigate analogues of DGEBF with regard to contact allergy and cytotoxicity. A comprehensive knowledge of the structural features that contribute to the allergenic and cytotoxic effects of DGEBF will guide the development of future novel epoxy resin systems with reduced health hazards for those coming into contact with them. It was found that the allergenic effects of DGEBF were dependent on its terminal epoxide groups. In contrast, it was found that the cytotoxicity in monolayer cell culture was dependent not only on the presence of epoxide groups but also on other structural features.

  11. Green synthesis of graphene and its cytotoxic effects in human breast cancer cells.

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Han, Jae Woong; Eppakayala, Vasuki; Kim, Jin-Hoi

    2013-01-01

    This paper describes an environmentally friendly ("green") approach for the synthesis of soluble graphene using Bacillus marisflavi biomass as a reducing and stabilizing agent under mild conditions in aqueous solution. In addition, the study reported here investigated the cytotoxicity effects of graphene oxide (GO) and bacterially reduced graphene oxide (B-rGO) on the inhibition of cell viability, reactive oxygen species (ROS) generation, and membrane integrity in human breast cancer cells. The reduction of GO was characterized by ultraviolet-visible spectroscopy. Size distribution was analyzed by dynamic light scattering. Further, X-ray diffraction and high-resolution scanning electron microscopy were used to investigate the crystallinity of graphene and the morphologies of prepared graphene, respectively. The formation of defects further supports the bio-functionalization of graphene, as indicated in the Raman spectrum of B-rGO. Surface morphology and the thickness of the GO and B-rGO were analyzed using atomic force microscopy, while the biocompatibility of GO and B-rGO were investigated using WST-8 assays on MCF-7 cells. Finally, cellular toxicity was evaluated by ROS generation and membrane integrity assays. In this study, we demonstrated an environmentally friendly, cost-effective, and simple method for the preparation of water-soluble graphene using bacterial biomass. This reduction method avoids the use of toxic reagents such as hydrazine and hydrazine hydrate. The synthesized soluble graphene was confirmed using various analytical techniques. Our results suggest that both GO and B-rGO exhibit toxicity to MCF-7 cells in a dose-dependent manner, with a dose > 60 μg/mL exhibiting obvious cytotoxicity effects, such as decreasing cell viability, increasing ROS generation, and releasing of lactate dehydrogenase. We developed a green and a simple approach to produce graphene using bacterial biomass as a reducing and stabilizing agent. The proposed approach

  12. Silver nanoparticles with antimicrobial activities against Streptococcus mutans and their cytotoxic effect

    Energy Technology Data Exchange (ETDEWEB)

    Pérez-Díaz, Mario Alberto [Facultad de Ciencias Químicas, UASLP, Álvaro Obregón 64, San Luis Potosí (Mexico); Boegli, Laura; James, Garth [Center for Biofilm Engineering, Montana State University, Bozeman, MT (United States); Velasquillo, Cristina; Sánchez-Sánchez, Roberto [Laboratorio de Biotecnología, Instituto Nacional de Rehabilitación (Mexico); Martínez-Martínez, Rita-Elizabeth; Martínez-Castañón, Gabriel Alejandro [Facultad de Estomatología, Universidad Autónoma de San Luis Potosí (Mexico); Martinez-Gutierrez, Fidel, E-mail: fidel@uaslp.mx [Facultad de Ciencias Químicas, UASLP, Álvaro Obregón 64, San Luis Potosí (Mexico)

    2015-10-01

    Microbial resistance represents a challenge for the scientific community to develop new bioactive compounds. The goal of this research was to evaluate the antimicrobial activity of silver nanoparticles (AgNPs) against a clinical isolate of Streptococcus mutans, antibiofilm activity against mature S. mutans biofilms and the compatibility with human fibroblasts. The antimicrobial activity of AgNPs against the planktonic clinical isolate was size and concentration dependent, with smaller AgNPs having a lower minimum inhibitory concentration. A reduction of 2.3 log in the number of colony-forming units of S. mutans was observed when biofilms grown in a CDC reactor were exposed to 100 ppm of AgNPs of 9.5 ± 1.1 nm. However, AgNPs at high concentrations (> 10 ppm) showed a cytotoxic effect upon human dermal fibroblasts. AgNPs effectively inhibited the growth of a planktonic S. mutans clinical isolate and killed established S. mutans biofilms, which suggests that AgNPs could be used for prevention and treatment of dental caries. Further research and development are necessary to translate this technology into therapeutic and preventive strategies. - Highlights: • Biological activities of silver nanoparticles for dental caries purposes • Antimicrobial activity of AgNPs on planktonic cell was size and concentration dependent. • Reduction in the S. mutans biofilm formation was statistically significant. • AgNPs at high concentrations showed a cytotoxic effect upon human dermal fibroblasts. • AgNPs could be used for prevention and treatment of dental caries.

  13. Schedule-Dependent Antiangiogenic and Cytotoxic Effects of Chemotherapy on Vascular Endothelial and Retinoblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Ursula Winter

    Full Text Available Current treatment of retinoblastoma involves using the maximum dose of chemotherapy that induces tumor control and is tolerated by patients. The impact of dose and schedule on the cytotoxicity of chemotherapy has not been studied. Our aim was to gain insight into the cytotoxic and antiangiogenic effect of the treatment scheme of chemotherapy used in retinoblastoma by means of different in vitro models and to evaluate potential effects on multi-drug resistance proteins. Two commercial and two patient-derived retinoblastoma cell types and two human vascular endothelial cell types were exposed to increasing concentrations of melphalan or topotecan in a conventional (single exposure or metronomic (7-day continuous exposure treatment scheme. The concentration of chemotherapy causing a 50% decrease in cell proliferation (IC50 was determined by MTT and induction of apoptosis was evaluated by flow cytometry. Expression of ABCB1, ABCG2 and ABCC1 after conventional or metronomic treatments was assessed by RT-qPCR. We also evaluated the in vivo response to conventional (0.6 mg/kg once a week for 2 weeks and metronomic (5 days a week for 2 weeks topotecan in a retinoblastoma xenograft model. Melphalan and topotecan were cytotoxic to both retinoblastoma and endothelial cells after conventional and metronomic treatments. A significant decrease in the IC50 (median, 13-fold; range: 3-23 was observed following metronomic chemotherapy treatment in retinoblastoma and endothelial cell types compared to conventional treatment (p0.05. In mice, continuous topotecan lead to significantly lower tumor volumes compared to conventional treatment after 14 days of treatment (p<0.05. Continuous exposure to melphalan or topotecan increased the chemosensitivity of retinoblastoma and endothelial cells to both chemotherapy agents with lower IC50 values compared to short-term treatment. These findings were validated in an in vivo model. None of the dosing modalities induced

  14. Neurotoxic, cytotoxic, apoptotic and antiproliferative effects of some marine algae extracts on the NA2B cell line.

    Science.gov (United States)

    Kurt, O; Özdal-Kurt, F; Akçora, C M; Özkut, M; Tuğlu, M I

    2018-02-01

    Oxidative stress contributes to cancer pathologies and to apoptosis. Marine algae exhibit cytotoxic, antiproliferative and apoptotic effects; their metabolites have been used to treat many types of cancer. We investigated in culture extracts of Petalonia fascia, Jania longifurca and Halimeda tuna to determine their effects on mouse neuroblastoma cell line, NA2B. NA2B cells were treated with algae extracts, and the survival and proliferation of NA2B cells were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of algae extracts on oxidative stress in NA2B cells also were investigated using nitric oxide synthase (NOS) immunocytochemistry and apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling. We observed significant neurite inhibition with moderate damage by the neurotoxicity-screening test (NST) at IC 50 dilutions of the extracts. MTT demonstrated that J. longifurca extracts were more toxic than P. fascia and H. tuna extracts. We found an increase of endothelial and inducible NOS immunostaining for oxidative stress and TUNEL analysis revealed increased apoptosis after application of extract. Our findings suggest that the algae we tested may have potential use for treatment of cancer.

  15. Singlet oxygen mediated DNA degradation by copper nanoparticles: potential towards cytotoxic effect on cancer cells

    Science.gov (United States)

    2011-01-01

    The DNA degradation potential and anti-cancer activities of copper nanoparticles of 4-5 nm size are reported. A dose dependent degradation of isolated DNA molecules by copper nanoparticles through generation of singlet oxygen was observed. Singlet oxygen scavengers such as sodium azide and Tris [hydroxyl methyl] amino methane were able to prevent the DNA degradation action of copper nanoparticles confirming the involvement of activated oxygen species in the degradation process. Additionally, it was observed that the copper nanoparticles are able to exert cytotoxic effect towards U937 and Hela cells of human histiocytic lymphoma and human cervical cancer origins, respectively by inducing apoptosis. The growth characteristics of U937 and Hela cells were studied applying various concentrations of the copper nanoparticles. PMID:21439072

  16. Antioxidant, antibacterial and cytotoxic effects of the phytochemicals of whole Leucas aspera extract

    Science.gov (United States)

    Rahman, Md Atiar; Islam, Md Saiful

    2013-01-01

    Objective To investigate the antioxidant, antibacterial and cytotoxic activity of whole Leucas aspera (Labiatae) (L. aspera) alcoholic extract. Methods Whole L. aspera powder was extracted by absolute ethanol (99.50%). The ethanolic extract was subjected to antioxidant, antibacterial and brine shrimp lethality assay. Results The extract showed potent radical scavenging effect (antioxidant) with IC50 value of (99.58±1.22) µg/mL which was significant (PShigella dysenteriae [(9.00±1.32) mm] and Vibrio cholerae [(9.00±0.66) mm] was observed. In brine shrimp lethality bioassay, the extract showed the LC50 value as (181.68±2.15) µg/mL which was statistically significant (Ppesticidal and various pharmacologic actives. PMID:23620850

  17. New sesquiterpene lactones from Glechoma hederacea L. and their cytotoxic effects on human cancer cell lines.

    Science.gov (United States)

    Kim, JinPyo; Lee, IkSoo; Ha, DoThi; Seo, JeongJu; Min, ByungSun; Yoo, IckDong; Bae, KiHwan

    2011-06-01

    Three new sesquiterpene lactones, 1 α,10 β-epoxy-4-hydroxy-glechoma-5-en-olide (1), 1 β,10 α-epoxy-4,8-dihydroxy-glechoma-5-en-olide (2), and 1 β,10 α;4 α,5 β-diepoxy-8-methoxy-glechoman-8 α,12-olide (3), were isolated from the whole plant of Glechoma hederacea, together with four known sesquiterpene lactones. The structures of the three new sesquiterpene lactones were determined by spectroscopic evidence. Cytotoxic effects of the isolated compounds were examined against MDA-MB-231 (breast), HCT116 (colon), SW620 (colon), and DU145 (prostate) human cancer cell lines. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Effects of sulfate group in red seaweed polysaccharides on anticoagulant activity and cytotoxicity.

    Science.gov (United States)

    Liang, Wanai; Mao, Xuan; Peng, Xiaohui; Tang, Shunqing

    2014-01-30

    In this paper, the structural effects of two main red seaweed polysaccharides (agarose and carrageenan) and their sulfated derivatives on the anticoagulant activity and cytotoxicity were investigated. The substitution position rather than the substitution degree of sulfate groups shows the biggest impact on both the anticoagulant activity and the cell proliferation. Among them, C-2 of 3,6-anhydro-α-d-Galp is the most favorable position for substitution, whereas C-6 of β-d-Galp is the most disadvantageous. Moreover, the secondary structures of glycans also play a key role in biological activities. These demonstrations warrant that the red seaweed polysaccharides should be seriously considered in biomedical applications after carefully tailoring the sulfate groups. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Release of methyl methacrylate from heat-cured and autopolymerized resins: cytotoxicity testing related to residual monomer.

    Science.gov (United States)

    Kedjarune, U; Charoenworaluk, N; Koontongkaew, S

    1999-03-01

    Three heat-cured and three autopolymerized acrylic denture bases with different mixing proportions and/or processing methods were investigated for the amount of residual monomer content and methyl methacrylate (MMA) released into saliva after incubation during the first and second 24 hours after processing. A corresponding range of concentrations of MMA was also used to test for cell cytotoxicity using a culture of human oral fibroblasts. The results showed that the amount of residual monomer was dependent not only on the type of polymerization but also on the amount of liquid in the mixture ratio and the processing method. The acrylic resin that had the lowest residual monomer also released the smallest amount of MMA but resins which have higher residual monomer may not necessarily release higher amounts of MMA. MMA, tested in the same range of concentration as the MMA found leached from acrylic resin in this study, was found to be toxic in the cell culture. Therefore, it is recommended that dentists attempt to reduce the amount of leachable substances before insertion of new dentures. In addition, it is recommended that dentists advise their patients not to wear newly made dentures overnight, as this may cause mucosal irritation from the potential accumulation of leachable substances.

  20. Cytotoxic Effects of Biosynthesized Zinc Oxide Nanoparticles on Murine Cell Lines

    Directory of Open Access Journals (Sweden)

    Farideh Namvar

    2015-01-01

    Full Text Available The aim of this study is to evaluate the in vitro cytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50 values using MTT assay as follows: 21.7 ± 1.3 μg/mL (4T1, 17.45 ± 1.1 μg/mL (CRL-1451, 11.75 ± 0.8 μg/mL (CT-26, and 5.6 ± 0.55 μg/mL (WEHI-3B, respectively. On the other hand, ZnO-NPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3 cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50 of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 μg/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death in WEHI-3 cells. Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer.

  1. Cytotoxic effects of biosynthesized zinc oxide nanoparticles on murine cell lines.

    Science.gov (United States)

    Namvar, Farideh; Rahman, Heshu Sulaiman; Mohamad, Rosfarizan; Azizi, Susan; Tahir, Paridah Mohd; Chartrand, Max Stanley; Yeap, Swee Keong

    2015-01-01

    The aim of this study is to evaluate the in vitro cytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum) aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50 values using MTT assay as follows: 21.7 ± 1.3 μg/mL (4T1), 17.45 ± 1.1 μg/mL (CRL-1451), 11.75 ± 0.8 μg/mL (CT-26), and 5.6 ± 0.55 μg/mL (WEHI-3B), respectively. On the other hand, ZnO-NPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3) cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50 of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 μg/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death in WEHI-3 cells. Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer.

  2. Effective treatment of H838 human non-small cell lung carcinoma with a targeted cytotoxic somatostatin analog, AN-238.

    Science.gov (United States)

    Szereday, Zoltan; Schally, Andrew V; Szepeshazi, Karoly; Bajo, Ana-Maria; Hebert, Francine; Halmos, Gabor; Nagy, Attila

    2003-05-01

    The accumulation of radioactive somatostatin analog [111In]pentetreotide in non-small cell lung cancer (non-SCLC) during scintigraphy of patients provides a rationale for investigating the efficacy of somatostatin receptor-based chemotherapy in non-SCLC. Consequently, in this study, we evaluated the antitumor effects of cytotoxic somatostatin analog AN-238 on H838 human non-SCLC xenografted into nude mice in comparison with its cytotoxic radical, 2-pyrrolinodoxorubicin (AN-201). The expression of messenger RNA (mRNA) for human somatostatin receptor subtypes 2 (hsst2) and 5 (hsst5) in H838 cells, and tumors was also investigated using reverse-transcription polymerase chain reaction (RT-PCR). Somatostatin receptors on H838 tumors were characterized by ligand competition assay using radiolabeled somatostatin analog, RC-160. Three i.v. injections of AN-238 at 150 nmol/kg, given on days 1, 7 and 21, resulted in a significant (p<0.05) tumor growth inhibition, the final tumor volume being 60% smaller than in the controls. The tumor doubling time was also extended significantly (p<0.05) from 9.65+/-0.56 days in the controls to 17.52+/-3.3 days. Only one of 8 mice died due to toxicity. In contrast, cytotoxic radical AN-201 was ineffective and more toxic, killing 2 of 7 animals. mRNA for hsst2 was found in H838 xenografts, but not in H838 cells from which the xenografts originated. Interestingly, H838 cells grown in a special, serum-free medium did express mRNA for hsst2. mRNA for hsst5 was not found in any samples tested. Binding studies demonstrated the presence of high affinity (K(d) = 7.3+/-1.2 nM) binding sites for RC-160 with a mean maximal binding capacity (B(max)) of 953.3+/-45.3 fmol/mg protein. AN-238 at 3.14+/-0.93 nM concentration displaced 50% of radiolabeled RC-160 binding to somatostatin receptors in H838 tumors. Our results indicate that patients with inoperable non-SCLC may benefit from chemotherapy targeted to somatostatin receptors based on AN-238.

  3. Antioxidant properties and cytotoxic effects on human cancer cell lines of aqueous fermented and lipophilic quince (Cydonia oblonga Mill.) preparations.

    Science.gov (United States)

    Pacifico, Severina; Gallicchio, Marialuisa; Fiorentino, Antonio; Fischer, Anna; Meyer, Ulrich; Stintzing, Florian Conrad

    2012-11-01

    In the course of a screening program on quince phytochemicals, two complex preparations were in the focus of the present study, i.e., a lipophilic quince wax extract (QWE) and an aqueous fermented one (QAFE). While the phytochemical composition has been described earlier, the intention of the current investigation was to complement these data with an extensive antioxidant screening of these preparations including their radical scavenging and reductive power as well as their antilipoperoxidative properties. The Quince Aqueous Fermented Extract (QAFE) effectively scavenged the radical target species exhibiting ID(50) values equal to 68.8 μg/mL towards DPPH· and 73.7 μg/mL towards the anion superoxide radical. Quince wax extract (QWE) was more effective at preventing the formation of thiobarbituric reactive species than QAFE exhibiting an ID(50) value equal to 48.9 μg/mL. Moreover the cytotoxic effects towards human HepG2, A549, and HeLa cell lines were evaluated. The two preparations exerted a different effect on the proliferation of the three tested cell lines. Noteworthy, QAFE was almost always more active than QWE but, sometimes, its effects seemed to be strongly dependent on exposure time. Data obtained demonstrate clearly that both hydrophilic and lipophilic quince preparations are non-toxic and exert health-promoting properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Cytotoxic Effect and Constituent Profile of Alkaloid Fractions from Ethanolic Extract of Ficus septica Burm. f. Leaves on T47D Breast Cancer Cells.

    Science.gov (United States)

    Nugroho, Agung Endro; Akbar, Fiki Fatihah; Wiyani, Anggie; Sudarsono

    2015-01-01

    The study aimed to investigate the profile of alkaloids in two ethyl acetate soluble fractions, namely fractions A and B from an ethanolic extract of Ficus septica leaves and cytotoxic effect on T47D breast cancer cells. Preparation of both fractions involved maceration of leaves with 70% (v/v) ethanol, filtration with Al2O3, precipitation with 0.1 N HCl, Mayer reagent, and 0.1 N NaOH, and also partition with ethyl acetate. Qualitative thin layer chromatography (TLC) was conducted to determine the profile of alkaloids in the two fractions, using alkaloid specific reagents such as Dragendorff, sodium nitrite, and Van Urk-Salkowski. Cytotoxic effects of both fractions on T47D cells were evaluated using MTT assay with a concentration series of 1.56; 3.12; 6.25; 12.5; 25 and 50 μg/mL. The TLC test showed that fractions A and B contained alkaloids with Rx values of 0.74 and 0.80 for fraction A and 0.74, 0.84, 0.92 for fraction B with regard to yohimbine using the mobile phase of n-buthanol:glacial acetic acid:distilled water (3:1:1 v/v/v). Moreover, an indole alkaloid was detected with Rx values of 0.80 and 0.84, respectively. Fractions A and B exhibited high cytotoxic effects on T47D cells with IC50 values of 2.57 and 2.73 μg/mL, respectively. In conclusion, overall the results of this study showed that fractions of Ficus septica contain alkaloids including indole alkaloid or its derivatives and possess a cytotoxic effect on T47D cells. This research supports the idea that alkaloids in F. septica have anticancer activity.

  5. Cytotoxicity and inhibitory effects of low-concentration triclosan on adipogenic differentiation of human mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Li-Wu [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Wu, Qiangen [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Green, Bridgett; Nolen, Greg [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Shi, Leming [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); LoSurdo, Jessica [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States); Deng, Helen [Arkansas Department of Health, Little Rock, AR 72205 (United States); Bauer, Steven [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States); Fang, Jia-Long, E-mail: jia-long.fang@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Ning, Baitang, E-mail: baitang.ning@fda.hhs.gov [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)

    2012-07-15

    Humans at all ages are continually exposed to triclosan (TCS), a widely used antimicrobial agent that can be found in many daily hygiene products, such as toothpastes and shampoos; however, the toxicological and biological effects of TCS in the human body after long-term and low-concentration exposure are far from being well understood. In the current study, we investigated the effects of TCS on the differentiation of human mesenchymal stem cells (hMSCs) by measuring the cytotoxicity, morphological changes, lipid accumulation, and the expression of adipocyte differentiation biomarkers during 21-day adipogenesis. Significant cytotoxicity was observed in un-induced hMSCs treated with high-concentration TCS (≥ 5.0 μM TCS), but not with low-concentration treatments (≤ 2.5 μM TCS). TCS inhibited adipocyte differentiation of hMSCs in a concentration-dependent manner in the 0.156 to 2.5 μM range as indicated by morphological changes with Oil Red O staining, which is an index of lipid accumulation. The inhibitory effect was confirmed by a decrease in gene expression of specific adipocyte differentiation biomarkers including adipocyte protein 2, lipoprotein lipase, and adiponectin. Our study demonstrates that TCS inhibits adipocyte differentiation of hMSCs under concentrations that are not cytotoxic and in the range observed in human blood. -- Highlights: ► TCS is cytotoxic to un-induced hMSCs at concentrations ≥ 5.0 μM. ► TCS at concentrations ≤ 2.5 μM is not cytotoxic to induced hMSCs. ► TCS at non-cytotoxic concentrations inhibits lipid formation in induced hMSCs. ► TCS decreases the expression of specific biomarkers of adipocyte differentiation. ► TCS at concentrations observed in human blood inhibits adipogenesis of hMSCs.

  6. Antitumor effect of Ganoderma lucidum : Cytotoxicity and Tumor Growth Delay(1)

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyoung Cheol; Kim, Jung Soo [Chonbuk National University College of Medicine, Chonju (Korea, Republic of); Choi, Dong Seong [Chonju Woosuck Univ., Chonju (Korea, Republic of); Song, Chang Won [Univ. of Minnesota Medical School, Minneapolis (United States)

    1994-10-15

    Purpose: To investigate the effect of aqueous extract of Ganoderma lucidum(G.I.) on the survival of tumor cells in vitro and on the growth of tumors in vivo. Materials and Methods: Dried G.I. was made into powder, extracted with distilled water, filtered and diluted from a maximum concentration of 100 mg/ml in sequence. The cytotoxicity of G.O. in vitro was evaluated from its ability to reduce the clonogenicity of SCK tumor cells. For the tumor growth delay study, about 2x10{sup 5} of SCK tumor cells were subcutaneously inoculated in the legs of A/J mice. The first experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G/I. From the first day after tumor inoculation for 10 days. The second experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G.I. either once a day for 10 days or twice a day for 5 days beginning from the 7th day after tumor inoculation. Results: 1. Cytotoxicity in vitro; survival fraction, as judged from the curve, at G.I. concentration of 0.5, 1,5,10,25,50 and 100 mg/ml were 1.0, 0.74{+-}0.03, 0.18{+-}0.03, 0.15{+-}0.02, 0.006{+-}0.002, 0.015 and 0.0015, respectively. 2. Tumor growth delay in vivo; a) the time required for the mean tumor volume to grow to 1,000mm{sup 3} was 11 days in the control group and 14 days in the experimental group. b) the time required for tumor volume to increase 4 times was 11 days in the control group while it was 10.5 and 12 days in the groups injected with G.I. once a day and twice a day from the 7th day after tumor inoculation respectively. Conclusion: Aqueous extracts of G.I. showed a marked cytotoxicity on the SCK mammary cells in vitro. Tumor growth delay was statistically significant when G.I. injection was started soon after tumor inoculation, but it was not significant when injection was started after the tumors were firmly established.

  7. Cytotoxicity effect of alkaloidal extract from Prosopis juliflora Sw. D.C. (Algaroba pods on glial cells

    Directory of Open Access Journals (Sweden)

    Juliana Bentes Hughes

    2006-12-01

    Full Text Available Prosopis juliflora is largely used for feeding cattle and humans. Neurological signals have been reported in cattle due to intoxication with this plant. In this study, an alkaloidal fraction (AF obtained from P. juliflora pods was tested on astrocyte primary cultures. Astrocytes display physiological functions essential to development, homeostasis and detoxification in the central nervous system (CNS. These cells are known for their role on energetic support and immune response in the CNS. Concentrations between 0.03 to 30 µg/ml AF were assayed for 24 - 72 h. The mitochondrial activity, assayed by MTT test, showed cytotoxicity at 30 µg/ml AF after 24 h. At concentrations ranging between 0.3 - 3 µg/ml, the AF induced an increase on mitochondrial activity, indicating cell reactivity. Immunocytochemistry assay for GFAP cytoskeletal protein, revealed alterations on cell morphology after treatment with 0.3 - 3 µg/ml AF for 72 h. This result corroborates with western blot analysis when cells treated with 0.3 - 3 µg/ml AF for 72 h showed GFAP upregulation. The vimentin expression was not significantly altered in all tested concentrations. These results suggest that alkaloids induce astrocyte reactivity and might be involved in the neurotoxic effects induced by P. juliflora consumption.

  8. Genotoxic and cytotoxic effects of Sunset Yellow and Brilliant Blue, colorant food additives, on human blood lymphocytes.

    Science.gov (United States)

    Kus, Esra; Eroglu, Halil Erhan

    2015-01-01

    The synthetic dyes over fifty are used in many areas including the food industry around the world. Sunset Yellow FCF and Brilliant Blue FCF are used as colorant food additives in many food products. The present study investigated the genotoxic and cytotoxic effects of Sunset Yellow and Brilliant Blue. Genotoxic and cytotoxic activities of the food additives were evaluated in lymphocyte cell cultures using mitotic index, replication index and micronucleus assay. Mitotic index frequencies and replication index values were decreased and micronucleus frequency was increased with increasing concentrations of Sunset Yellow and Brilliant Blue. The changes in mitotic index and micronucleus are statistically significant (p<0.05). The results show that the Sunset Yellow and Brilliant Blue can have cytotoxic and genotoxic potential. It care must be taken when using these materials as a food additive.

  9. Effects on cytotoxicity and antibacterial properties of the incorporations of silver nanoparticles into the surface coating of dental alloys.

    Science.gov (United States)

    Shen, Xiao-Ting; Zhang, Yan-Zhen; Xiao, Fang; Zhu, Jing; Zheng, Xiao-Dong

    2017-07-01

    The aim of this study was to research the changes in cytotoxicity and antibacterial properties after silver nanoparticles (AgNPs) were incorporated into the surface coating of dental alloys. AgNPs were attached to cobalt chromium alloys and pure titanium using a hydrothermal method, according to the reaction: AgNO3+NaBH4→ Ag+1/2H2+1/2B2H6+NaNO3. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate the cytotoxicity of the alloys when in contact with osteogenic precursor cells (MC3T3-E1) from mice and mesenchymal stem cells (BMSC) from rats. The antibacterial properties of dental alloys incorporating three different concentrations (10, 4, and 2 μmol/L) of AgNPs were tested on Staphylococcus aureus (SA) and Streptococcus mutans (MS). High cytotoxicity values were observed for all dental alloys that contained 0% of AgNPs (the control groups). The incorporation of AgNPs reduced cytotoxicity values. No significant difference was observed for antibacterial performance when comparing dental alloys containing AgNPs to the respective control groups. The results demonstrated that the cobalt chromium alloys and pure titanium all had cytotoxicity to MC3T3-E1 and BMSC and that the incorporation of AgNPs could reduce this cytotoxicity. The concentrations of AgNPs adopted in this study were found to have no antibacterial action against SA or MS.

  10. Cytotoxic effects of infusions (tea of Solidago microglossa DC. (Asteraceae on the cell cycle of Allium cepa

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    Margarete Dulce Bagatini

    Full Text Available The medicinal specie Solidago microglossa DC., which is native from South America, is used as infusion (tea for stomach disorders in popular medicine. This study aimed to evaluate the potential cytotoxic effect of these infusions on the cell cycle of Allium cepa. In natura leaves of three populations of this species were used in preparing infusions at two concentrations: 1.75 mg/mL and 14 mg/mL. Onion (Allium cepa root-tip cells were used as test system in in vivo assays. Slides were done through smashing technique. Cells were analyzed in all cell cycles of A. cepa, totalizing 6000 cells for each group of bulbs. The mitotic index (MI was calculated, and the statistical analysis was carried out through the Chi-square test (χ2 = 0.05. The results show that the infusions of S. microglossa at a highest concentration (14 mg/mL caused a significant reduction in the MI compared with control in the studied populations. In concentrations commonly used by people there was a significant increase of MI in relation to controlled populations 1 and 3 and a decrease in population 2. In conclusion, infusions of S. microglossa presented antiproliferative effect at a highest concentration.

  11. EFFECT OF BROMINE ATOMS NUMBER ON THE CYTOTOXICITY OF TWO 2-FURYLETHYLENE DERIVATIVE SUBSTANCES IN NORMAL AND TUMORAL CELL LINES.

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    Oscar Hernández

    2012-01-01

    Full Text Available The study was performed to investigate the effect of bromine atoms number present in two tested substances derivatives of 2-furylethylene on cell proliferation. The substances carrying one or two Br atoms were coded as MA and G1 respectively. The neutral red uptake (NRU assay and mitotic index (MI were used for this purpose. The presence of two bromine atoms on the molecule of G1 inhibited markedly the cytotoxicity of this composite. For CHO cell line, the IC50 values were 256.6 µM for G1 and 134.5 µM for MA; whereas in SK MEL-3 (human melanoma cell line, the IC50 were 413.4 µM and 264.1 µM for G1 and MA respectively. The IC50 values obtained in both cell lines were higher than 100 µM and showed no specificity for tumoral cells. The MI obtained with the G1 composite showed no significant differences with phytohaemoglutinine used as positive control. The anti-proliferative effect and MI were related with the number of bromine atoms on the molecules assayed. Another experiment was conducted with the MA product to obtain information about the acute oral toxicity class methods. The tested compound was classified in the 3th toxicity class with a fixed LD (50 cut-off value of 200 mg/kg of body weight.

  12. PEGylation of lipoplexes: The right balance between cytotoxicity and siRNA effectiveness.

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    Lechanteur, Anna; Furst, Tania; Evrard, Brigitte; Delvenne, Philippe; Hubert, Pascale; Piel, Géraldine

    2016-10-10

    The delivery of small interfering RNA (siRNA) is an attractive therapeutic approach to treat several pathologies, such as viral infections or cancers. However, the stability and the efficacy of these biotherapies are still a major obstacle to their use. Cationic liposomes (DOTAP/Chol/DOPE 1/0.75/0.5M ratio) have been complexed to siRNA (lipoplexes) in order to be administrated by the vaginal route, in the context of HPV16 induced cervical preneoplastic lesions. To overcome the constraint of the cervico-vaginal mucus, PEGylation is required to allow the diffusion of lipoplexes through it. Thereby, PEGylated lipoplexes coated with three types of polyethylene glycol (PEG) as DSPE-PEG2000, DSPE-PEG750 or C8-PEG2000-Ceramide (Ceramide-PEG2000) at different densities have been developed and characterized. PEGylated lipoplexes were successfully prepared and showed a hydrodynamic diameter around 200nm, appropriate for vaginal application. In vitro assays on HPV16 positive cell lines revealed that a positive charge of PEGylated lipoplexes allows a higher mRNA knockdown by siRNA. However, the cationic property is also associated to cytotoxicity. The addition of a high percentage of PEG prevented this toxicity but seemed also to reduce siRNA endosomal escape, probably by steric hindrance. The decreasing of PEG density of Ceramide-PEG2000 to 20% allows the release of siRNA and in consequence, biological activities, contrarily to DSPE-PEG. These results suggest that Ceramide-PEG is more appropriate for siRNA delivery compared to DSPE-PEG. In conclusion, the right balance between cytotoxicity and siRNA effectiveness has been found with the transfection of lipoplexes coated with 20% of Ceramide-PEG2000. This new nanovector could have a high potential against multiple mucosal diseases, such as human papillomavirus-induced genital lesions. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines.

    Science.gov (United States)

    Abdel-Latif, Ghada A; Al-Abd, Ahmed M; Tadros, Mariane G; Al-Abbasi, Fahad A; Khalifa, Amany E; Abdel-Naim, Ashraf B

    2015-07-09

    Herceptin is considered an essential treatment option for double negative breast cancer. Resveratrol and didox are known chemopreventive agents with potential anticancer properties. The aim of the current study is to investigate the influence of resveratrol and didox on the cytotoxicity profile of herceptin in HER-2 receptor positive and HER-2 receptor negative breast cancer cell lines (T47D and MCF-7 cell lines, respectively). The IC50's of herceptin in T47D and MCF-7 were 0.133 ± 0.005 ng/ml and 23.3795 ± 1.99 ng/ml respectively. Equitoxic combination of herceptin with resveratrol or didox in T47D significantly reduced the IC50 to 0.052 ± 0.001 and 0.0365 ± 0.001 ng/ml, respectively and similar results were obtained in MCF-7. The gene expression of BCL-xl was markedly decreased in T47D cells following treatment with herceptin/resveratrol compared to herceptin alone. Immunocytochemical staining of HER-2 receptor in T47D cells showed a significant reduction after treatment with herceptin/resveratrol combination compared to herceptin alone. On the contrary, herceptin/didox combination had no significant effect on HER-2 receptor expression. Cell cycle analysis showed an arrest at G2/M phase for both cell lines following all treatments. In conclusion, herceptin/resveratrol and herceptin/didox combinations improved the cytotoxic profile of herceptin in both T47D and MCF-7 breast cancer cell lines.

  14. Effect of surface modification on the In vitro protein adsorption and cell cytotoxicity of vinorelbine nanoparticles

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    Nandhakumar Sathyamoorthy

    2017-01-01

    Full Text Available Context: Nanocarriers possessing long-circulating abilities could take advantage of the pathophysiology of tumor vasculature to achieve spatial placement. To attain such qualities, the drug carriers should possess suitable physicochemical properties such as size and surface hydrophilicity. Aim: The aim of this study was to prepare poly(ε-caprolactone nanoparticles (NPs loaded with vinorelbine bitartrate (VB and to modify its steric properties using polyethylene glycol and poloxamer. Furthermore, the influence of surface modification of NPs on their physicochemical and cell interactive properties was evaluated. Materials and Methods: NPs were prepared by double emulsion solvent extraction–evaporation technique. The prepared NPs were evaluated for their physicochemical properties, in vitro protein adsorption and cell cytotoxicity. Results and Discussion: The NPs were <250 nm with an entrapment efficiency ranging between 40% and 52%. The zeta potential of the NPs varied from −7.52 mV to −1.27 mV depending on the surface modification. The in vitro release studies exhibited a biphasic pattern with an initial burst release followed by controlled release of the drug over 72 h. The protein adsorption studies revealed that the ability to resist protein adsorption was influenced by the concentration of surface-modifying agents and the amount of proteins available for interaction. The surface-modified NPs produced cell cytotoxicity comparable to free VB at higher concentrations owing to sustained release of the drug into the cellular environment. Conclusion: The results emphasize that surface modification of nanocarriers is an essential and effective tool to dodge opsonization and phagocytosis in the physiological milieu.

  15. Overexpression of human HMW FGF-2 but not LMW FGF-2 reduces the cytotoxic effect of lentiviral gene transfer in human corneal endothelial cells.

    Science.gov (United States)

    Valtink, Monika; Knels, Lilla; Stanke, Nicole; Engelmann, Katrin; Funk, Richard H W; Lindemann, Dirk

    2012-05-31

    Recently, insertion of immuno-modulatory or anti-apoptotic genes into corneal endothelial cells (HCECs) came into focus. Basic FGF-2 occurs in one secreted (low molecular weight, LMW, 18 kD) and four nuclear (high molecular weight, HMW, 22-34 kD) isoforms. HMW isoforms are known differentiation and survival factors, while LMW FGF-2 is a known mitogen. The effect of FGF-2 overexpression of each of the five known isoforms on HCEC cell survival after lentiviral gene transfer in different culture media was investigated. Cells were transduced with lentiviral vectors encoding for each of the five FGF-2 isoforms. Transduction efficiency and expression of individual FGF-2 isoforms was assessed by marker gene transfer and western blotting. Primary HCECs were cultured and transduced in four different media previously described for HCEC cultivation or corneal organ cultivation. Cytotoxic effect of virus infection and a possible rescue effect of FGF-2 overexpression were determined by resazurin conversion assay. Transduction with FGF-2 encoding lentiviral vectors resulted in overexpression of the respective isoform in all tested cell populations. Western blotting after total cell lysis proved nuclear localization of transgenic HMW isoforms. Overexpression of HMW FGF-2-especially 34 kD FGF-2-reduced lentiviral cytotoxicity, while overexpression of LMW FGF-2 aggravated viral cytotoxicity. Cytotoxicity of lentiviral gene transfer in corneal endothelial cells may be reduced by using bicistronic vectors that encode for the target gene and the 34-kD isoform of human FGF-2. Such cotransduction of a survival factor may increase cell survival after gene transfer, thereby improving gene therapeutic approaches.

  16. Effect of post-polymerization heat-treatments on degree of conversion, leaching residual MMA and in vitro cytotoxicity of autopolymerizing acrylic repair resin.

    Science.gov (United States)

    Bural, Canan; Aktaş, Esin; Deniz, Günnur; Ünlüçerçi, Yeşim; Kızılcan, Nilgün; Bayraktar, Gülsen

    2011-11-01

    This study evaluated the effect of post-polymerization heat-treatments on degree of conversion (DC), residual methyl methacrylate concentration (MMA(r)) and in vitro cytotoxicity of autopolymerizing acrylic repair resin. A total of 336 specimens were prepared by bench- and hydroflask-curing and subjected to post-polymerization heat-treatments: a) water immersion at 60°C for 30 min, b) microwaving at 500 W for 3 min, c) combined use of water immersion and microwaving d) no treatment (as control). Specimens were eluted in cell culture medium for 1, 2, 5 and 7 days. DC and MMA(r) in eluates were measured by FTIR spectrometry and HPLC, respectively. In vitro cytotoxicity of eluates on L-929 fibroblasts was determined by XTT assay. Data were statistically analyzed with Dunn's multiple comparison and Pearson correlation tests (p≤0.05). DC was highest (99.9%) in bench- and hydroflask-cured groups which were subjected to water immersion. At all elution periods, MMA(r) was detected in eluates of all treatment groups and were higher in bench-cured groups than hydro-flask cured groups. Cell proliferation values indicated slightly cytotoxic effect throughout 7 days; regardless of the curing method or post-polymerization treatment. The correlation between MMA(r) and cell proliferation was negative after elution of 1, 2, 5 days and was only statistically significant (pMMA. Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  17. Cytotoxic, genotoxic and apoptotic effects of naringenin-oxime relative to naringenin on normal and cancer cell lines

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    Abdurrahim Kocyigit

    2016-10-01

    Conclusions: This study showed that both NG-Ox and NG possess cytotoxic, genotoxic and apoptotic activities through the production of ROS on cells, NG-Ox being the more effective one. Therefore, derived compound of NG might be used as antiproliferative agents for the treatment of cancer.

  18. Antiviral agents in hepatitis B virus transfected cell lines: Inhibitory and cytotoxic effect related to time of treatment

    NARCIS (Netherlands)

    J. Kruining; R.A. Heijtink; S.W. Schalm (Solko)

    1995-01-01

    textabstractThe antiviral and cytotoxic effects of ara-arabinoside monophosphate, 2′,3′, dideoxy-cytidine, ganciclovir, 9-2(-phosphonylmethoxyethyl) adenine, 2′,3′-dideoxy-3′-thiacytidine and recombinant interferon-alpha were studied using two human hepatitis B virus transfected hepatoma cell lines,

  19. In-vitro comparative study of cytotoxic and thrombolytic effects of methanolic extract of Cissus pentagona and Thunbergia grandiflora (Roxb. leaves

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    Mohammad Nazmul Alam

    2015-09-01

    Full Text Available Objective: To compare cytotoxic and thrombolytic activity of crude methanolic extract of Cissus pentagona (C. pentagona and Thunbergia grandiflora Roxb. (T. grandiflora leaves. Methods: The screening of cytotoxic activity was done by using brine shrimp lethality bioassay while the thrombolytic activity was evaluated by using the in vitro clot lysis model. In brief, venous blood from five healthy volunteers was allowed to form clots which were weighed and treated with the tested plant materials to disrupt the clots. Weight of clot before and after treatment provided a percentage of clot lysis and the results with streptokinase as positive control and water as negative control were compared. Results: Moderate cytotoxicity was found for both methanol extracts, and it was compared with the standard drug vincristine sulfate in the brine shrimp bioassay. In the present study, the LC50 values of the methanol crude extract of C. pentagona as well as T. grandiflora and vincristine sulfate were 291.33, 243.37 and 12.59 μg/mL, respectively. In thrombolytic study, it was found that C. pentagona and T. grandiflora showed (24.27 ± 2.61% and (19.56 ± 2.98% of clot lysis, respectively. Among the herbs studied, C. pentagona showed very significant (P < 0.001 percentage of clot lysis than T. grandiflora, compared with reference drug streptokinase [(63.54 ± 2.61%]. Conclusions: The results of the study demonstrated that the leaf of the plants contains preliminary cytotoxic effect on brine shrimp and promising thrombolytic activity in vitro when it is tested on human blood. However, further study is needed to evaluate its potential as a thrombolytic agent.

  20. Evaluation of cytotoxic, genotoxic and CYP450 enzymatic competition effects of Tanzanian plant extracts traditionally used for treatment of fungal infections.

    Science.gov (United States)

    van den Bout-van den Beukel, Carolien J P; Hamza, Omar J M; Moshi, Mainen J; Matee, Mecky I N; Mikx, Frans; Burger, David M; Koopmans, Peter P; Verweij, Paul E; Schoonen, Willem G E J; van der Ven, André J A M

    2008-06-01

    HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions.

  1. Antiproliferative and cytotoxic effects of green coffee and yerba mate extracts, their main hydroxycinnamic acids, methylxanthine and metabolites in different human cell lines.

    Science.gov (United States)

    Amigo-Benavent, M; Wang, S; Mateos, R; Sarriá, B; Bravo, L

    2017-08-01

    This work aimed at studying the effects of green coffee bean (GCBE) and yerba mate (YME) extracts, their main phenolic components (5-caffeoylquinic acid, 5-CQA; 3,5-dicaffeoylquinic acid, 3,5-DCQA) and metabolites (ferulic acid, FA; caffeic acid, CA; dihydrocaffeic acid, DHCA; and dihydroferulic acid, DHFA) along with caffeine (CAF) on the viability and proliferation of different human cell lines. Extracts (10-1000 μg/mL) and standards (10-1000 μM) were assayed in colon (Caco-2), lung (A549), oesophageal (OE-33), urinary bladder (T24) human carcinoma cells, and a non-cancer cell line (CCD-18Co). YME significantly reduced viability of cancer cells at all assayed concentrations, the higher doses also reducing cell proliferation. GCBE effects on cell viability were more effective at 100 and 1000 μg/mL, showing modest effects on cell proliferation. The highest doses of 5-CQA and 3,5-DCQA reduced cell viability and proliferation in all cell lines, whereas FA, DHCA and DHFA had lower and variable effects. Caffeine had no effect. Dietary-attainable concentrations (0.1, 1 and 10 μg/mL) of YME were tested for cytotoxicity and reactive oxygen species generation, showing no cytotoxic effect. Low concentrations of all tested compounds were non-cytotoxic to CCD-18Co cells. YME and to a lower degree GCBE, their phenolic components and metabolites may decrease cancer cell viability and proliferation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Genotoxic and cytotoxic effects of the environmental pollutant 3-nitrobenzanthrone on bladder cancer cells.

    Science.gov (United States)

    Reshetnikova, Galina; Sidorenko, Viktoriya S; Whyard, Terry; Lukin, Mark; Waltzer, Wayne; Takamura-Enye, Takeji; Romanov, Victor

    2016-11-15

    3-Nitrobenzanthrone (3-NBA), a potential human carcinogen, is present in diesel exhaust. The main metabolite of 3-NBA, 3-aminobenzanthrone, was detected in urine of miners occupationally exposed to diesel emissions. Environmental and occupational factors play an important role in development of bladder cancer (BC), one of the most frequent malignancies. It is expected that exposure of urothelium to 3-NBA and its metabolites may induce BC initiation and/or progression. To test this hypothesis, we studied geno- and cytotoxicity of 3-NBA using an in vitro BC model. 3-NBA induced higher levels of DNA adducts, reactive oxygen species and DNA breaks in aggressive T24 cells than in more differentiated RT4 cells. To understand the nature of this difference we examined the role of several enzymes that were identified as 3-NBA bio activators. However, the difference in DNA adduct formation cannot be directly linked to the different activity of any of the examined enzymes. Conversely, the difference of tested cell lines in p53 status can partly explain the distinct levels of 3-NBA-DNA adducts and DNA damage induced by 3-NBA. Therefore, we assume that more aggressive T24 cells are more predisposed for DNA adduct formation, DNA damage and, possibly, mutations and as a result further tumorigenesis. Copyright © 2016. Published by Elsevier Inc.

  3. Cytotoxic effects of TBBPA and its interactions with signalling pathways in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Strack, S.; Sander, M.; Detzel, T.; Krug, H.F. [Forschungszentrum Kalsruhe (Germany). Inst. fuer Toxikologie und Genetik; Kuch, B. [Stuttgart Univ. (Germany). Inst. fuer Siedlungswasserbau und Wasserguetewirtschaft

    2004-09-15

    Toxic effects of TBBPA published so far have been recently reviewed by Birnbaum and Staskal The LC{sub 50} indicating the acute toxicity in vivo due to a single oral dose in mice and rats were higher than 4 to 5 g/kg, however, systematically long-term in vivo studies are missing. Weak estrogenic effects have been described by Meerts et al., demonstrating for TBBPA less pronounced activity than for other brominated bisphenols. The same group described competitive interactions in vitro with human transthyretin (TTR). In binding affinity assays they could demonstrate that TBBPA binds to TTR ten times more effectively than T{sub 4}. However, the available toxicological data are still extremely limited. For a comprehensive risk assessment valid data are insufficient. The aim of this study was to evaluate possible cytotoxic effects, and to gain insights into the underlying molecular mechanisms respectively the corresponding cellular signalling processes. This approach would allow to identify sensitive end-points of cellular toxicological responses. For these molecular toxicological investigations established cell lines should be used, in order to have a suitable model for appropriate toxicological studies.

  4. Cytotoxic Effects of Salvinorin A, A Major Constituent of Salvia divinorum.

    Science.gov (United States)

    Martinho, Ana; Silva, Sara M; Gallardo, Eugenia

    2016-01-01

    S. divinorum is a psychoactive plant that has been consumed as a recreational drug of abuse in the last years. Salvinorin A is its main constituent, and is responsible for the observed psychoactive effects. Both S. divinorum and salvinorin A have become controlled drugs in several countries, but they are not listed in the Schedules of the United Nations Drug Conventions. Regarding the effects of S. divinorum consumption, almost all studies are based on in vivo or on surveys, and there are no studies in vitro on its toxicity. Furthermore, all studies are focused on the acute toxicological effects of the plant. So, it is of utmost importance to further investigate the effects of S. divinorum and salvinorin A, particularly using in vitro models, after prolonged exposures. In this context, the present work evaluated the in vitro toxicity induced by S. divinorum or salvinorin A in six cell lines, through MTT assays and LC50 determination. Overall, results showed that both S. divinorum and salvinorin A are cytotoxic, dose- and time-dependent. Also, Hep G2 and Caco 2 (to a lesser extent) cells showed lower sensitivity to S. divinorum and salvinorin A when compared to the other studied cell lines. To our knowledge, this is the first work focused on the in vitro toxicity of S. divinorum and salvinorin A using a variety of cell lines, which are extensively described in literature and have been widely used in several in vitro studies.

  5. Cytotoxic effects of sodium dodecyl benzene sulfonate on human keratinocytes are not associated with proinflammatory cytokines expression.

    Science.gov (United States)

    Mu, Zhanglei; Liu, Xiaojing; Zhao, Yan; Zhang, Jianzhong

    2014-01-01

    Keratinocytes play a crucial role in the biological function of skin barrier. The relationship between sodium lauryl sulfate (SLS) and keratinocytes has been studied. However, the cytotoxicity and effects of sodium dodecyl benzene sulfonate (SDBS), a common detergent similar to SLS, on keratinocytes are still not known. This study aimed to investigate the effects of SDBS on cytotoxicity and expression of proinflammatory cytokines in cultured human keratinocytes. This study was carried out using the keratinocytes cell line, HaCaT cells. The cytotoxicity of SDBS on HaCaT cells was evaluated with cell counting kit-8 (CCK-8) and phase-contrast microscopy. After exposure to different concentrations of SDBS, the total RNA of the HaCaT cells was extracted for evaluating the relative mRNA expression of IL-1α, IL-6, IL-8, and TNF-α by qPCR. The supernatants of cells were collected for measuring the levels of IL-6 and IL-8 by enzyme-linked immunosorbent assay (ELISA). SDBS at concentrations of 20 µg/ml and over showed direct cytotoxicity and induced morphological changes of the HaCaT cells. The mRNA expressions of IL-1α, IL-6, IL-8, and TNF-a in different concentrations of SDBS at different time were comparable with that of controls. SDBS at concentrations of 5, 10, and 15 µg/ml had no significant effects on IL-6 and IL-8 excretion from HaCaT cells after 24-hour exposure. Moreover, no significant effects on the IL-6 and IL-8 excretion were found after 10 and 15 µg/ml SDBS stimulations for 6, 12, and 24 hours, respectively. SDBS at higher concentrations had cytotoxicity on HaCaT cells but had no effects on the mRNA expression of IL-1α, IL-6, IL-8, and TNF-a, that was different from SLS.

  6. Cytotoxic and apoptotic effects of six herbal plants against the human hepatocarcinoma (HepG2 cell line

    Directory of Open Access Journals (Sweden)

    Nonpunya Apiyada

    2011-10-01

    Full Text Available Abstract Background Six plants from Thailand were evaluated for their cytotoxicity and apoptosis induction in human hepatocarcinoma (HepG2 as compared to normal African green monkey kidney epithelial cell lines. Methods Ethanol-water crude extracts of the six plants were tested with neutral red assay for their cytotoxicity after 24 hours of exposure to the cells. Apoptotic induction was tested in the HepG2 cells with diamidino-2-phenylindole staining. DNA fragmentation, indicative of apoptosis, was analyzed with agarose gel electrophoresis. Alkylation, indicative of DNA damage, was also evaluated in vitro by 4-(4'-nitrobenzyl pyridine assay. Results The extract of Pinus kesiya showed the highest selectivity (selectivity index = 9.6 and potent cytotoxicity in the HepG2 cell line, with an IC50 value of 52.0 ± 5.8 μg/ml (mean ± standard deviation. Extract of Catimbium speciosum exerted cytotoxicity with an IC50 value of 55.7 ± 8.1 μg/ml. Crude extracts from Glochidion daltonii, Cladogynos orientalis, Acorus tatarinowii and Amomum villosum exhibited cytotoxicity with IC50 values ranging 100-500 μg/ml. All crude extracts showed different alkylating abilities in vitro. Extracts of P. kesiya, C. speciosum and C. orientalis caused nuclei morphological changes and DNA laddering. Conclusion The extracts of C. speciosum, C. orientalis and P. kesiya induced apoptosis. Among the three plants, P. kesiya possessed the most robust anticancer activity, with specific selectivity against HepG2 cells.

  7. Evaluation of cytotoxic effects of Anbarnesa on fibroblast L929: Can it be used as a mouthwash?

    Directory of Open Access Journals (Sweden)

    Hassan Ali Shafiee

    2014-01-01

    Full Text Available Aims: In Iranian traditional medicine Anbarnesa (derived from smoke from burning female donkey′s stool has been used to treat ulcers and inflammatory conditions like stomatitis and ear infections (otitis. We assess the properties of Anbarnesa as an alternative mouthwash. Materials and Methods: In this experimental study, Anbarnesa smoke was analyzed using aGC-mass device. The smoke collected was dissolved at different densities in propylene glycol and incubated in Dulbecco′s modified Eagle′s medium in direct contact with fibroblast cells. Assessment of cytotoxicity was done at 1, 24 and 72 h. Cell viability was measured by methyl thiazolyl tetrazolium test, and ELISA Reader machine was used to read the results. Data were analyzed using one-way ANOVA test. Results: The findings of this study showed Anbarnesa was nontoxic in 1/64, 1/128 and 1/256 dilutions. In 1/32 dilution, toxicity was seen after 72 h. In dilutions, 1/8 and 1/16 toxicity were seen in the 1 st h. Conclusion: According to the initial results of Anbarnesa may be used as an alternative mouthwash with fewer side-effects for plaque control and prevention of periodontal disease.

  8. Cytotoxic Effects of Vicicitus globosus (Class Dictyochophyceae and Chattonella marina (Class Raphidophyceae on Rotifers and Other Microalgae

    Directory of Open Access Journals (Sweden)

    Fook Hoe Chang

    2015-06-01

    Full Text Available Cultures of Vicicitus globosus (previously Chattonella globosa and Chattonella marina, established during the 2010 fish kill event in Mahanga Bay, Wellington Harbour, are confirmed to be cytotoxic. The aggregate potency of lipophilic cell extracts of each species were evaluated using three species each of flagellates, dinoflagellates and diatoms, and a rotifer as test organisms. The cell extract of V. globosus destroyed cells of all nine microalgae in a matter of a few minutes to less than 15 min, while that of C. marina, destroyed all species over 10 to 30 min. The lipophilic extract of V. globosus caused partial disintegration of both theca wall and cytoplasm of cells of Alexandrium catenella in a matter of minutes. This effect, however, was not observed in cells of A. catenella exposed to that of C. marina. Tests conducted on rotifers showed similar fast-acting trends, with animals exposed to a cell extract of V. globosus died in a much shorter time (Lt50 = 80 min than those exposed to that of C. marina (20 h.

  9. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: Screening cytotoxicity and genotoxicity endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Esperanza, Marta; Cid, Ángeles; Herrero, Concepción; Rioboo, Carmen, E-mail: carmen.rioboo@udc.es

    2015-08-15

    Highlights: • Mitochondrial membrane potential constituted the most sensitive parameter assayed. • Several genotoxicity methods were applied for first time in ecotoxicological studies. • Oxidative DNA base damage (8-OHdG) was induced by paraquat exposure. • Cells with DNA strand breakage and subG1-nuclei increased in treated cultures. • Typical apoptosis hallmarks were observed in microalgal cells exposed to paraquat. - Abstract: Since recent evidence has demonstrated that many types of chemicals exhibit oxidative and/or genotoxic potential on living organisms, reactive oxygen species (ROS) formation and DNA damage are currently the best accepted paradigms to assess the potential hazardous biological effects of a wide range of contaminants. The goal of this study was to evaluate the sensitivity of different cytotoxicity and genotoxicity responses on the model microalga Chlamydomonas reinhardtii exposed to the prooxidant herbicide paraquat. In addition to the growth endpoint, cell viability, mitochondrial membrane potential and presence of reactive oxygen species (ROS) were assayed as potential markers of cytotoxicity using flow cytometry (FCM). To study the effects of paraquat on C. reinhardtii DNA, several genotoxicity approaches were implemented for the first time in an ecotoxicological study on microalgae. Oxidative DNA base damage was analysed by measuring the oxidative DNA lesion 8-OHdG by FCM. DNA fragmentation was analysed by different methods: comet assay, and cell cycle analysis by FCM, with a particular focus on the presence of subG1-nuclei. Finally, effects on morphology of nuclei were monitored through DAPI staining. The evaluation of these endpoints showed that several physiological and biochemical parameters reacted to oxidative stress disturbances with greater sensitivity than integrative parameters such as growth rates or cell viability. The experiments revealed concentration-dependent cytotoxicity (ROS formation, depolarization of

  10. Biomonitoring genotoxicity and cytotoxicity of Microcystis aeruginosa (Chroococcales, cyanobacteria) using the Allium cepa test.

    Science.gov (United States)

    Laughinghouse, Haywood Dail; Prá, Daniel; Silva-Stenico, Maria Estela; Rieger, Alexandre; Frescura, Viviane Dal-Souto; Fiore, Marli Fátima; Tedesco, Solange Bosio

    2012-08-15

    Water pollution caused by toxic cyanobacteria is a problem worldwide, increasing with eutrophication. Due to its biological significance, genotoxicity should be a focus for biomonitoring pollution owing to the increasing complexity of the toxicological environment in which organisms are exposed. Cyanobacteria produce a large number of bioactive compounds, most of which lack toxicological data. Microcystins comprise a class of potent cyclic heptapeptide toxins produced mainly by Microcystis aeruginosa. Other natural products can also be synthesized by cyanobacteria, such as the protease inhibitor, aeruginosin. The hepatotoxicity of microcystins has been well documented, but information on the genotoxic effects of aeruginosins is relatively scarce. In this study, the genotoxicity and ecotoxicity of methanolic extracts from two strains of M. aeruginosa NPLJ-4, containing high levels of microcystin, and M. aeruginosa NPCD-1, with high levels of aeruginosin, were evaluated. Four endpoints, using plant assays in Allium cepa were applied: rootlet growth inhibition, chromosomal aberrations, mitotic divisions, and micronucleus assays. The microcystin content of M. aeruginosa NPLJ-4 was confirmed through ELISA, while M. aeruginosa NPCD-1 did not produce microcystins. The extracts of M. aeruginosa NPLJ-4 were diluted at 0.01, 0.1, 1 and 10 ppb of microcystins; the same procedure was used to dilute M. aeruginosa NPCD-1 used as a parameter for comparison, and water was used as the control. The results demonstrated that both strains inhibited root growth and induced rootlet abnormalities. The strain rich in aeruginosin was more genotoxic, altering the cell cycle, while microcystins were more mitogenic. These findings indicate the need for future research on non-microcystin producing cyanobacterial strains. Understanding the genotoxicity of M. aeruginosa extracts can help determine a possible link between contamination by aquatic cyanobacteria and high risk of primary liver

  11. Antiproliferative and cytotoxic effects of purple pitanga (Eugenia uniflora L.) extract on activated hepatic stellate cells.

    Science.gov (United States)

    Denardin, Cristiane C; Parisi, Mariana M; Martins, Leo A M; Terra, Silvia R; Borojevic, Radovan; Vizzotto, Márcia; Perry, Marcos L S; Emanuelli, Tatiana; Guma, Fátima T C R

    2014-01-01

    The presence of phenolic compounds in fruit- and vegetable-rich diets has attracted researchers' attention due to their health-promoting effects. The objective of this study was to evaluate the effects of purple pitanga (Eugenia uniflora L.) extract on cell proliferation, viability, mitochondrial membrane potential, cell death and cell cycle in murine activated hepatic stellate cells (GRX). Cell viability by 3-(4,5-dimethylthiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was significantly decreased on cells treated with 50 and 100 µg ml(-1) of purple pitanga extract for 48 and 72 h, and the percentage of dead cell stained with 7-amino-actinomycin D was significantly higher in treated cells. The reduction of cell proliferation was dose dependent, and we also observed alterations on cell cycle progression. At all times studied, GRX cells treated with 50 and 100 µg ml(-1) of purple pitanga showed a significant reduction in cellular mitochondrial content as well as a decrease in mitochondrial membrane potential. Furthermore, our results indicated that purple pitanga extract induces early and late apoptosis/necrosis and necrotic death in GRX cells. This is the first report describing the antiproliferative, cytotoxic and apoptotic activity for E. uniflora fruits in hepatic stellate cells. The present study provides a foundation for the prevention and treatment of liver fibrosis, and more studies will be carried to elucidate this effect. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Differential effects of radical scavengers on X-ray-induced mutation and cytotoxicity in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Corn, B.W.; Liber, H.L.; Little, J.B.

    1987-01-01

    The cytotoxic and mutagenic effects of X irradiation on a human lymphoblast cell line were examined in the presence of two radioprotective agents which modulate damage to DNA. The cells were treated with X rays alone or in the presence of either dimethyl sulfoxide or cysteamine. Surviving fraction and mutation to trifluorothymidine resistance (tk locus) and to 6-thioguanine resistance (hgprt locus) were measured. Survival was enhanced when the cells were irradiated in the presence of dimethyl sulfoxide; the D0 rose from 58 to 107 rad. However, at both genetic loci the induced mutant fractions were identical in the presence or absence of dimethyl sulfoxide. Survival was enhanced to a greater degree when the cells were irradiated in the presence of cysteamine; the D0 rose from 58 to 200 rad. Cysteamine also protected the cells from X-ray-induced mutation; the frequencies of X-ray-induced mutation at both the tk and hgprt loci were reduced by 50-75%. No protective effects were observed unless dimethyl sulfoxide or cysteamine was present during irradiation. These findings are discussed in terms of the hypothesis that, unlike for cell killing, radiation-induced mutagenesis in human lymphoblast cells is not mediated by the actions of aqueous free radicals, but rather by the direct effects of ionizing radiation.

  13. Cytotoxic, genotoxic/antigenotoxic and mutagenic/antimutagenic effects of the venom of the wasp Polybia paulista.

    Science.gov (United States)

    Hoshina, Márcia M; Santos, Lucilene D; Palma, Mario S; Marin-Morales, Maria A

    2013-09-01

    Hymenoptera venoms are constituted by a complex mixture of chemically or pharmacologically bioactive agents, such as phospholipases, hyaluronidases and mastoparans. Venoms can also contain substances that are able to inhibit and/or diminish the genotoxic or mutagenic action of other compounds that are capable of promoting damages in the genetic material. Thus, the present study aimed to assess the effect of the venom of Polybia paulista, a neotropical wasp, by assays with HepG2 cells maintained in culture. The cytotoxic potential of the wasp venom, assessed by the methyl thiazolyl tetrazolium assay (MTT assay), was tested for the concentrations of 10 μg/mL, 5 μg/mL and 1 μg/mL. As these concentrations were not cytotoxic, they were used to evaluate the genotoxic (comet assay) and mutagenic potential (micronucleus test) of the venom. In this study, it was verified that these concentrations induced damages in the DNA of the exposed cells, and it was necessary to test lower concentrations until it was found those that were not considered genotoxic and mutagenic. The concentrations of 1 ng/mL, 100 pg/mL and 10 pg/mL, which did not induce genotoxicity and mutagenicity, were used in four different treatments (post-treatment, pre-treatment, simultaneous treatment with and without incubation), in order to evaluate if these concentrations were able to inhibit or decrease the genotoxic and mutagenic action of methyl methanesulfonate (MMS). None of the concentrations was able to inhibit and/or decrease the MMS activity. The genotoxic and mutagenic activity of the venom of P. paulista could be caused by the action of phospholipase, mastoparan and hyaluronidase, which are able to disrupt the cell membrane and thereby interact with the genetic material of the cells or even facilitate the entrance of other compounds of the venom that can act on the DNA. Another possible explanation for the genotoxicity and mutagenicity of the venom can be the presence of substances able

  14. Cytotoxic (A549) and antimicrobial effects of Methylobacterium sp. isolate (ERI-135) from Nilgiris forest soil, India.

    Science.gov (United States)

    Balachandran, C; Duraipandiyan, V; Ignacimuthu, S

    2012-09-01

    To assess the antimicrobial and cytotoxic effects of Methylobacterium sp. isolated from soil sample of Doddabetta forest, Nilgiris, Western Ghats of Tamil Nadu. Isolation of Methylobacterium was performed from soils by serial dilution plate technique. The strain was grown in modified nutrient gulucose agar (MNGA) medium to study the morphology and biochemical characteristics. Methylobacterium sp. was screened for its antimicrobial activity against pathogenic bacteria and fungi. The strain was subjected to 16S rRNA analysis and was identified as Methylobacterium sp. The nucleotide sequence of the 16S rRNA gene of the isolate exhibited close similarity with other Methylobacterium sp. and has been submitted to Genbank. The antibacterial substances were extracted using chloroform and ethyl acetate from MNGA medium in which ERI-135 had grown for 5 d at 30 °C. Cytotoxic effect was also studied. GC-MS analysis was carried out. The antimicrobial activity was assessed using broth micro dilution technique. Ethyl acetate extract showed activity against bacteria such as Bacillus subtilis, Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa, Salmonella typhimurium, Shigella flexneri, Enterobacter aerogenes, Staphylococcus aureu and Staphylococcus epidermidis (S. epidermidis) and fungi such as, Candida albicans and Trichophyton rubrum. The lowest minimum inhibitory concentrations were: 250 µg/mL against S. epidermidis and 250µg/mL against K. pneumonia. The isolate had the ability to produce enzymes such as protease. The exyract showed cytotoxic effect in human adenocarcinoma cancer cell line (A549). GC-MS analysis showed the presence of isovaleric acid (3.64%), 2-Methylbutanoic acid (5.03%), isobutyramide (5.05%), N,N-oimethylformamide-di-t-butylacetal (9.79%), benzeneacetamide (15.56%), octyl butyl phthalate (3.59%) and diisooctyl phthalate (5.79) in the extract. Methylobacterium sp. (ERI-135) showed promising antibacterial and cytotoxic activity. This is the first

  15. Effect of metformin and celecoxib on cytotoxicity and release of GDF-15 from human mesenchymal stem cells in high glucose condition.

    Science.gov (United States)

    Zafarvahedian, Elaheh; Roohi, Azam; Sepand, Mohammad Reza; Ostad, Seyed Nasser; Ghahremani, Mohammad Hossein

    2017-10-01

    Mesenchymal stem cells (MSCs) have therapeutic potential for treatment of diabetes. However, in vitro behavior of MSCs in high glucose condition as well as presence of glucose lowering agents is not fully understood. Because MSCs have an important role in tissue repair, we examined the effects of metformin and celecoxib on viability of MSCs in different glucose conditions. MSCs, from umbilical cord blood, were cultured in normoglycemic (glucose 5.5 mM), midglycemic (glucose 10 mM), and hyperglycemic (glucose 25 mM) conditions, and the cell viability was evaluated by MTT assay. The cytotoxicity and secretion of GDF-15 were further tested in MSCs treated with metformin and celecoxib in various glucose concentrations. Our results showed that high glucose condition lowered viability of MSCs. Metformin treatment also inhibited proliferation of MSCs, but its toxicity was not changed in high glucose condition. Celecoxib induced cytotoxicity in MSCs, and the toxicity was increased in high glucose condition. Metformin and celecoxib induced release from MSCs; however, high glucose inhibited the metformin-induced GDF-15 release. These findings suggested that metformin did not increase the cytotoxicity of high glucose condition in MSCs. Moreover, celecoxib treatment in diabetic condition can reduce the viability of MSCs to proliferate and regenerate perhaps via change in release of GDF-15. Copyright © 2017 John Wiley & Sons, Ltd.

  16. In vitro antifungal activity and cytotoxic effect of essential oils and extracts of medicinal and aromatic plants against Candida krusei and Aspergillus fumigatus

    Directory of Open Access Journals (Sweden)

    Julieth Correa-Royero

    2010-09-01

    Full Text Available The plants are usually used in traditional medicine as antimicrobial agents and their essential oils and extracts have been known to possess antifungal activity. The aim of this study was to evaluate in vitro the activity of 32 essential oils and 29 extracts against C. krusei and A. fumigatus as well as the cytotoxic effect on Vero cells. Time-kill curve and interaction between antifungals and the most active sample against C. krusei, was also evaluated. The oils from C. ambrosioides and the extract of M. cucullata showed antifungal activity against C. krusei (GM-MIC 7.82 and 31.25 µg/mL, respectively. L. citriodora was actives against C. krusei and A. fumigates (GM-MIC = 99.21 µg/mL and 62.5 µg/mL respectively. Time-kill assays done with C. ambrosioides oil showed fungicidal activity at 4x MIC. The interaction of C. ambrosioides oil with itraconazole and amphotericin B was tested following the chequerboard technique. No interaction was detected for the combination of C. ambrosioides oil with amphotericin B and itraconazole (FICI range = 1.03-1.06 and 1.03-1.00, respectively. Cytotoxicity assays for all samples were carried out with MTT. Only the oil from Hedyosmun sp. and L. dulcis were cytotoxic.

  17. Effects of Simulated Human Gastrointestinal Digestion of Two Purple-Fleshed Potato Cultivars on Anthocyanin Composition and Cytotoxicity in Colonic Cancer and Non-Tumorigenic Cells.

    Science.gov (United States)

    Kubow, Stan; Iskandar, Michèle M; Melgar-Bermudez, Emiliano; Sleno, Lekha; Sabally, Kebba; Azadi, Behnam; How, Emily; Prakash, Satya; Burgos, Gabriela; Felde, Thomas Zum

    2017-08-29

    A dynamic human gastrointestinal (GI) model was used to digest cooked tubers from purple-fleshed Amachi and Leona potato cultivars to study anthocyanin biotransformation in the stomach, small intestine and colonic vessels. Colonic Caco-2 cancer cells and non-tumorigenic colonic CCD-112CoN cells were tested for cytotoxicity and cell viability after 24 h exposure to colonic fecal water (FW) digests (0%, 10%, 25%, 75% and 100% FW in culture media). After 24 h digestion, liquid chromatography-mass spectrometry identified 36 and 15 anthocyanin species throughout the GI vessels for Amachi and Leona, respectively. The total anthocyanin concentration was over thirty-fold higher in Amachi compared to Leona digests but seven-fold higher anthocyanin concentrations were noted for Leona versus Amachi in descending colon digests. Leona FW showed greater potency to induce cytotoxicity and decrease viability of Caco-2 cells than observed with FW from Amachi. Amachi FW at 100% caused cytotoxicity in non-tumorigenic cells while FW from Leona showed no effect. The present findings indicate major variations in the pattern of anthocyanin breakdown and release during digestion of purple-fleshed cultivars. The differing microbial anthocyanin metabolite profiles in colonic vessels between cultivars could play a significant role in the impact of FW toxicity on tumor and non-tumorigenic cells.

  18. PEG-PE/clay composite carriers for doxorubicin: Effect of composite structure on release, cell interaction and cytotoxicity.

    Science.gov (United States)

    Kohay, Hagay; Sarisozen, Can; Sawant, Rupa; Jhaveri, Aditi; Torchilin, Vladimir P; Mishael, Yael G

    2017-06-01

    A novel drug delivery system for doxorubicin (DOX), based on organic-inorganic composites was developed. DOX was incorporated in micelles (M-DOX) of polyethylene glycol-phosphatidylethanolamine (PEG-PE) which in turn were adsorbed by the clay, montmorillonite (MMT). The nano-structures of the PEG-PE/MMT composites of LOW and HIGH polymer loadings were characterized by XRD, TGA, FTIR, size (DLS) and zeta measurements. These measurements suggest that for the LOW composite a single layer of polymer intercalates in the clay platelets and the polymer only partially covers the external surface, while for the HIGH composite two layers of polymer intercalate and a bilayer may form on the external surface. These nanostructures have a direct effect on formulation stability and on the rate of DOX release. The release rate was reversely correlated with the degree of DOX interaction with the clay and followed the sequence: M-DOX>HIGH formulation>LOW formulation>DOX/MMT. Despite the slower release from the HIGH formulation, its cytotoxicity effect on sensitive cells was as high as the "free" DOX. Surprisingly, the LOW formulation, with the slowest release, demonstrated the highest cytotoxicity in the case of Adriamycin (ADR) resistant cells. Confocal microscopy images and association tests provided an insight into the contribution of formulation-cell interactions vs. the contribution of DOX release rate. Internalization of the formulations was suggested as a mechanism that increases DOX efficiency, particularly in the ADR resistant cell line. The employment of organic-inorganic hybrid materials as drug delivery systems, has not reached its full potential, however, its functionality as an efficient tunable release system was demonstrated. DOX PEG-PE/clay formulations were design as an efficient drug delivery system. The main aim was to develop PEG-PE/clay formulations of different structures based on various PEG-PE/clay ratios in order to achieve tunable release rates, to control

  19. Analyzing cytotoxic effects of selected isothiazol-3-one biocides using the toxic ratio concept and structure-activity relationship considerations.

    Science.gov (United States)

    Arning, Jürgen; Matzke, Marianne; Stolte, Stefan; Nehen, Frauke; Bottin-Weber, Ulrike; Böschen, Andrea; Abdulkarim, Salha; Jastorff, Bernd; Ranke, Johannes

    2009-12-01

    To demonstrate how baseline toxicity can be separated from other more specific modes of toxic action and to address possible pitfals when dealing with hydrophobic substances, the four isothiazol-3-one biocides N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT), and 4,5-dichloro-N-octylisothiazol-3-one (DCOIT) as an example for reactive electrophilic xenobiotics were tested for their cytotoxic effects on the human hepatoblastoma cell line Hep G2, on the marine bacterium Vibrio fischeri, and on the limnic green alga Scenedesmus vacuolatus. In each of the three test systems, toxic effects were observed in a consistent pattern. The two chlorinated compounds and OIT were found to be significantly more toxic than MIT. As compared to baseline toxicants, the small and polar MIT and CIT exhibited pronounced excess toxicity in each of the three test systems that is presumably triggered by their intrinsic reactivity toward cellular thiols. In contrast, OIT and DCOIT showed mainly toxicities that could be explained by their hydrophobicity. Analyzing and comparing these results using the toxic ratio concept and with data that indicate a dramatic depletion of cellular glutathione levels after incubation with DCOIT reveals that for highly hydrophobic substances, baseline level toxicity in an assay for acute toxicity can lead to an oversight of other more specific modes of toxic action that may cause significant effects that might be less reversible than those caused by unreactive baseline toxicants. This possibility should be taken into account in the hazard assessment of chemicals that are both hydrophobic and reactive.

  20. Effect of resin chemistry on depth of cure and cytotoxicity of dental resin composites

    Energy Technology Data Exchange (ETDEWEB)

    Susila Anand, V. [Rehabilitation Bioengineering Group, Department of Engineering Design, Indian Institute of Technology Madras, Chennai 600036 (India); Department of Conservative Dentistry and Endodontics, Saveetha Dental College, Saveetha University, Chennai 600077 (India); Balasubramanian, Venkatesh, E-mail: chanakya@iitm.ac.in [Rehabilitation Bioengineering Group, Department of Engineering Design, Indian Institute of Technology Madras, Chennai 600036 (India)

    2014-02-15

    Highlights: • Dental composites have differences in polymerization within 2 mm thickness. • Degree of conversion alone may not affect the biocompatibility of composite. • Unreacted double bonds in dental composites may influence biocompatibility. • Magnitude of double bonds depends on the polymerization and chemical composition. • These influence biocompatibility especially if they possess lipophylic properties. -- Abstract: New dental composite restorative materials are being introduced aiming to overcome the disadvantages of contemporary materials. Hence there is a need to analyze the critical properties of these composites to aid in clinical application. This study aims to comparatively analyze the degree of conversion (DC), residual reactivity (DBC/reactivity) and cytotoxicity of 2 composites based on different resin chemistry. Ceram X and Filtek P90 were used in the study to prepare disc shaped samples of 2 mm thickness and 4 mm diameter. The samples for cytotoxicity were cured for 40 s and those of Fourier Transform Infra-red Spectroscopy (FTIR) (DBC/reactivity and DC) for 5 s, 10 s, 20 s and 40 s, at an average intensity of 800 mW/cm{sup 2} with Quartz–Tungsten–Halogen (QTH) light. DC was calculated in 60–100 μm thick and 6 mm diameter samples. Double bonds concentration/reactivity was measured in approximately 80 μm thick sections prepared from the 2 mm thick discs using a hard tissue microtome. The cell viability was scored by Trypan blue exclusion staining technique at 24 h and 48 h. Both composites showed a progressive increase in double bonds/reactivity as the distance from curing probe increased which was inversely proportional to the curing time. The DC of Filtek P90 was 20% and 96% and that of Ceram X 33% and 50% at 5 s and 40 s, respectively. Ceram X showed statistically significantly higher cell viability score at both 24 h and 48 h than Filtek P90. The results were statistically analyzed using non-parametric Kruskal

  1. Cytotoxic effects of the Viscum album L. extract on Ehrlich tumour cells in vivo.

    Science.gov (United States)

    Cebović, Tatyana; Spasić, Slavica; Popović, Mira

    2008-08-01

    To date most pharmacological studies on mistletoe (Viscum album L.) have focused on the therapeutic properties of its polar extracts. This study examined the non-polar constituents of Viscum album and their biological activities. Supercritical CO(2) extraction coupled with gas chromatography/mass spectrometry (GC/MS) was used to selectively extract and identify compounds in Viscum album leaves. Several non-polar classes of compounds were identified in the extract. In addition, a volatile fraction was identified that contained several novel terpene molecules. The hypothesis was tested that the Viscum album extract exhibits cytotoxic properties in Ehrlich carcinoma (EAC) cells in vivo due to the induction of oxidative stress. A significant reduction in the incidence of cancer was observed in all groups that received the Viscum album extract compared with the EAC control group. The largest decrease was observed in mice pretreated with the Viscum album extract, although significantly reduced numbers of EAC cells were also observed in animals with developed carcinoma. The activities of antioxidative enzymes in the EAC cells suggested the absence of oxidative stress. However, changes in the antioxidative enzymes activities observed after administration of the Viscum album extract might be due to the induction of oxidative stress in the EAC cells.

  2. Cytotoxic effects of betaxolol on healthy corneal endothelial cells both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Ying Miao

    2014-02-01

    Full Text Available AIM: To demonstrate the cytotoxic effect of betaxolol and its underlying mechanism on human corneal endothelial cells(HCE cells in vitro and cat corneal endothelial cells(CCE cells in vivo, providing experimental basis for safety anti-glaucoma drug usage in clinic of ophthalmology.METHODS: In vivo and in vitro experiments were conducted to explore whether and how betaxolol participates in corneal endothelial cell injury. The in vitro morphology, growth status, plasma membrane permeability, DNA fragmentation, and ultrastructure of HCE cells treated with 0.021875-0.28g/L betaxolol were examined by light microscope, 3-(4,5-dimethylthiahiazo (-z-y1-3,5-di-phenytetrazoliumromide (MTT assay, acridine orange (AO/ethidium bromide (EB double-fluorescent staining, DNA agarose gel electrophoresis, and transmission electron microscope (TEM. The in vivo density, morphology, and ultrastructure of CCE cells, corneal thickness, and eye pressure of cat eyes treated with 0.28g/L betaxolol were investigated by specular microscopy, applanation tonometer, alizarin red staining, scanning electron microscope (SEM, and TEM.RESULTS: Exposure to betaxolol at doses from 0.0875g/L to 2.8g/L induced morphological and ultrastructural changes of in vitro cultured HCE cells such as cytoplasmic vacuolation, cellular shrinkage, structural disorganization, chromatin condensation, and apoptotic body appearance. Simultaneously, betaxolol elevated plasma membrane permeability and induced DNA fragmentation of these cells in a dose-dependent manner in AO/EB staining. Furthermore, betaxolol at a dose of 2.8g/L also induced decrease of density of CCE cells in vivo, and non-hexagonal and shrunk apoptotic cells were also found in betaxolol-treated cat corneal endothelia.CONCLUSION: Betaxolol has significant cytotoxicity on HCE cells in vitro by inducing apoptosis of these cells, and induced apoptosis of CCE cells in vivo as well. The findings help provide new insight into the apoptosis

  3. Cytotoxic Effect of Iron Oxide Nanoparticles on Mouse Embryonic Stem Cells by MTT Assay

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    Homa Mohseni Kouchesfehani

    2016-07-01

    Full Text Available Background: Despite the wide range of applications, there is a serious lack of information on the impact of the nanoparticles on human health and the environment. The present study was done to determine the range of dangerous concentrations of iron oxide nanoparticle and their effects on mouse embryonic stem cells. Methods: Iron oxide nanoparticles with less than 20 nanometers diameter were encapsulated by a PEG-phospholipid. The suspension of iron oxide nanoparticles was prepared using the culture media and cell viability was determined by MTT assay. Results: MTT assay was used to examine the cytotoxicity of iron oxide nanoparticle s. Royan B1 cells were treated with medium containing different concentrations (10, 20, 30, 40, 50, and 60µg/ml of the iron oxide nanoparticle. Cell viability was determined at 12 and 24 hours after treatment which showed significant decreases when concentration and time period increased. Conclusion: The main mechanism of nanoparticles action is still unknown, but in vivo and in vitro studies in different environments suggest that they are capable of producing reactive oxygen species (ROS. Therefore, they may have an effect on the concentration of intracellular calcium, activation of transcription factors, and changes in cytokine. The results of this study show that the higher concentration and duration of treatment of cells with iron oxide nanoparticles increase the rate of cell death.

  4. Synthesis and cytotoxic effect on RD cell line of Pd(II and Cu(II

    Directory of Open Access Journals (Sweden)

    Mahasin Alias

    2016-01-01

    Full Text Available Complexes of Cr(III, Cd(II, Ni(II, Pd(II and Cu(II with new ligand sodium [5-(p-nitro phenyl-/4-phenyl-1,2,4-triazole-3-dithiocarbamato hydrazide] (TRZ.DTC have been prepared and characterized in solid state by using flame atomic absorption, elemental analysis C.H.N.S, FT-IR, UV–vis spectrophotometry, thermal analysis TGA, conductivity and magnetic susceptibility measurements. The ratio of M:L and logK was determined by molar ratio method. From the spectral studies, an octahedral monomer structure was proposed for all complexes except copper(II which has a dimeric structure. Cadmium(II has tetrahedral geometry. Structural geometries of these compounds were also suggested in gas phase by using hyper chem-8 program. The heat of formation, binding energy, and dipole moment were calculated by PM3 and ZINDO/1 methods. ZINDO/1 was used to evaluate the vibration spectra of the (TRZ.DTC ligand and starting material as authentic compound. Cytotoxic effect of Pd, Cu and ligand was evaluated against Rhabdomyosarcoma cell line by using four different concentrations (500, 250, 125 & 62.5 μg/ml in three exposure times 24, 48 and 72 h and compared this effect with control positive Cis-Pt. The efficiency of these new compounds on RD cell line may be attributed to blocking the protein synthesis of the cells.

  5. Cytotoxic effects of sulfuric acid mist, carbon particulates, and their mixtures on hamster tracheal epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Schiff, L.J. (IIT Research Inst., Chicago, IL); Bryne, M.M.; Fenters, J.D.; Graham, J.A.; Gardner, D.E.

    1979-08-01

    Hamster tracheal tissue was used to study the effects of H/sub 2/SO/sub 4/ mist, carbon particles, and mixtures of the two on cilia beating frequency and morphological alterations of respiratory epithelium. Hamsters were exposed for 3 h to 1.1 mg/m/sup 3/ H/sub 2/SO/sub 4/ (mean size, 0.12 ..mu..m) and 1.5 mg/m/sup 3/ carbon (mean size, 0.3 ..mu..m) particle aerosols alone or in combination. Trachea of animals exposed in vivo to the mixture and held in vivo showed cytotoxic effects in the epithelium that were greater than those produced by either the acid mist or carbon alone. In tracheas of hamsters exposed in vivo and maintained in vitro the damage produced by acid mist-carbon mixture did not differ significantly from that produced by acid mist per se but was greater than that observed after exposure to carbon. Organ cultures of tracheal rings exposed for 3 h to a 1:10/sup 6/ dilution of concentrated H/sub 2/SO/sub 4/ and 100 ..mu..g/ml carbon produced epithelial damage in vitro similar to that seen in in vivo exposures. The extent of recovery over a period of 72 h was also studied following different combinations of in vivo and in vitro exposure and/or maintenance.

  6. Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats

    Directory of Open Access Journals (Sweden)

    Nadine Haberl

    2013-12-01

    Full Text Available Silver nanoparticles (AgNP are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly. To evaluate possible adverse health effects, especially to the lungs, the current study focused on the cytotoxic and proinflammatory effects of AgNP after the intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm showing little agglomeration in aqueous suspension were instilled intratracheally. After 24 hours, the lungs were lavaged, and lactate dehydrogenase (LDH, total protein, and cytokine levels as well as total and differential cell counts were measured in the bronchoalveolar lavage fluid (BALF. Instillation of 50 µg PVP-AgNP did not result in elevated LDH, total protein, or cytokine levels in BALF compared to the control, whereas instillation of 250 µg PVP-AgNP caused a significant increase in LDH (1.9-fold and total protein (1.3-fold levels as well as in neutrophil numbers (60-fold of BALF. Furthermore, while there was no change in BALF cytokine levels after the instillation of 50 µg PVP-AgNP, instillation of 250 µg PVP-AgNP resulted in significantly increased levels of seven out of eleven measured cytokines. These finding suggest that exposure to inhaled AgNP can induce moderate pulmonary toxicity, but only at rather high concentrations.

  7. Silver nanoparticles with antimicrobial activities against Streptococcus mutans and their cytotoxic effect.

    Science.gov (United States)

    Pérez-Díaz, Mario Alberto; Boegli, Laura; James, Garth; Velasquillo, Cristina; Sánchez-Sánchez, Roberto; Martínez-Martínez, Rita-Elizabeth; Martínez-Castañón, Gabriel Alejandro; Martinez-Gutierrez, Fidel

    2015-10-01

    Microbial resistance represents a challenge for the scientific community to develop new bioactive compounds. The goal of this research was to evaluate the antimicrobial activity of silver nanoparticles (AgNPs) against a clinical isolate of Streptococcus mutans, antibiofilm activity against mature S. mutans biofilms and the compatibility with human fibroblasts. The antimicrobial activity of AgNPs against the planktonic clinical isolate was size and concentration dependent, with smaller AgNPs having a lower minimum inhibitory concentration. A reduction of 2.3 log in the number of colony-forming units of S. mutans was observed when biofilms grown in a CDC reactor were exposed to 100 ppm of AgNPs of 9.5±1.1 nm. However, AgNPs at high concentrations (>10 ppm) showed a cytotoxic effect upon human dermal fibroblasts. AgNPs effectively inhibited the growth of a planktonic S. mutans clinical isolate and killed established S. mutans biofilms, which suggests that AgNPs could be used for prevention and treatment of dental caries. Further research and development are necessary to translate this technology into therapeutic and preventive strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Cardiorenal Syndrome Type 5: In Vitro Cytotoxicity Effects on Renal Tubular Cells and Inflammatory Profile

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    Alessandra Brocca

    2015-01-01

    Full Text Available Background. Cardiorenal Syndrome Type 5 (CRS Type 5 reflects concomitant cardiac and renal dysfunctions in the setting of a wide spectrum of systemic disorders. Our aim was to study in vitro effects of CRS Type 5 plasma on renal tubular cells (RTCs, in terms of cellular death and the characterization of inflammatory plasma profile in these patients. Material and Methods. We enrolled 11 CRS Type 5 patients from ICU and 16 healthy controls. Plasma from patients and controls was incubated with renal tubular cells (RTCs and cell death was evaluated. Plasma cytokines were detected. Results. RTCs incubated with CRS Type 5 plasma showed significantly higher apoptosis and necrosis with respect to controls. Plasma cytokine profile of CRS Type 5 patients was significantly different from controls: we observed the production of pro- and anti-inflammatory mediators in these patients. Caspase-3, caspase-8, and caspase-9 were activated in cells treated with CRS Type 5 plasma compared to controls. Conclusions. Our results underline the cytotoxic effect of CRS Type 5 mediators on RTC viability, probably due to the activation of both intrinsic and extrinsic pathways of apoptosis and to the deregulation of cytokine release. The consequence may be the damage of distant organs which lead to the worsening of condition of patients.

  9. Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status.

    Science.gov (United States)

    DE Oliveira, Daiane Teixeira; Savio, Andre Luiz Ventura; Marcondes, Joao Paulo DE Castro; Barros, Tatiane Martins; Barbosa, Ludmila Correia; Salvadori, Daisy Maria Favero; DA Silva, Glenda Nicioli

    2017-03-01

    Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutated cells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survival assay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion, despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role of silibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.

  10. Thymus vulgaris L. extract has antimicrobial and anti-inflammatory effects in the absence of cytotoxicity and genotoxicity.

    Science.gov (United States)

    Oliveira, Jonatas Rafael de; de Jesus Viegas, Daiane; Martins, Ana Paula Réquia; Carvalho, Cláudio Antonio Talge; Soares, Cristina Pacheco; Camargo, Samira Esteves Afonso; Jorge, Antonio Olavo Cardoso; de Oliveira, Luciane Dias

    2017-10-01

    This study evaluated the biological effects of the T. vulgaris L. extract., such as antimicrobial activity on planktonic cultures and mono- and polymicrobial biofilms, cytotoxicity, anti-inflammatory activity and genotoxicity. Monomicrobial biofilms of Candida albicans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and Pseudomonas aeruginosa and polymicrobial biofilms composed by C. albicans with each bacterium were formed for 48h and exposed for 5min to the plant extract. Murine macrophages (RAW 264.7), human gingival fibroblasts (FMM-1), human breast carcinoma cells (MCF-7) and cervical carcinoma cells (HeLa) were also exposed to the plant extract for 5min and the cell viability were analyzed by MTT, neutral red (NR) and crystal violet (CV) assays. Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) produced by RAW 264.7 was quantified by ELISA, after 24h exposure to the plant extract, both in the absence and presence of lipopolysaccharide (LPS) from Escherichia coli. Genotoxicity of the plant extract was evaluated by micronucleus formation (MN) in 1000 cells. The results were analyzed by T-Test or ANOVA and Tukey's Test (P≤0.05). All biofilms showed significant reductions in CFU/mL (colony-forming units per milliliter). Cell viability was above 50% for all cell lines. Anti-inflammatory effect on the synthesis of IL-1β and TNF-α was observed. The MN was similar or lower than the control group in all cells. T. vulgaris L. extract was effective against all biofilms, promoted high cell viability, anti-inflammatory effect and presented no genotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Cytotoxicity of erythrosine (E-127, brilliant blue (E-133 and red 40 (E-129 food dyes in a plant test system - doi: 10.4025/actascibiolsci.v35i4.18419

    Directory of Open Access Journals (Sweden)

    Maria Virna Aguiar de Oliveira

    2013-07-01

    Full Text Available The objective of this work was to evaluate the cytotoxic effect of the food dyes erythrosine, brilliant blue and red 40 on the cell cycle of Allium cepa L. Each dye was evaluated at doses of 0.4 and 4.0 ml, at exposure times of 24 and 48 hours, in onion root tip cells. Cells and the presence of chromosomal aberrations were analyzed throughout the whole cell cycle, totaling 5,000 cells for each group of bulbs. The mitotic index was calculated and the statistical analysis was conducted through the Chi-square test (p < 0.05. From the obtained results, it was verified that the food additives erythrosine and brilliant blue were not cytotoxic to the cells of the test system. However, the red 40 dye, at the two evaluated doses and the two exposure times used in this bioassay have promoted a significant reduction in cell division and induced the emergence of anaphasic and telophasic bridge aberrations and micronucleated cells. Additional cytotoxicity studies should be conducted to add information to these and other previously obtained results in order to evaluate, with property, the action of these three dyes on a cellular level.

  12. Determination and prevention of cytotoxic effects induced in human lymphocytes by the alkylating agent 2,2`-dichlorodiethyl sulfide (sulfur mustard, HD). (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Meier, H.L.; Johnson, J.B.

    1992-12-31

    2,2`-Dichlorodiethyl sulfide (sulfur mustard), HD, 1,1`thiobis(2-chloroethane) is a potent vesicant which can cause severe lesions to skin, lung, and eyes. There is no convenient in vitro or in vivo method(s) to objectively measure the damage induced by HD; therefore, a simple in vitro method was developed using human peripheral lymphocytes to study HD-induced cytotoxicity. The cytotoxicity of HD was measured using dye exclusion as an indicator of human lymphocyte viability. Exposure to HD resulted in both a time- and a concentration-dependent cytotoxic effect on human lymphocytes. Using this in vitro assay, the effectiveness of various therapeutics (niacin, niacinamide, and 3-aminobenzamide) in preventing HD-induced cytotoxicity was studied. Niacinamide and 3-aminobenzamide prevented the cytotoxic effects of HD for up to 2 days.

  13. Anti-biofilm activity of chitosan gels formulated with silver nanoparticles and their cytotoxic effect on human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Pérez-Díaz, M.; Alvarado-Gomez, E. [Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi (Mexico); Magaña-Aquino, M. [Servicio de Epidemiologia del Hospital Central “Dr. Ignacio Morones Prieto”, San Luis Potosi (Mexico); Sánchez-Sánchez, R.; Velasquillo, C. [Laboratorio de Biotecnologia, Instituto Nacional de Rehabilitacion, Mexico, D.F. (Mexico); Gonzalez, C. [Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi (Mexico); Ganem-Rondero, A. [Division de Estudios de Posgrado (Tecnologia Farmaceutica), Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico, Cuautitlan Izcalli, Estado de Mexico (Mexico); Martínez-Castañon, G.; Zavala-Alonso, N. [Doctorado en Ciencias Odontológicas Facultad de Estomatologia, UASLP (Mexico); Martinez-Gutierrez, F. [Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi (Mexico)

    2016-03-01

    The development of multi-species biofilms in chronic wounds is a serious health problem that primarily generates strong resistance mechanisms to antimicrobial therapy. The use of silver nanoparticles (AgNPs) as a broad-spectrum antimicrobial agent has been studied previously. However, their cytotoxic effects limit its use within the medical area. The purpose of this study was to evaluate the anti-biofilm capacity of chitosan gel formulations loaded with AgNPs, using silver sulfadiazine (SSD) as a standard treatment, on strains of clinical isolates, as well as their cytotoxic effect on human primary fibroblasts. Multi-species biofilm of Staphylococcus aureus oxacillin resistant (MRSA) and Pseudomonas aeruginosa obtained from a patient with chronic wound infection were carried out using a standard Drip Flow Reactor (DFR) under conditions that mimic the flow of nutrients in the human skin. Anti-biofilm activity of chitosan gels and SSD showed a log-reduction of 6.0 for MRSA when chitosan gel with AgNPs at a concentration of 100 ppm was used, however it was necessary to increase the concentration of the chitosan gel with AgNPs to 1000 ppm to get a log-reduction of 3.3, while the SSD showed a total reduction of both bacteria in comparison with the negative control. The biocompatibility evaluation on primary fibroblasts showed better results when the chitosan gels with AgNPs were tested even in the high concentration, in contrast with SSD, which killed all the primary fibroblasts. In conclusion, chitosan gel formulations loaded with AgNPs effectively prevent the formation of biofilm and kill bacteria in established biofilm, which suggest that chitosan gels with AgNPs could be used for prevention and treatment of infections in chronic wounds. The statistic significance of the biocompatibility of chitosan gel formulations loaded with AgNPs represents an advance; however further research and development are necessary to translate this technology into therapeutic and

  14. Cytotoxic effect of some medicinal plants from Asteraceae family on J-45.01 leukemic cell line--pilot study.

    Science.gov (United States)

    Wegiera, Magdalena; Smolarz, Helena D; Jedruch, Marcin; Korczak, Magdalena; Koproń, Kamila

    2012-01-01

    In this study the in vitro cytotoxic properties of ethanol extracts from the herbs, inflorescents and roots of selected Asteraceae species: Arctium lappa, Artemisia absinthium, Calendula officinalis, Centaurea cyanus, Tanacetum vulgare and Tragopogon pratensis on J-45.01 human acute T leukemia cell line was examined. All tested samples possess antileukemic properties and induce cells death via apoptosis. The correlation between antileukemic activity and total polyphenol content was determined.

  15. Cytotoxic effects of alkaloids on cervical carcinoma cell lines: a review

    Directory of Open Access Journals (Sweden)

    Priscilla Alencar Fernandes

    2016-07-01

    Full Text Available Cervical cancer is the fourth type of women neoplasia, with thousands of new cases annually. It is closely related to human papillomavirus (HPV infection, which has more than 13 oncogenic types, among them HPV 16 and 18 are implicated in 70% of cervical carcinoma cases. Alkaloids are nitrogenated and naturally occurring compounds, showing several uses in medical treatment, including cytotoxic and antineoplastic activities. In this work we aim to evaluate the cytotoxic and chemotherapeutic potential of alkaloids against cervical cancer. In order to accomplish this purpose, we have made a survey of potentially effective alkaloids with cytotoxic activities over HPV-16+ and HPV-18 + cells (HeLa cells. Through a literature review between the years of 1980 and 2015, we described the major alkaloid sources, distribution in nature and also discussed the mechanisms of action for their cytotoxicity. We found that alkaloids showed efficacy as cytotoxic agents, inhibiting cell growth of the HPV-transformed cells in vitro and in vivo by means of activation of intrinsic and extrinsic pathways of apoptosis, which included the clivage of caspases and PARP-1 (Poli-Adenosyl- Ribose Protease 1, increase in p53 expression, release of cytochrome C and increase of cell death receptors expression like Fas, mainly observed in HeLa (HPV- 18 + cell lines. Moreover, these secondary metabolites helped in modulating the MDR (Multi-Drug Resistance against the cell lines studied, which lead us to suggest their possible use as chemotherapeutic agents on the lesions caused by these virusesKeywords: Cervical cancer. Alkaloids. HPV. Chemotherapy. RESUMOEfeitos citotóxicos de alcaloides sobre linhagens de células do câncer cervical: uma revisãoO câncer cervical é a quarta neoplasia incidente em mulheres, com o surgimento de milhares de novos casos anualmente. Está altamente relacionado à infecção pelo papilomavírus humano (HPV, que apresenta mais de 13 tipos oncog

  16. Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity

    Science.gov (United States)

    Munnier, E.; Cohen-Jonathan, S.; Hervé, K.; Linassier, C.; Soucé, M.; Dubois, P.; Chourpa, I.

    2011-03-01

    The clinical use of the anticancer drug doxorubicin (DOX) is limited by strong side effects and phenomena of cell resistance. Drug targeting by binding DOX to nanoparticles could overcome these limitations. We recently described a method to associate DOX to superparamagnetic iron oxide nanoparticles (SPION) in view of magnetic drug targeting (Munnier et al. in Int J Pharm 363:170-176, 2008). DOX is bound to the nanoparticle surface through a pre-formed DOX-Fe2+ complex. The DOX-loaded SPION present interesting properties in terms of drug loading and biological activity in vitro. The purpose of this study is to explore the possible mechanisms of the in vitro cytotoxicity of DOX-loaded SPION. The uptake of SPION was followed qualitatively by conventional optical microscopy after Prussian blue staining and quantitatively by iron determination by atomic absorption spectroscopy. The subcellular distribution of intrinsically fluorescent DOX was followed by confocal spectral imaging (CSI) and the subsequent cytotoxicity by the MTT method. We reveal modifications of DOX intracellular interactions for SPION-delivered drug and increased cytotoxicity. These results are discussed in terms of internalization route of the drug and of a potential role of iron oxide nanoparticles in the observed cytotoxicity.

  17. Green synthesis of silver nanoparticles using Lippia nodiflora aerial extract and evaluation of their antioxidant, antibacterial and cytotoxic effects

    Directory of Open Access Journals (Sweden)

    Arumugam Sudha

    2017-12-01

    Full Text Available Silver nanoparticles biosynthesis has received increasing attention in the field of nanotechnology due to their antimicrobial and biomedical applications. Green synthesis of metal nanoparticles is anticipated as a cost effective and eco-friendly alternative in the current research scenario. With this aim, the aqueous extracts made from the aerial parts of Lippia nodiflora were used as the reducing agents to synthesize silver nanoparticles (AgNPs and their antioxidant, antibacterial and cytotoxic properties have also been evaluated. The biosynthesized AgNPs were characterized by UV–Visible Spectroscopy, Fourier-Transform Infrared Spectroscopy (FTIR and X-Ray Diffraction (XRD analysis. The AgNPs were found to be stable at −25.2 mV through zeta potential study. The morphology and size of synthesized silver nanoparticles were confirmed by Scanning Electron Microscope with energy dispersive spectra (SEM-EDX and Transmission Electron Microscopy (TEM analysis with size range from 30 to 60 nm. Biosynthesized AgNPs exhibited strong antioxidant activity as well as showed potent antibacterial activity against human pathogenic bacteria. The cytotoxicity study of AgNPs was also revealed against MCF-7 breast cancer cell lines in a dose-dependent manner. The recognized bioactivity confirmed by the synthesized AgNPs directs towards the clinical use as an antioxidant, antibacterial and cytotoxic agent. Keywords: Lippia nodiflora, Silver nanoparticles, SEM, Antioxidant, Antibacterial, Cytotoxicity

  18. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of a natural antidepressant, Hypericum perforatum L. (St. John's wort), on vegetal and animal test systems.

    Science.gov (United States)

    Peron, Ana Paula; Mariucci, Rosinete Gonçalves; de Almeida, Igor Vivian; Düsman, Elisângela; Mantovani, Mário Sérgio; Vicentini, Veronica Elisa Pimenta

    2013-05-06

    St. John's wort (Hypericum perforatum L.) is an herbaceous plant that is native to Europe, West Asia and North Africa and that is recognized and used worldwide for the treatment of mild and moderate depression. It also has been shown to be therapeutic for the treatment of burns, bruises and swelling and can be used for its wound healing, antiviral, antimicrobial, antioxidant, analgesic, hepato-protective and anxiolytic properties. The aim of this study was to evaluate the potential cytotoxic, mutagenic and antimutagenic action of H. Perforatum. Meristematic cells were used as the test system for Allium cepa L., and bone marrow cells from Rattus norvegicus, ex vivo, were used to calculate the mitotic index and the percentage of chromosomal aberration. Statistical analysis was performed using the chi-square test. This medicinal plant had no cytotoxic potential in the vegetal test system evaluated. In the animal test system, none of the acute treatments, including intraperitoneal gavage and subchronic gavage, were cytotoxic or mutagenic. Moreover, this plant presented antimutagenic activity against the clastogenic action of cyclophosphamide, as confirmed in pre-treatment (76% reduction in damage), simultaneous treatment (95%) and post-treatment (97%). Thus, the results of this study suggest that the administration of H. perforatum, especially by gavage similar to oral consumption used by humans, is safe and with beneficial antimutagenic potential.

  19. The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp.

    Science.gov (United States)

    Alizadehnohi, Masoumehzaman; Nabiuni, Mohammad; Nazari, Zahra; Safaeinejad, Zahra; Irian, Saeed

    2012-01-01

    Ovarian cancer is considered to be one of the most important causes of death among women. Cisplatin is one of the oldest chemotherapeutical compounds used for treating ovarian cancer. Previous studies have shown the inhibitory effects of bee venom on certain types of cancer. The aim of the present study was to evaluate the cytotoxic effect of bee venom alone and its synergistic cytological effects in combination with cisplatin on ovarian cancerous cisplatin resistant A2780cp cells. To investigate the cytotoxic effect of bee venom on A2780cp cells and its synergetic effect with cisplatin, MTT assay, morphological examination, DNA fragmentation assay, flowcytometric and immunocytochemical analysis were performed. MTT assay revealed that 8µg/ml bee venom, 25mg/ml cisplatin and 4µg/ml bee venom/10mg/ml cisplatin cause an approximately 50% A2780cp cell death after 24hr. Morphological and biochemical analysis indicated an apoptotic type of cell death induced by bee venom and cisplatin, separately and in combination. Immunocytochemistry demonstrated a reduction in the levels of the Bcl2 protein. Overall, our findings suggest that components of bee venom may exert an anti-tumor effect on human ovarian cancer and that has the potential for enhancing the cytotoxic effect of the antitumor agent cisplatin.

  20. Silencing the livin gene enhances the cytotoxic effects of anticancer drugs on colon cancer cells.

    Science.gov (United States)

    Oh, Bo Young; Kim, Kwang Ho; Chung, Soon Sup; Lee, Ryung-Ah

    2016-12-01

    Livin is associated with drug response in several cancers. The aim of this study was to investigate the effect of silencing the livin gene expression on anticancer drug response in colorectal cancer. siRNA was transfected at different concentrations (0, 10, and 30nM) into HCT116 cells, then cells were treated with either 5-fluorouracil (FU)/leucovorin (LV) or oxaliplatin (L-OHP)/5-FU/LV. Cellular viability and apoptosis were evaluated following silencing of livin gene expression combined with treatment with anticancer drugs. Livin gene expression was effectively suppressed by 30nM siRNA compared with control and 10nM siRNA. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that proliferation was effectively inhibited in cells treated with a combination of both siRNA and an anticancer drug, compared to cells treated with siRNA-Livin or anticancer drug alone. In particular, the combination of 30nM siRNA and L-OHP/5-FU/LV resulted in a 93.8% and 91.4% decrease, compared to untreated control or L-OHP/5-FU/LV alone, respectively. Cellular proliferation was most effectively suppressed by a combination of 30nM of siRNA and L-OHP/5-FU/LV compared to other combinations. siRNA-mediated down-regulation of livin gene expression could significantly suppress colon cancer growth and enhance the cytotoxic effects of anticancer drugs such as 5-FU and L-OHP. The results of this study suggest that silencing livin gene expression in combination with treatment with anticancer drugs might be a novel cancer therapy for colorectal cancer.

  1. Heparin-anthranoid conjugates associated with nanomagnetite particles and their cytotoxic effect on cancer cells.

    Science.gov (United States)

    Durdureanu-Angheluta, Anamaria; Uritu, Cristina M; Coroaba, Adina; Minea, Bogdan; Doroftei, Florica; Calin, Manuela; Maier, Stelian Sergiu; Pinteala, Mariana; Simionescu, Maya; Simionescu, Bogdan C

    2014-01-01

    The paper describes a methodology for preparing monodisperse, water-soluble magnetite nanoparticles, coated with heparin and loaded with 4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid (Rhein), able to be used as a drug delivery system for cancer chemotherapy. Upon preparation, nanoparticles structure and morphology were investigated. The surface charge and the equivalent dimensions of the nanoparticles dispersed in water were measured, as a function of the suspension pH. The concentration of the drug into the nanoparticles shell, and the drug release profile was determined. The functionality of Rhein-loaded heparin-coated magnetic nanoparticles was assessed by monitoring their cytotoxic effect on cultured human tumor hepatocyte cell line, HepG2, using MTT assay. We found that upon exposure of HepG2 cells to Rhein-loaded heparin-coated nanoparticles, the cell viability was drastically reduced (to approximately 10%) as compared to that of the cells exposed to the free drug, indicating the potential of these magnetite nanoparticles to be used in cancer therapy.

  2. Biosynthesis, characterization and cytotoxic effect of plant mediated silver nanoparticles using Morinda citrifolia root extract.

    Science.gov (United States)

    Suman, T Y; Radhika Rajasree, S R; Kanchana, A; Elizabeth, S Beena

    2013-06-01

    Silver has been used since time to control bodily infection, prevent food spoilage and heal wounds by preventing infection. The present study aims at an environmental friendly method of synthesizing silver nanoparticles, from the root of Morinda citrifolia; without involving chemical agents associated with environmental toxicity. The obtained nanoparticles were characterized by UV-vis absorption spectroscopy with an intense surface plasmon resonance band at 413 nm clearly reveals the formation of silver nanoparticles. Fourier transmission infra red spectroscopy (FTIR) showed nanopartilces were capped with plant compounds. Field emission-scanning electron microscopy (FE-SEM) and Transmission electron microscopy (TEM) showed that the spherical nature of the silver nanoparticles with a size of 30-55 nm. The X-ray diffraction spectrum XRD pattern clearly indicates that the silver nanoparticles formed in the present synthesis were crystalline in nature. In addition these biologically synthesized nanoparticles were also proved to exhibit excellent cytotoxic effect on HeLa cell. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang Fanjie

    2009-09-01

    Full Text Available Background: Accelerated glucose uptake for anerobic glycolysis is one of the major metabolic changes found in malignant cells. This property has been exploited for imaging malignancies and as a possible anticancer therapy. The nonmetabolizable glucose analog 2-deoxyglucose (2 DG interferes with glucose metabolism leading to breast cancer cell death. Aims: To determine whether 2DG can synergize with chemotherapeutic agents commonly used in breast cancer treatment and identify cellular characteristics associated with sensitivity to 2DG. Materials and Methods: SkBr3 breast cancer cells were incubated with varying concentrations of 5-fluorouracil (5FU, doxorubicin, cisplatin, cyclophosphamide, or herceptin with or without 2DG. Cell viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results: Combining 2DG with doxorubicin, 5 FU, cyclophosphamide, and herceptin resulted in enhanced cell death compared with each agent alone, while in combination with cisplatin, the amount of cell death was additive. Mouse embryo fibroblasts (MEF mutated for p53 (-/- were 30% more sensitive to the cytotoxic effects of 2DG than the parental cell lines. Cells mutated for Bax/Bac, genes involved in protection from apoptosis, are slightly more sensitive than the parental cell lines. Conclusions: These results indicate that 2DG acts synergistically with specific chemotherapeutic agents in causing cell death and the class of chemicals most sensitive appear to be those which cause DNA damage.

  4. In vitro evaluation of selenium genotoxic, cytotoxic, and protective effects: a review

    Energy Technology Data Exchange (ETDEWEB)

    Valdiglesias, Vanessa [University of A Coruna, Toxicology Unit, Department of Psychobiology, A Coruna (Spain); University of A Coruna, Department of Cell and Molecular Biology, Faculty of Sciences, A Coruna (Spain); Pasaro, Eduardo; Laffon, Blanca [University of A Coruna, Toxicology Unit, Department of Psychobiology, A Coruna (Spain); Mendez, Josefina [University of A Coruna, Department of Cell and Molecular Biology, Faculty of Sciences, A Coruna (Spain)

    2010-05-15

    Selenium is an oligoelement with essential biological functions. Diet is the most important selenium source, and intake of this element depends on its concentration in food and amount of food consumed. Among the essential human micronutrients, selenium is peculiar due to its beneficial physiological activity and toxicity. It may have anticarcinogenic effects at low concentrations, whereas at concentrations higher than those necessary for nutrition, it can be genotoxic and carcinogenic. Because of that, selenium is probably the most widely investigated of all the oligonutrients. In the last decades, there has been increasing interest in several nutritional Se compounds because of their environmental, biological, and toxicological properties, particularly for their cancer- and disease-preventing activities. This article gives an overview of the results of in vitro studies on mutagenicity, genotoxicity, cytotoxicity, and DNA repair conducted within the last decades with different organic and inorganic selenium compounds. Results from these studies provide a better knowledge on the selenium activity and help to elucidate the reasons underlying its duality in order to regulate its correct use in nutrition and clinic. (orig.)

  5. L-Leucine for gold nanoparticles synthesis and their cytotoxic effects evaluation.

    Science.gov (United States)

    Berghian-Grosan, Camelia; Olenic, Liliana; Katona, Gabriel; Perde-Schrepler, Maria; Vulcu, Adriana

    2014-11-01

    This work reports the preparation of water-soluble leucine capped gold nanoparticles by two single-step synthesis methods. The first procedure involves a citrate reduction approach where the citrate is used as reducing agent and leucine as capping/stabilizing agent. Different sizes of gold nanoparticles, citrate reduced and stabilized by leucine, Leu-AuNPs-C, with the mean diameters in the range of 21-56 nm, were obtained by varying the macroscopic parameters such as: concentration of the gold precursor solution, Au (III):citrate molar ratio and leucine pH. In the second procedure, leucine acts both as reducing and stabilizing agent, allowing us to obtain spherical gold nanoparticles, Leu-AuNPs, with a majority of 80 % (with the mean diameter of 63 nm). This proves that leucine is an appropriate reductant for the formation of water-soluble and stable gold nanoparticles colloids. The characterization of the leucine coated gold nanoparticles was carried out by TEM, UV-Vis and FT-IR analysis. The cytotoxic effect of Leu-AuNPs-C and Leu-AuNPs was also evaluated.

  6. Comparison of the cytotoxic effect of polystyrene latex nanoparticles on planktonic cells and bacterial biofilms

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Toshiyuki, E-mail: nomura@chemeng.osakafu-u.ac.jp; Fujisawa, Eri; Itoh, Shikibu; Konishi, Yasuhiro [Osaka Prefecture University, Department of Chemical Engineering (Japan)

    2016-06-15

    The cytotoxic effect of positively charged polystyrene latex nanoparticles (PSL NPs) was compared between planktonic bacterial cells and bacterial biofilms using confocal laser scanning microscopy, atomic force microscopy, and a colony counting method. Pseudomonas fluorescens, which is commonly used in biofilm studies, was employed as the model bacteria. We found that the negatively charged bacterial surface of the planktonic cells was almost completely covered with positively charged PSL NPs, leading to cell death, as indicated by the NP concentration being greater than that required to achieve single layer coverage. In addition, the relationship between surface coverage and cell viability of P. fluorescens cells correlated well with the findings in other bacterial cells (Escherichia coli and Lactococcuslactis). However, most of the bacterial cells that formed the biofilm were viable despite the positively charged PSL NPs being highly toxic to planktonic bacterial cells. This indicated that bacterial cells embedded in the biofilm were protected by self-produced extracellular polymeric substances (EPS) that provide resistance to antibacterial agents. In conclusion, mature biofilms covered with EPS exhibit resistance to NP toxicity as well as antibacterial agents.

  7. Cytotoxic effects of gamma radiation and DEET on Perna perna mussels

    Energy Technology Data Exchange (ETDEWEB)

    Martini, Gisela A.; Rogero, Sizue O.; Silva, Marina V.; Rogero, Jose Roberto, E-mail: gisela.martini@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Aiming at the protection of aquatic biota becomes desirable progress in identifying and quantifying the presence of chemical contaminants to an evaluation of its bioavailability and harmful effects to the aquatic ecosystem. Diethyltoluamide (DEET) is one of the most commonly used active ingredients in insect repellents and is considered an emergent contaminant. In addition the environment in regions near nuclear facilities (mostly coastal) and in regions with higher level of background radiation, many aquatic organisms could be exposed to radiation, becoming more susceptible to other contaminants. Therefore, the purpose of this study was the investigation of the biological effects of ionizing radiation in combination with the exposure of Perna perna mussels to DEET. Previously it was determined the doses of {sup 60}Co gamma radiation (3 and 107 Gy) and the DEET concentrations (0.02 and 0.001mg L-1) which causes cytotoxicity in lysosomes of Perna perna mussels hemocytes. The effects were evaluated by the neutral red retention time assay in irradiated and non-irradiated organisms. The assays were performed in 72 hours, with readings on each 24 hours. The endpoint was the lysosome membrane disruption causing the decrease of the neutral red retention time observed . The results showed that was no statistic difference of irradiated organisms with 3 Gy and exposed to different concentrations of DEET in comparison with non-irradiated organisms, the mean neutral red retention time in assays was around 40 minutes. The organisms that were exposed to DEET after 107 Gy irradiation dose showed cell lysis and neutral red retention time less than 30 minutes, this suggests that synergistic effect can be observed depending on the irradiated dose and the DEET concentration. (author)

  8. Cytotoxic, Antiproliferative and Pro-Apoptotic Effects of 5-Hydroxyl-6,7,3′,4′,5′-Pentamethoxyflavone Isolated from Lantana ukambensis

    Directory of Open Access Journals (Sweden)

    Wamtinga Richard Sawadogo

    2015-12-01

    Full Text Available Lantana ukambensis (Vatke Verdc. is an African food and medicinal plant. Its red fruits are eaten and highly appreciated by the rural population. This plant was extensively used in African folk medicinal traditions to treat chronic wounds but also as anti-leishmanial or cytotoxic remedies, especially in Burkina Faso, Tanzania, Kenya, or Ethiopia. This study investigates the in vitro bioactivity of polymethoxyflavones extracted from a L. ukambensis as anti-proliferative and pro-apoptotic agents. We isolated two known polymethoxyflavones, 5,6,7,3′,4′,5′-hexamethoxyflavone (1 and 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 from the whole plant of L. ukambensis. Their chemical structures were determined by spectroscopic analysis and comparison with published data. These molecules were tested for the anti-proliferative, cytotoxic and pro-apoptotic effects on human cancer cells. Among them, 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 was selectively cytotoxic against monocytic lymphoma (U937, acute T cell leukemia (Jurkat, and chronic myelogenous leukemia (K562 cell lines, but not against peripheral blood mononuclear cells (PBMCs from healthy donors, at all tested concentrations. Moreover, this compound exhibited significant anti-proliferative and pro-apoptotic effects against U937 acute myelogenous leukemia cells. This study highlights the anti-proliferative and pro-apoptotic effects of 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 and provides a scientific basis of traditional use of L. ukambensis.

  9. Comparative cytotoxicity of periodontal bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, R.H.; Hammond, B.F.

    1988-11-01

    The direct cytotoxicity of sonic extracts (SE) from nine periodontal bacteria for human gingival fibroblasts (HGF) was compared. Equivalent dosages (in terms of protein concentration) of SE were used to challenge HGF cultures. The cytotoxic potential of each SE was assessed by its ability to (1) inhibit HGF proliferation, as measured by direct cell counts; (2) inhibit 3H-thymidine incorporation in HGF cultures; or (3) cause morphological alterations of the cells in challenged cultures. The highest concentration (500 micrograms SE protein/ml) of any of the SEs used to challenge the cells was found to be markedly inhibitory to the HGFs by all three of the criteria of cytotoxicity. At the lowest dosage tested (50 micrograms SE protein/ml); only SE from Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, and Fusobacterium nucleatum caused a significant effect (greater than 90% inhibition or overt morphological abnormalities) in the HGFs as determined by any of the criteria employed. SE from Capnocytophaga sputigena, Eikenella corrodens, or Wolinella recta also inhibited cell proliferation and thymidine incorporation at this dosage; however, the degree of inhibition (5-50%) was consistently, clearly less than that of the first group of three organisms named above. The SE of the three other organisms tested (Actinomyces odontolyticus, Bacteroides intermedius, and Streptococcus sanguis) had little or no effect (0-10% inhibition) at this concentration. The data suggest that the outcome of the interaction between bacterial components and normal resident cells of the periodontium is, at least in part, a function of the bacterial species.

  10. Biological effects of a de novo designed myxoma virus peptide analogue: evaluation of cytotoxicity on tumor cells.

    Directory of Open Access Journals (Sweden)

    Taghrid S Istivan

    Full Text Available BACKGROUND: The Resonant Recognition Model (RRM is a physico-mathematical model that interprets protein sequence linear information using digital signal processing methods. In this study the RRM concept was employed for structure-function analysis of myxoma virus (MV proteins and the design of a short bioactive therapeutic peptide with MV-like antitumor/cytotoxic activity. METHODOLOGY/PRINCIPAL FINDINGS: The analogue RRM-MV was designed by RRM as a linear 18 aa 2.3 kDa peptide. The biological activity of this computationally designed peptide analogue against cancer and normal cell lines was investigated. The cellular cytotoxicity effects were confirmed by confocal immunofluorescence microscopy, by measuring the levels of cytoplasmic lactate dehydrogenase (LDH and by Prestoblue cell viability assay for up to 72 hours in peptide treated and non-treated cell cultures. Our results revealed that RRM-MV induced a significant dose and time-dependent cytotoxic effect on murine and human cancer cell lines. Yet, when normal murine cell lines were similarly treated with RRM-MV, no cytotoxic effects were observed. Furthermore, the non-bioactive RRM designed peptide RRM-C produced negligible cytotoxic effects on these cancer and normal cell lines when used at similar concentrations. The presence/absence of phosphorylated Akt activity in B16F0 mouse melanoma cells was assessed to indicate the possible apoptosis signalling pathway that could be affected by the peptide treatment. So far, Akt activity did not seem to be significantly affected by RRM-MV as is the case for the original viral protein. CONCLUSIONS/SIGNIFICANCE: Our findings indicate the successful application of the RRM concept to design a bioactive peptide analogue (RRM-MV with cytotoxic effects on tumor cells only. This 2.345 kDa peptide analogue to a 49 kDa viral protein may be suitable to be developed as a potential cancer therapeutic. These results also open a new direction to the rational

  11. Chemical composition, cytotoxicity effect and antimicrobial activity of Ceratonia siliqua essential oil with preservative effects against Listeria inoculated in minced beef meat.

    Science.gov (United States)

    Hsouna, Anis Ben; Trigui, Mohamed; Mansour, Riadh Ben; Jarraya, Raoudha Mezghani; Damak, Mohamed; Jaoua, Samir

    2011-07-15

    The present study describes the phytochemical profile and the protective effects of Ceratonia siliqua pods essential oil (CsEO), a food and medicinal plant widely distributed in Tunisia. Twenty five different components were identified in the CsEO. Among them, the major detected components were: Nonadecane, Heneicosane , Naphthalene, 1,2-Benzenedicarboxylic acid dibutylester, Heptadecane, Hexadecanoic acid, Octadecanoic acid, 1,2-Benzenedicarboxylic acid, Phenyl ethyl tiglate, Eicosene, Farnesol 3, Camphor, Nerolidol and n-Eicosane. The antimicrobial activity of CsEO was evaluated against a panel of 13 bacteria and 8 fungal strains using agar diffusion and broth microdilution methods. Results have shown that CsEO exhibited moderate to strong antimicrobial activity against the tested species. In addition, the inhibitory effect of this CsEO was evaluated in vivo against a foodborne pathogens Listeria monocytogenes, experimentally inoculated in minced beef meat (2×10(2) CFU/g of meat) amended with different concentrations of the CsEO and stored at 7 °C for 10 days. The antibacterial activity of CsEO in minced beef meat was clearly evident and its presence led to a strong inhibitory effect against the pathogens at 7 °C. On the other hand, the cytotoxic effects of the essential oil against two tumoral human cell lines HeLa and MCF-7 were examined by MTT assay. The CsEO showed an inhibition of both cell lines with significantly stronger activity against HeLa cells. The IC(50) values were 210 and 800 μg/ml for HeLa and MCF-7 cells, respectively. Overall, results presented here suggest that the EO of C. siliqua possesses antimicrobial and cytotoxic properties, and is therefore a potential source of active ingredients for food and pharmaceutical industry. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Sensitivity of different cytotoxic responses of Vero cells exposed to organic chemical pollutants and their reliability in the bio-toxicity test of trace chemical pollutants.

    Science.gov (United States)

    Liao, Ting-Ting; Shi, Yan-Ling; Jia, Jian-Wei; Wang, Lei

    2010-06-01

    To find a sensitive cytotoxic response to reflect the bio-toxicity of trace organic pollutants, the sensitivity and reliability of morphological change and proliferation inhibition of Vero cells exposed to 2, 4, 6-trichlorophenol (TCP) and the leachate from products related to drinking water (PRDW) were compared, and the mechanism of the morphological change in Vero cells exposed to chemical pollutants was studied. Vero cells were treated by different concentration of TCP and the leachate from PRDW. Methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay was carried out for proliferation inhibition. Bioluminescence method was carried out as another method to test the toxicity of TCP. Flow Cytometry assay was used to test cell Apoptosis and damage of cell-membrane. 0.25 mg/L TCP had an effect on cell morphology, and the proportion of morphologically changed cells increased with increasing TCP concentration. At low TCP concentrations, inhibition of cell proliferation did not seem to correlate to TCP concentration, and was negative when TCP concentration was cells increased with extracting temperature, but the inhibition of cell proliferation failed to reflect the correlation between extracting temperature and proliferation inhibition of Vero cells. Although the Sensitivity of bioluminescence method seems to be similar to morphological change in Vero cells, the bacterial in this method is not homologous enough with human body cells to reflect the toxicity to human body. These imply cell morphological change is a more sensitive and reliable method to reflect bio-toxicity of organic pollutants than proliferation inhibition. Flow cytometry analysis and cell rejuvenation experiments indicated cell membrane damage, which results in cell morphological change, was an early and sensitive cytotoxic response comparing with necrosis. These results indicated that the cell membrane toxicity represented by morphological changes is a more sensitive and reliable method to

  13. The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein

    Directory of Open Access Journals (Sweden)

    Kobayashi Natsuki

    2010-05-01

    Full Text Available Abstract Background Parkinson's disease (PD involves the selective damage of dopaminergic neuron cells resulting from the accumulation and fibril formation of alpha-synuclein. Recently, it has been shown that not only full-length alpha-synuclein, but also C-terminal truncated forms exist in the normal brain, as well as Lewy bodies, which are cytoplasmic inclusions in PD. It is known that truncated alpha-synuclein has a much higher ability to aggregate and fibrillate than full-length alpha-synuclein. Since the fibrils and precursor oligomers of alpha-synuclein are cytotoxic to the neuron, inhibitors that prevent the formation of oligomers and/or fibrils might open the way to a novel therapeutic approach to PD. However, no inhibitor for truncated alpha-synuclein has been reported yet. Results In this study, we first characterized the aggregation and cytotoxicity of C-truncated alpha-synuclein119 and alpha-synuclein133 which have been found in both the normal and the pathogenic brain. Alpha-synuclein119 aggregated more rapidly and enhanced significantly the fibril formation of alpha-synuclein. Although both of alpha-synuclein119 and alpha-synuclein133 showed a high cytotoxicity, alpha-synuclein133 showed a similar aggregation with full-length alpha-synuclein and no acceleration effect. We showed that PQQ dramatically inhibits the fibril formation of C-terminal truncated alpha-synuclein110119, and 133 as well as the mixtures of full-length alpha-synuclein with these truncated variants. Moreover, PQQ decreases the cytotoxicity of truncated alpha-synuclein. Conclusions Our results demonstrate that PQQ inhibits the amyloid fibril formation and cytotoxicity of the C-truncated alpha-synuclein variants. We believe that PQQ is a strong candidate for a reagent compound in the treatment of PD.

  14. Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity.

    Science.gov (United States)

    Al-Abbasi, Fahad A; Alghamdi, Eman A; Baghdadi, Mohammed A; Alamoudi, Abdulmohsin J; El-Halawany, Ali M; El-Bassossy, Hany M; Aseeri, Ali H; Al-Abd, Ahmed M

    2016-07-08

    Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl₄-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4'-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC50 values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG₂ and Huh7, cells decreasing its IC50s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G₂/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G₂/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM) was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics.

  15. Dissolution effect and cytotoxicity of diamond-like carbon coatings on orthodontic archwires.

    Science.gov (United States)

    Kobayashi, Shinya; Ohgoe, Yasuharu; Ozeki, Kazuhide; Hirakuri, Kenji; Aoki, Hideki

    2007-12-01

    Nickel-titanium (NiTi) has been used for implants in orthodontics due to the unique properties such as shape memory effect and superelasticity. However, NiTi alloys are eroded in the oral cavity because they are immersed by saliva with enzymolysis. Their reactions lead corrosion and nickel release into the body. The higher concentrations of Ni release may generate harmful reactions. Ni release causes allergenic, toxic and carcinogenic reactions. It is well known that diamond-like carbon (DLC) films have excellent properties, such as extreme hardness, low friction coefficients, high wear resistance. In addition, DLC film has many other superior properties as a protective coating for biomedical applications such as biocompatibility and chemical inertness. Therefore, DLC film has received enormous attention as a biocompatible coating. In this study, DLC film coated NiTi orthodontic archwires to protect Ni release into the oral cavity. Each wire was immersed in physiological saline at the temperature 37 degrees C for 6 months. The release concentration of Ni ions was detected using microwave induced plasma mass spectrometry (MIP-MS) with the resolution of ppb level. The toxic effect of Ni release was studied the cell growth using squamous carcinoma cells. These cells were seeded in 24 well culture plates and materials were immersed in each well directly. The concentration of Ni ions in the solutions had been reduced one-sixth by DLC films when compared with non-coated wire. This study indicated that DLC films have the protective effect of the diffusion and the non-cytotoxicity in corrosive environment.

  16. Effect of Digestion and Storage of Human Milk on Free Fatty Acid Concentration and Cytotoxicity

    Science.gov (United States)

    Penn, Alexander H.; Altshuler, Angelina E.; Small, James W.; Taylor, Sharon F.; Dobkins, Karen R.; Schmid-Schönbein, Geert W.

    2014-01-01

    Objectives Fat is digested in the intestine into free fatty acids (FFAs), which are detergents and therefore toxic to cells at micromolar concentration. The mucosal barrier protects cells in the adult intestine, but this barrier may not be fully developed in premature infants. Lipase-digested infant formula, but not fresh human milk, has elevated FFAs and is cytotoxic to intestinal cells, and therefore could contribute to intestinal injury in necrotizing enterocolitis (NEC). But even infants exclusively fed breast milk may develop NEC. Our objective was to determine if stored milk and milk from donor milk banks (DM) could also become cytotoxic, especially after digestion. Methods We exposed cultured rat intestinal epithelial cells or human neutrophils to DM and milk collected fresh and stored at 4 or −20 °C for up to 12 weeks and then treated for 2 hours (37°C) with 0.1 or 1 mg/ml pancreatic lipase and/or trypsin and chymotrypsin. Results DM and milk stored 3 days (at 4 or −20 °C) and then digested were cytotoxic. Storage at −20 °C for 8 and 12 weeks resulted in an additional increase in cytotoxicity. Protease digestion decreased, but did not eliminate cell death. Conclusions Current storage practices may allow milk to become cytotoxic and contribute to intestinal damage in NEC. PMID:24840512

  17. Effects of single and multiple flavonoids on BCRP-mediated accumulation, cytotoxicity and transport of mitoxantrone in vitro.

    Science.gov (United States)

    An, Guohua; Morris, Marilyn E

    2010-07-01

    The objective of our study was to investigate the effect of single and multiple flavonoids on the accumulation and cytotoxicity of mitoxantrone in BCRP-overexpressing breast cancer cells and on the transport of mitoxantrone in BCRP-expressing normal cells. The effect of flavonoids on mitoxantrone accumulation and cytotoxicity was studied in the human breast cancer MCF-7 MX100 cell line. Mitoxantrone transport in the presence of flavonoids was studied in human and murine BCRP-transfected MDCK cell lines, and mitoxantrone concentrations were determined by HPLC. Our results demonstrated that multiple flavonoid combinations act additively and exhibit strong BCRP inhibition for increasing mitoxantrone accumulation in breast cancer cells. Kaempferide, biochanin A, 5,7-dimethoxyflavone, and 8-methylflavone greatly increased the cytotoxicity of mitoxantrone in BCRP-overexpressing breast cancer cells. Additionally, the basolateral-to-apical membrane-directed transport of mitoxantrone in murine Bcrp1- and human BCRP-expressing MDCK cells, in the presence of 2.5 microM of these flavonoids, was also significantly decreased. The results indicate that flavonoids are potent BCRP inhibitors and that they exert additive effects when used in combination. Flavonoids demonstrate MDR-reversing effects, but also may influence the disposition of mitoxantrone and cause pharmacokinetic interactions.

  18. Cytotoxic and apoptotic effects of different extracts of Artemisia biennis Willd. on K562 and HL-60 cell lines

    Directory of Open Access Journals (Sweden)

    Zahra Tayarani-Najaran

    2017-02-01

    Full Text Available Objective(s: Artemisia is a genus of herbs and small shrubs forms an important part of natural vegetation in Iran. It has been reported that several Artemisia species possess anti-proliferative effects. Considering the value of this genus in anti-cancer researches we have chosen Artemisia biennis for cytotoxic and mechanistic studies. Materials and Methods:In this study we have investigated the cytotoxic and apoptotic effects of petroleum ether, dichloromethane, ethyl acetate, ethanol, and ethanol:water (1:1 v/v extracts of A. biennis Willd. on two cancer human cell lines (K562 and HL-60 and J774 as normal cells. Results: CH2Cl2 extract was found to have the highest anti-proliferative effect on cancer cells. IC50 values obtained in AlamarBlue® assay for CH2Cl2 extract were 64.86 and 54.31 µg/ml on K562 and HL-60 cells respectively. In flow cytometry histogram of the cells treated with CH2Cl2 extract, sub-G1 peak was induced. DNA fragmentation, increased in the level of Bax and cleavage of PARP protein all showed the induction of apoptosis with CH2Cl2 extract after 48 hr contact with cells. Conclusion: The results can corroborate the cytotoxic and apoptotic effects of the CH2Cl2 extract of A. biennis on the K562 and HL-60 cancer cell lines.

  19. Antimicrobial Activity of Hippurate Nanocomposite and Its Cytotoxicity Effect in Combination with Cytarabine against HL-60

    Directory of Open Access Journals (Sweden)

    Samer Hasan Hussein Al Ali

    2013-01-01

    Full Text Available Hippuric acid (HA was intercalated into a zinc-layered hydroxide (ZLH by direct reaction of an aqueous suspension of zinc oxide with an aqueous solution of hippuric acid to obtain hippurate nanocomposite (HAN. Various concentrations of hippuric acid (0.05, 0.2, and 0.4 molar were used for the synthesis of the nanocomposite. The as-synthesized HAN using 0.2 molar was found to give a well-ordered layered nanocomposite material with an increase in the basal spacing to 21.3 Å which indicated the insertion of hippurate organic moiety into the ZLH interlayers. The cytotoxicity of HAN in combination with cytarabine against human promyelocytic leukemia cells (HL-60 was tested using MTT cell viability assay and trypan blue dye exclusion assay. The combination of cytarabine with HAN showed higher tumor suppression efficiency as compared to that of cytarabine alone. The IC50 values of HAN/cytarabine combination and cytarabine alone were 0.16±0.07 μg/mL and 0.17±0.09 μg/mL, respectively. DNA fragmentation was also studied, and the exposure of HL-60 cells to cytarabine produced 10.70±0.96% DNA fragmentation compared to 18.90±1.33% when cells were exposed to combination of cytarabine with HAN. The antimicrobial activity of hippuric acid and HAN nanocomposite was carried out against Gram-positive bacteria, Gram-negative bacteria, and yeasts. It was found that Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were more sensitive to HAN compared to Bacillus subtilis and Salmonella choleraesuis.

  20. Cytotoxic Effect on Human Myeloma Cells and Leukemic Cells by the Agaricus blazei Murill Based Mushroom Extract, Andosan™

    Directory of Open Access Journals (Sweden)

    Jon-Magnus Tangen

    2017-01-01

    Full Text Available Agaricus blazei Murill is an edible mushroom of the Basidiomycetes family, which has been found to contain a number of compounds with antitumor properties, such as proteoglycans and ergosterol. In the present investigation, we show that the commercial mushroom product Andosan, which contains 82.4% Agaricus blazei Murill, together with medicinal mushrooms Hericium erinaceus (14.7% and Grifola frondosa (2.9%, has a cytotoxic effect on primary myeloma cells, other myeloma cell lines, and leukemia cell lines in vitro. Although the exact content and hence the mechanisms of action of the Andosan extract are unknown, we have found in this investigation indications of cell cycle arrest when myeloma cell lines are cultivated with Andosan. This may be one of the possible explanations for the cytotoxic effects of Andosan.

  1. Cytotoxic Effect on Human Myeloma Cells and Leukemic Cells by the Agaricus blazei Murill Based Mushroom Extract, Andosan™

    Science.gov (United States)

    Holien, Toril; Mirlashari, Mohammad Reza; Misund, Kristine

    2017-01-01

    Agaricus blazei Murill is an edible mushroom of the Basidiomycetes family, which has been found to contain a number of compounds with antitumor properties, such as proteoglycans and ergosterol. In the present investigation, we show that the commercial mushroom product Andosan, which contains 82.4% Agaricus blazei Murill, together with medicinal mushrooms Hericium erinaceus (14.7%) and Grifola frondosa (2.9%), has a cytotoxic effect on primary myeloma cells, other myeloma cell lines, and leukemia cell lines in vitro. Although the exact content and hence the mechanisms of action of the Andosan extract are unknown, we have found in this investigation indications of cell cycle arrest when myeloma cell lines are cultivated with Andosan. This may be one of the possible explanations for the cytotoxic effects of Andosan. PMID:29238712

  2. Intravesical BCG therapy in bladder carcinoma. Effect on cytotoxicity, IL-2 production and phenotype of peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Zeuthen, J

    1991-01-01

    The purpose of the study was to examine the effects of intravesical BCG treatment on the cytotoxicity, interleukin-2 (IL-2) production and distribution of the subsets of peripheral blood mononuclear cells (PBMC) in patients with carcinoma in situ of the bladder. Treatments were made in 6 patients...... during a conventional BCG treatment schedule. Four patients showed a complete response, one a partial response and one had a progressive disease after BCG treatment. Intravesical BCG did not induce significant changes in the cytotoxicity of PBMC. The distribution of NK-cells and T-cells also remained...... unchanged and so did the lectin induced production of IL-2. The results suggest that the effects of intravesical BCG on the immune system should be studied in lymphocytes isolated from the bladder....

  3. Aminosilane Functionalization and Cytotoxicity Effects of Upconversion Nanoparticles YO and GdO Co-Doped with Yband Er

    Directory of Open Access Journals (Sweden)

    Dalia Holanda Chavez

    2016-01-01

    Full Text Available In this study, luminescent upconversion nanoparticles (UCNPs Y 2 O 3 and Gd 2 O 3 co-doped with Yb 3+ and Er 3+ were prepared by the sol-gel method (SG. These NPs are able to absorb near infrared photons and upconvert them into visible radiation with a direct application in bioimaging, as an important tool to diagnose and visualize cancer cells. The UCNPs were coated with a thin silica shell and functionalized with amino groups for further folic acid conjugation to allow their interaction with folate ligands on the cell surface. Their physical properties were analysed by Transmission Electron Microscopy (TEM, Fourier transform infrared spectroscopy (FTIR and photoluminescence (PL measurements. The PL results revealed excellent luminescence properties on all core-shell UCNPs. Cytotoxicity experiments with concentrations of bare and aminosilane coated/functionalized UCNPs between 0.001 μg/mL to 1 μg/mL were tested on two different cell lines from human cervix carcinoma (HeLa and human colorectal adenocarcinoma (DLD-1 with a colorimetric assay based on the reduction of MTT reagent (methy-134-thiazolyltetrazolium. The assays show that some concentrations of bare UCNPs were cytotoxic for cervical adenocarcinoma cells (HeLa; however, for human colorectal adenocarcinoma all UCNPs are non-cytotoxic. After UCNPs functionalization with silica-aminosilane (APTES/TEOS, all of the nanoparticles tested were found to be non-cytotoxic for both cell lines. The UCNPs functionalized in this work can be further conjugated with specific ligands and used as biolabels for detection of cancer cells.

  4. Analysis of cytotoxic effects of chlorhexidine gluconate as antiseptic agent on human blood lymphocytes.

    Science.gov (United States)

    Salimi, Ahmad; Alami, Bahare; Pourahmad, Jalal

    2017-08-01

    The aim of this study was to assess the cytotoxicity of chlorhexidine gluconate (CHG) on human blood lymphocytes as a useful ex vivo model for accelerated human toxicity studies. Using biochemical and flow cytometry assessments, we demonstrated that addition of CHG at 1 μM concentration to human blood lymphocytes induced cytotoxicity following 6 h. The CHG-induced cytotoxicity on human blood lymphocytes was associated with intracellular reactive oxygen species generation, mitochondrial membrane potential collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione. According to our results, CHG triggers oxidative stress and organelles damages in lymphocytes which are important cells in defense against foreign agents. Finally our findings suggest that using of antioxidants and mitochondrial/lysosomal protective agents could be of benefit for the people in the exposure with CHG. © 2017 Wiley Periodicals, Inc.

  5. Biosynthesis, Antimicrobial and Cytotoxic Effect of Silver Nanoparticles Using a Novel Nocardiopsis sp. MBRC-1

    Science.gov (United States)

    Manivasagan, Panchanathan; Senthilkumar, Kalimuthu; Sivakumar, Kannan; Kim, Se-Kwon

    2013-01-01

    The biosynthesis of nanoparticles has been proposed as a cost effective environmental friendly alternative to chemical and physical methods. Microbial synthesis of nanoparticles is under exploration due to wide biomedical applications, research interest in nanotechnology and microbial biotechnology. In the present study, an ecofriendly process for the synthesis of nanoparticles using a novel Nocardiopsis sp. MBRC-1 has been attempted. We used culture supernatant of Nocardiopsis sp. MBRC-1 for the simple and cost effective green synthesis of silver nanoparticles. The reduction of silver ions occurred when silver nitrate solution was treated with the Nocardiopsis sp. MBRC-1 culture supernatant at room temperature. The nanoparticles were characterized by UV-visible, TEM, FE-SEM, EDX, FTIR, and XRD spectroscopy. The nanoparticles exhibited an absorption peak around 420 nm, a characteristic surface plasmon resonance band of silver nanoparticles. They were spherical in shape with an average particle size of 45 ± 0.15 nm. The EDX analysis showed the presence of elemental silver signal in the synthesized nanoparticles. The FTIR analysis revealed that the protein component in the form of enzyme nitrate reductase produced by the isolate in the culture supernatant may be responsible for reduction and as capping agents. The XRD spectrum showed the characteristic Bragg peaks of 1 2 3, 2 0 4, 0 4 3, 1 4 4, and 3 1 1 facets of the face centered cubic silver nanoparticles and confirms that these nanoparticles are crystalline in nature. The prepared silver nanoparticles exhibited strong antimicrobial activity against bacteria and fungi. Cytotoxicity of biosynthesized AgNPs against in vitro human cervical cancer cell line (HeLa) showed a dose-response activity. IC50 value was found to be 200 μg/mL of AgNPs against HeLa cancer cells. Further studies are needed to elucidate the toxicity and the mechanism involved with antimicrobial and anticancer activity of the synthesized Ag

  6. Biosynthesis, antimicrobial and cytotoxic effect of silver nanoparticles using a novel Nocardiopsis sp. MBRC-1.

    Science.gov (United States)

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Senthilkumar, Kalimuthu; Sivakumar, Kannan; Kim, Se-Kwon

    2013-01-01

    The biosynthesis of nanoparticles has been proposed as a cost effective environmental friendly alternative to chemical and physical methods. Microbial synthesis of nanoparticles is under exploration due to wide biomedical applications, research interest in nanotechnology and microbial biotechnology. In the present study, an ecofriendly process for the synthesis of nanoparticles using a novel Nocardiopsis sp. MBRC-1 has been attempted. We used culture supernatant of Nocardiopsis sp. MBRC-1 for the simple and cost effective green synthesis of silver nanoparticles. The reduction of silver ions occurred when silver nitrate solution was treated with the Nocardiopsis sp. MBRC-1 culture supernatant at room temperature. The nanoparticles were characterized by UV-visible, TEM, FE-SEM, EDX, FTIR, and XRD spectroscopy. The nanoparticles exhibited an absorption peak around 420 nm, a characteristic surface plasmon resonance band of silver nanoparticles. They were spherical in shape with an average particle size of 45 ± 0.15 nm. The EDX analysis showed the presence of elemental silver signal in the synthesized nanoparticles. The FTIR analysis revealed that the protein component in the form of enzyme nitrate reductase produced by the isolate in the culture supernatant may be responsible for reduction and as capping agents. The XRD spectrum showed the characteristic Bragg peaks of 1 2 3, 2 0 4, 0 4 3, 1 4 4, and 3 1 1 facets of the face centered cubic silver nanoparticles and confirms that these nanoparticles are crystalline in nature. The prepared silver nanoparticles exhibited strong antimicrobial activity against bacteria and fungi. Cytotoxicity of biosynthesized AgNPs against in vitro human cervical cancer cell line (HeLa) showed a dose-response activity. IC50 value was found to be 200 μg/mL of AgNPs against HeLa cancer cells. Further studies are needed to elucidate the toxicity and the mechanism involved with antimicrobial and anticancer activity of the synthesized AgNPs as

  7. Cytotoxic effects of MGI 114 are independent of tumor p53 or p21 expression.

    Science.gov (United States)

    Izbicka, E; Davidson, K; Lawrence, R; Cote, R; MacDonald, J R; Von Hoff, D D

    1999-01-01

    MGI 114, an analog of illudin S, shows potent activity against a broad range of human tumors in vitro and in vivo, including drug resistant tumors. In this study we examined cytotoxicity of MGI 114 against human tumor cell lines (MCF7, MDA.MB.468, EJ1, J82, SCaBER, KG-1, HL60, and IMR-90) with differing expression of p53 and/or p21 (WAF1) tumor suppressor genes. Only MCF7 and IMR-90 express the wild type p53, WAF1 is present in high levels in MCF7 and SCaBER. WAF1 expression can be induced in KG-1, HL60, and IMR-90. The cells were treated with MGI 114 at 0.1, 1.0 and 10 micrograms/ml in 1 h exposure and with 0.01, 0.1 and 1.0 microgram/ml MGI 114 in a continuous exposure. Cell numbers were measured at days 2, 4, and 7. MGI 114 suppressed growth in all cell lines at day 2 after 1 h exposure at the two highest concentrations and at all concentrations in a continuous exposure. Some cells partly recovered from the inhibition by day 4. Expression of WAF1 had no apparent effect on growth suppression by MGI 114, however, cells with inducible WAF1 showed slower recovery from MGI 114 inhibition in comparison with the cells under non-permissive conditions. Overall, MGI 114 effectively inhibited growth of human cancer cells regardless of their p53 and WAF1 status.

  8. Proinflammatory effects of bacterial lipoprotein on human neutrophil activation status, function and cytotoxic potential in vitro.

    LENUS (Irish Health Repository)

    Power, C

    2012-02-03

    Bacterial lipoprotein (BLP) is the most abundant protein in gram-negative bacterial cell walls, heavily outweighing lipopolysaccharide (LPS). Herein we present findings demonstrating the potent in vitro effects of BLP on neutrophil (PMN) activation status, function, and capacity to transmigrate an endothelial monolayer. PMNs are the principal effectors of the initial host response to injury or infection and constitute a significant threat to invading bacterial pathogens. The systemic inflammatory response syndrome (SIRS) is characterised by significant host tissue injury mediated, in part, by uncontrolled regulation of PMN cytotoxic activity. We found that BLP-activated human PMN as evidenced by increased CD11b\\/CD18 (Mac-1) expression. Up-regulation of PMN Mac-1 in response to BLP occurred independently of membrane-bound CD14 (mCD14). A similar up-regulation of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells was observed whilst E-Selectin expression was unaffected. PMN transmigration across a human umbilical vein endothelial cell (HUVEC) monolayer was markedly increased after treating either PMN\\'s or HUVEC independently with BLP. This increased transmigration did not occur as a result of any direct effect of BLP on HUVEC monolayer permeability, assessed objectively using the passage of FITC-labeled Dextran-70. BLP primed PMN for enhanced respiratory burst and superoxide anion production in response to PMA, but did not influence phagocytosis of opsonized Escherichia coli. BLP far exceeds LPS as a gram-negative bacterial wall component, these findings therefore implicate BLP as an additional putative mediator of SIRS arising from gram-negative infection.

  9. Shape Effect on Particle-Lipid Bilayer Membrane Association, Cellular Uptake, and Cytotoxicity.

    Science.gov (United States)

    Tree-Udom, Thapakorn; Seemork, Jiraporn; Shigyou, Kazuki; Hamada, Tsutomu; Sangphech, Naunpun; Palaga, Tanapat; Insin, Numpon; Pan-In, Porntip; Wanichwecharungruang, Supason

    2015-11-04

    Although computer simulation and cell culture experiments have shown that elongated spherical particles can be taken up into cells more efficiently than spherical particles, experimental investigation on effects of these different shapes over the particle-membrane association has never been reported. Therefore, whether the higher cellular uptake of an elongated spherical particles is a result of a better particle-membrane association as suggested by some calculation works or a consequence of its influence on other cellular trans-membrane components involved in particle translocation process, cannot be concluded. Here, we study the effect of particle shape on the particle-membrane interaction by monitoring the association between particles of various shapes and lipid bilayer membrane of artificial cell-sized liposomes. Among the three shaped lanthanide-doped NaYF4 particles, all with high shape purity and uniformity, similar crystal phase, and surface chemistry, the elongated spherical particle shows the highest level of membrane association, followed by the spherical particle with a similar radius, and the hexagonal prism-shaped particle, respectively. The free energy of membrane curvature calculated based on a membrane indentation induced by a particle association indicates that among the three particle shapes, the elongated spherical particle give the most stable membrane curvature. The elongated spherical particles show the highest cellular uptake into cytosol of human melanoma (A-375) and human liver carcinoma (HepG2) cells when observed through a confocal laser scanning fluorescence microscope. Quantitative study using flow cytometry also gives the same result. The elongated spherical particles also possess the highest cytotoxicity in A-375 and normal skin (WI-38) cell lines, comparing to the other two shaped particles.

  10. Cytotoxic effects of thiamethoxam in the midgut and malpighian tubules of Africanized Apis mellifera (Hymenoptera: Apidae).

    Science.gov (United States)

    Catae, Aline Fernanda; Roat, Thaisa Cristina; De Oliveira, Regiane Alves; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar

    2014-04-01

    Due to its expansion, agriculture has become increasingly dependent on the use of pesticides. However, the indiscriminate use of insecticides has had additional effects on the environment. These products have a broad spectrum of action, and therefore the insecticide affects not only the pests but also non-target insects such as bees, which are important pollinators of agricultural crops and natural environments. Among the most used pesticides, the neonicotinoids are particularly harmful. One of the neonicotinoids of specific concern is thiamethoxam, which is used on a wide variety of crops and is toxic to bees. Thus, this study aimed to analyze the effects of this insecticide in the midgut and Malpighian tubule cells of Africanized Apis mellifera. Newly emerged workers were exposed until 8 days to a diet containing a sublethal dose of thiamethoxam equal to 1/10 of LC₅₀ (0.0428 ng a.i./l L of diet). The bees were dissected and the organs were processed for transmission electron microscopy. The results showed that thiamethoxam is cytotoxic to midgut and Malpighian tubules. In the midgut, the damage was more evident in bees exposed to the insecticide on the first day. On the eighth day, the cells were ultrastructurally intact suggesting a recovery of this organ. The Malpighian tubules showed pronounced alterations on the eighth day of exposure of bees to the insecticide. This study demonstrates that the continuous exposure to a sublethal dose of thiamethoxam can impair organs that are used during the metabolism of the insecticide. Copyright © 2014 Wiley Periodicals, Inc.

  11. Bactericidal and cytotoxic effects of chloramine-T on wound pathogens and human fibroblasts in vitro.

    Science.gov (United States)

    Kloth, Luther C; Berman, Joseph E; Laatsch, Linda J; Kirchner, Phyllis A

    2007-06-01

    To evaluate cytotoxicity and bactericidal effects of chloramine-T. In vitro study of various concentrations and exposure times to preparations containing human fibroblasts or 1.5 x 10 colony forming units per milliliter (CFU/mL) of 3 gram-positive bacteria-Staphylococcus aureus, methicillin-resistant S aureus, and vancomycin-resistant Enterococcus faecalis-and 2 gram-negative bacteria-Escherichia coli and Pseudomonas aeruginosa-with and without fetal bovine serum present. Percentage reduction of bacterial growth and percentage of viable fibroblasts 48 hours after exposure. All gram-positive growth was reduced by 95% to 100%, regardless of dose, with or without serum. E coli (gram-negative; with/without serum) was reduced 94% to 100% at antiseptic concentrations of 300 and 400 ppm. At 200 ppm, E coli growth was fully inhibited without serum present and by 50% with serum. P aeruginosa (gram-negative) was not significantly affected under any conditions. At 100 and 200 ppm, cell viability remained greater than 90% under all experimental conditions. A 300-ppm, 3-minute exposure to chloramine-T resulted in cell viability of up to 70%, with longer exposures producing lower viabilities. Serum did not affect cell viability in any condition. In vitro, chloramine-T at 200 ppm for 5 to 20 minutes was effective against 3 virulent gram-positive bacteria without fibroblast damage. At 300 ppm and 3 and 5 minutes, 30% of fibroblasts were damaged and 95% to 100 % of E coli were inhibited, respectively.

  12. Novel siRNA delivery system using a ternary polymer complex with strong silencing effect and no cytotoxicity.

    Science.gov (United States)

    Kodama, Yukinobu; Shiokawa, Yumi; Nakamura, Tadahiro; Kurosaki, Tomoaki; Aki, Keisei; Nakagawa, Hiroo; Muro, Takahiro; Kitahara, Takashi; Higuchi, Norihide; Sasaki, Hitoshi

    2014-01-01

    We developed a novel small interfering RNA (siRNA) delivery system using a ternary complex with polyethyleneimine (PEI) and γ-polyglutamic acid (γ-PGA), which showed silencing effect and no cytotoxicity. The binary complexes of siRNA with PEI were approximately 73-102 nm in particle size and 45-52 mV in ζ-potential. The silencing effect of siRNA/PEI complexes increased with an increase of PEI, and siRNA/PEI complexes with a charge ratio greater than 16 showed significant luciferase knockdown in a mouse colon carcinoma cell line regularly expressing luciferase (Colon26/Luc cells). However, strong cytotoxicity and blood agglutination were observed in the siRNA/Lipofectamine complex and siRNA/PEI16 complex. Recharging cationic complexes with an anionic compound was reported to be a promising method for overcoming these toxicities. We therefore prepared ternary complexes of siRNA with PEI (charge ratio 16) by the addition of γ-PGA to reduce cytotoxicity and deliver siRNA. As expected, the cytotoxicity of the ternary complexes decreased with an increase of γ-PGA content, which decreased the ζ-potential of the complexes. A strong silencing effect comparable to siRNA/Lipofectamine complex was discovered in ternary complexes including γ-PGA with an anionic surface charge. The high incorporation of ternary complexes into Colon26/Luc cells was confirmed with fluorescence microcopy. Having achieved knockdown of an exogenously transfected gene, the ability of the complex to mediate knockdown of an endogenous housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), was assessed in B16-F10 cells. The ternary complex (siRNA/PEI16/γ-PGA12 complex) exhibited a significant GAPDH knockdown effect. Thus, we developed a useful siRNA delivery system.

  13. Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215

    OpenAIRE

    Szereday, Z; Schally, A V; Nagy, A; Plonowski, A; Bajo, A M; Halmos, G; Szepeshazi, K; Groot, K

    2002-01-01

    Some brain tumours, such as glioblastomas express high levels of receptors for bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carrier. This study reports the effect of AN-215 on the growth of U-87MG human glioblastomas...

  14. Evaluation of chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effects of Aloysia citrodora extract on colon cancer cell line

    OpenAIRE

    Amir Mirzaie; Seyed Ataollah Sadat Shandiz; Hassan Noorbazargan; Elahe Ali Asgary

    2016-01-01

    Background: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer (HT29) cells by using real-time polymerase chain reaction and flow-cytometry methods. Methods: This experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to...

  15. Effects of total flavonoids of sea buckthorn ( Hippophae rhamnoides L.) on cytotoxicity of NK92-MI cells.

    Science.gov (United States)

    Hou, Diandong; Wang, Decheng; Ma, Xiande; Chen, Wenna; Guo, Shengnan; Guan, Hongquan

    2017-12-01

    Sea buckthorn ( Hippophae rhamnoides L.) has multifarious medicinal properties including immunoregulatory effect. The total flavonoids of Hippophae rhamnoides L. (TFH) are the main active components isolated from berries of sea buckthorn. The aim of this study was to evaluate the effects of TFH on the cytotoxicity of NK92-MI cells and its possible mechanisms. NK92-MI cells were treated with TFH (2.5 or 5.0 mg/L) or phosphate-buffered saline (PBS) for 24 h, the cytotoxicity against K562 was detected by measuring the release of lactate dehydrogenase (LDH), expression levels of NCRs (NKp30, NKp44, NKp46) and NKG2D were detected by flow cytometry, and expression levels of perforin and granzyme B were detected by western blot. Cytokine Antibody Arrays with 80 cytokine proteins were used to profile the effect of TFH on cytokines. Western blot was adopted to detect the effects of TFH on STAT1, STAT4, and STAT5 signal pathway. Compared with the normal control group, TFH could significantly enhance NK92-MI cell cytotoxicity against K562 cells, upregulate expressions of NKp44, NKp46, perforin, and granzyme B. TFH could upregulate expressions of IL-1α, IL-2, IL-7, IL-15, CSF-2, CSF-3, MCP-1, MIG, IFN-γ, TNF-α, and TNF-β and downregulate expressions of IL-16, MIP-1β, CX3CL-1, and MIF. TFH could increase expressions of phospho-STAT1 and phospho-STAT5. The results suggest that TFH stimulated NK92-MI cells to activate and enhance cytotoxicity of NK92-MI cells.

  16. Effects of stresses on the growth and Cytotoxicity of Shiga-Toxin producing Escherichia coli in ground beef and spinach

    Science.gov (United States)

    The objectives of this study were to examine the effect of stresses on the growth and cytotoxicity of pathogenic Escherichia coli in beef and spinach. A mixture of three strains of Shiga toxin-producing E. coli (STEC) O157:H7 or four strains of non-O157 STEC O26:H11, O103:H1, O104:H4, and O145:NM wa...

  17. Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro

    OpenAIRE

    Weissenstein, Ulrike; Kunz, Matthias; Urech, Konrad; Baumgartner, Stephan

    2014-01-01

    Background Given the importance of complementary and alternative medicine (CAM) to cancer patients, there is an increasing need to learn more about possible interactions between CAM and anticancer drugs. Mistletoe (Viscum album L.) belongs to the medicinal herbs that are used as supportive care during chemotherapy. In the in vitro study presented here the effect of standardized mistletoe preparations on the cytostatic and cytotoxic activity of several common conventional chemotherapeutic drug...

  18. Effect of exposure time, particle size and uptake pathways in immune cell lysosomal cytotoxicity of mussels exposed to silver nanoparticles.

    Science.gov (United States)

    Bouallegui, Younes; Ben Younes, Ridha; Turki, Faten; Mezni, Amine; Oueslati, Ridha

    2018-04-01

    Cytotoxicity evaluation of hemocytes (lysosomal membrane stability [LMS] assay) from Mytilus galloprovincialis Lamarck, exposed to a sublethal dose (100 μg/L) of two size of silver nanoparticles (AgNPs: <50 nm and <100 nm) - prior to and after inhibition of potential uptake pathways (i.e., clathrin- and caveolae-mediated endocytosis) within different times of exposure (3, 6, 12 h) - showed that there was a significant cytotoxic effect on immune cells of mussels exposed for different times to either AgNP size (p < 0.01); the greater effect was with the smaller size. However, hemocytes seemed more sensitive to the larger AgNP after clathrin-mediated endocytosis was blocked (p < 0.01); this was not so with inhibition of caveolae-mediated endocytosis. Dimethyl-sulfoxide (DMSO) did not impart a carrier-mediated effect despite an enhanced cytotoxicity when DMSO was present with AgNP. From these results, it is concluded that the immunotoxicity of AgNP in mussels was size-dependent as well as length of exposure-dependent. It was also clear that nanoparticles (NP) internalization mechanisms were a major factor underlying any toxicity.

  19. Cytotoxic effect of zinc oxide nanoparticles on murine photoreceptor cells via potassium channel block and Na(+) /K(+) -ATPase inhibition.

    Science.gov (United States)

    Chen, Chao; Bu, Wenjuan; Ding, Hongyan; Li, Qin; Wang, Dabo; Bi, Hongsheng; Guo, Dadong

    2017-06-01

    Zinc oxide (ZnO) nanoparticles can exhibit toxicity towards organisms and oxidative stress is often hypothesized to be one of the most important factors. Nevertheless, the detailed mechanism of toxicity-induced by ZnO nanoparticles has not been completely addressed. The present study aimed to investigate the toxic effects of ZnO nanoparticles on the expression and activity of Na(+) /K(+) -ATPase and on potassium channel block. In the present study, we explored the cytotoxic effect of ZnO nanoparticles on murine photoreceptor cells using lactate dehydrogenase (LDH) release assay, reactive oxygen species (ROS) determination, mitochondrial membrane potential (Δφm) measurement, delayed rectifier potassium current recordings and Na(+) /K(+) -ATPase expression and activity monitoring. The results indicated that ZnO nanoparticles could increase the LDH release in medium, aggravate the ROS level within cells, collapse the Δφm, block the delayed rectifier potassium current, and attenuate the expressions of Na(+) /K(+) -ATPase at both mRNA and protein levels and its activity, and thus exert cytotoxic effects on murine photoreceptor cells, finally damaging target cells. Our findings will facilitate the understanding of the mechanism involved in ZnO nanoparticle-induced cytotoxicity in murine photoreceptor cells via potassium channel block and Na(+) /K(+) -ATPase inhibition. © 2017 John Wiley & Sons Ltd.

  20. Assessment of cytotoxic and cytogenetic effects of a 1,2,5-thiadiazole derivative on CHO-K1 cells. Its application as corrosion inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Grillo, C.A. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA, CCT La Plata-CONICET), Facultad de Ciencias Exactas, Departamento de Quimica, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, 1900 La Plata (Argentina); Mirifico, M.V. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA, CCT La Plata-CONICET), Facultad de Ciencias Exactas, Departamento de Quimica, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, 1900 La Plata (Argentina); Facultad de Ingenieria, Areas Departamentales Ingenieria Quimica and Mecanica, Universidad Nacional de La Plata, Calle 47 y 1, 1900 La Plata (Argentina); Morales, M.L. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA, CCT La Plata-CONICET), Facultad de Ciencias Exactas, Departamento de Quimica, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, 1900 La Plata (Argentina); Reigosa, M.A. [IMBICE (Instituto Multidisciplinario de Biologia Celular), CICPBA, CONICET, Calle 526 entre 10 y 11, 1900 La Plata (Argentina); Mele, M. Fernandez Lorenzo de, E-mail: mmele@inifta.unlp.edu.ar [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA, CCT La Plata-CONICET), Facultad de Ciencias Exactas, Departamento de Quimica, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4, 1900 La Plata (Argentina); Facultad de Ingenieria, Areas Departamentales Ingenieria Quimica and Mecanica, Universidad Nacional de La Plata, Calle 47 y 1, 1900 La Plata (Argentina)

    2009-10-30

    This work focuses on the possible use of phenanthro[9,10-c]-1,2,5-thiadiazole 1,1-dioxide (TDZ) as a harmless corrosion inhibitor. TDZ range-dose providing minimum adverse effects to the environment and human health, with satisfactory corrosion-inhibiting properties was evaluated. Cytotoxicity and genotoxicity of TDZ at 0.57-12.50 {mu}M concentration range were tested by neutral red, chromosomal aberrations, mitotic index, and colony formation assays. Results showed a significant increase of chromatid-type aberrations for the highest concentration of TDZ assayed (12.50 {mu}M). Additionally, a reduction in the proliferative rate for lower concentrations was detected by the MI assay. We concluded that TDZ should be used at concentrations lower than 1.16 {mu}M. Corrosion assays performed showed good inhibition effect (ca. 50%) at low (0.65 {mu}M) TDZ concentration. Consequently, our results indicated that TDZ induced a time- and dose-dependent genotoxic and cytotoxic response on CHO-K1 cells. Short assays should be complemented with long exposure tests to simulate chronic contact with TDZ since lower threshold levels may be found for shorter exposures and a wrong safety range could be determined.

  1. Functional characteristics, wettability properties and cytotoxic effect of starch film incorporated with multi-walled and hydroxylated multi-walled carbon nanotubes.

    Science.gov (United States)

    Shahbazi, Mahdiyar; Rajabzadeh, Ghadir; Sotoodeh, Shahnaz

    2017-11-01

    Two types of multi-walled carbon nanotubes (CNT and CNT-OH) at different levels (0.1-0.9wt%) were introduced into starch matrix in order to modify its functional properties. The optimum concentration of each nanotube was selected based on the results of water solubility, water permeability and mechanical experiments. The physico-mechanical data showed that CNT up to 0.7wt% led to a notable increase in water resistance, water barrier property and tensile strength, whilst regarding CNT-OH, these improvements found at 0.9wt%. Therefore, effects of optimized level of each nanotube on the starch film were evaluated by XRD, surface hydrophobicity, wettability and surface energy tests. XRD revealed that the position of starch characteristic peak shifted to higher degree after nanotubes introducing. The hydrophobic character of the film was greatly increased with incorporation of nanoparticles, as evidenced by increased contact angle with greatest value regarding CNT-OH. Moreover, CNT-OH notably decreased the surface free energy of the starch film. Finally, the conformity of both nanocomposites with actual food regulations on biodegradable materials was tested by cytotoxicity assay to evaluate the possibility of application in food packaging sector. Both nanocomposite films had potential of cytotoxic effects, since they could increase cytoplasmic lactate dehydrogenase release from L-929 fibroblast cells in contact with their surface. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. In vitro effect of low intensity laser on the cytotoxicity produced by substances released by bleaching gel

    Directory of Open Access Journals (Sweden)

    Caroline Maria Gomes Dantas

    2010-12-01

    Full Text Available This in vitro study aimed to analyze the effect of different parameters of phototherapy with low intensity laser on the viability of human dental pulp fibroblasts under the effect of substances released by bleaching gel. Cells were seeded into 96 wells plates (1 x 10³ cells/well and placed in contact with culture medium conditioned by a 35 % hydrogen peroxide bleaching gel for 40 minutes, simulating the clinical condition of the in-office bleaching treatment. Cells cultured in ideal growth conditions served as positive control group (PC, and the cells grown in conditioned medium and non-irradiated served as negative control group (NC. Cells grown in conditioned medium were submitted to a single irradiation with a diode laser (40 mW, 0.04 cm² emitting at visible red (660 nm; RL or near infrared (780 nm; NIR using punctual technique, in contact mode and energy densities of 4, 6 or 10 J/cm². The cell viability was analyzed through the MTT reduction assay immediately and 24 hours after the irradiation. The data was compared by ANOVA followed by the Tukey's test (p < 0.05. The cell viability increased significantly in 24 hours within each group. The PC presented cell viability significantly higher than NC in both experimental times. Only the NIR/10 J/cm² group presented cell viability similar to that of PC in 24 hours. The phototherapy with low intensity laser in defined parameters is able to compensate the cytotoxic effects of substances released by 35 % hydrogen peroxide bleaching gel.

  3. Genotoxic and cytotoxic effects of X-ray on buccal epithelial cells following panoramic radiography: A pediatric study

    Directory of Open Access Journals (Sweden)

    Poonam Agarwal

    2015-01-01

    Full Text Available Background: Ionizing radiation is a potent mutagenic agent capable of inducing both mutation and chromosomal aberrations. Non-lethal doses of ionizing radiation may induce genomic instability favoring carcinogenesis. In spite of their mutagenic potential, this kind of radiation is an important tool for diagnosis of the disease and is used in medical and dental practice. It has been believed that the number of micronucleus and increased frequency of other nuclear alterations, including karyorrhexis, condensed chromatin and pyknosis, are related to the increasing effects of carcinogens. Many approaches and techniques have been developed for the monitoring of human populations exposed to various mutagens, but the analysis of micronuclei (MN has become a standard approach for the assessment of chromosomal damage in human populations. Aim: To assess the effects of radiation exposure from panoramic radiography on the buccal epithelial cells (BECs of pediatric patients. Materials and Methods: The study included 20 pediatric patients who had to undergo panoramic radiography for further dental treatment. Exfoliated BECs were obtained and examined immediately before and 10 days after radiation exposure. The cells were stained using rapid Papanicolaou (PAP kit. Evaluation for MN and nuclear alterations was carried out by an oral pathologist and data were statistically analyzed using the "t" test. Results: The mean number of MN in the BECs before exposure of pediatric patients to panoramic radiography was 4.25 and after exposure was 4.40. This difference was not found to be statistically significant (P < 0.0001. However, the mean nuclear alterations of 8.70 and 15.75 before and after exposure were statistically significant (P < 0.0001. Conclusion: Panoramic radiographs can induce cytotoxicity but not genotoxic effects in buccal mucosal cells. Hence, dental radiographs should be prescribed only when deemed indispensable.

  4. Cytotoxic effects of polyhexanide on cellular repopulation and calcification of decellularized equine carotids in vitro and in vivo.

    Science.gov (United States)

    Böer, Ulrike; Spengler, Claas; Klingenberg, Melanie; Jonigk, Danny; Harder, Michael; Kreipe, Hans-Heinrich; Haverich, Axel; Wilhelmi, Mathias

    2013-03-01

    Disinfection of biological implants is indispensable for clinical safety. Here, decellularized equine carotid arteries (dECAs) were disinfected by polyhexanide (PHX), an effective, well-tolerated and nontoxic wound disinfectant and evaluated as vascular grafts for their repopulation and local biocompatibility in vivo. 
 dECAs were terminally disinfected by a combination of 0.1% PHX and 70% ethanol (dECA_PHX-ET) or exclusively ethanol (dECA-ET) and subsequently implanted as arteriovenous shunts in sheep for 14 weeks. Repopulation was determined by immunohistochemistry for endothelial- (ECs) or smooth muscle cells (SMCs) using antibodies against CD31 and smooth muscle actin. Histological evaluation was performed on HE-stained sections. Cytotoxicity of dECAs was measured directly by seeding the scaffolds with L-929 fibroblasts, which were visualized by calcein staining. Indirect cytotoxicity was determined by WST-8 viability assay by incubation of L-929 with dECA extracts. 
 dECA_PHX-ET completely lacked repopulation with ECs and SMCs, showed leukocyte infiltration, strong calcification and poor neovascularization indicating insufficient biocompatibility and inflammatory graft degeneration. PHX-treatment reduced cell viability to 33.2 ± 12.6% and disturbed cell growth at direct contact. In contrast, dECA_ET had no direct cytotoxic effect and only slightly influenced cell viability (82.9 ± 12.5%), showed a substantial repopulation by ECs and SMCs including neovascularization, and were only slightly calcified. 
 The disinfectant polyhexanide seems to exert severe cytotoxic effects when used for the processing of decellularized matrices and may result in degenerative graft deterioration. In contrast, dECAs exclusively disinfected with ethanol were well integrated. Thus, ethanol seems to be a more suitable tool for graft processing than polyhexanide.

  5. Cytotoxic Activities of Phytochemicals from Ferula Species

    Directory of Open Access Journals (Sweden)

    Seied Mojtaba Valiahdi

    2013-05-01

    Full Text Available Background:Ferula species are reputed in folk medicine for the treatment of a variety of disorders. There have been sporadic reports on the chemopreventive and chemosensitizing activities of some terpenoid coumarin derivatives from the genus Ferula. The present study investigated the cytotoxic activity of 11 phytochemicals (conferone, farnesiferol A, acantrifoside E, mogoltadone, diversin, galbanic acid, herniarin, 7-isopentenyloxycoumarin, umbelliprenin, stylosin and tschimgine from Ferula species together with a newly synthesized prenylated derivative of curcumin (gercumin II.Methods:Cytotoxic activity of phytochemicals was evaluated against ovarian carcinoma (CH1, lung cancer (A549 and melanoma (SK-MEL-28 cell lines using MTT assay.Results and conclusion:Overall, moderate cytotoxic activity was observed from the tested compounds with IC50 values in the micromolar range. The highest activity against CH1 and A549 lines was from conferone while stylosin and tschimgine were the most potent compounds against SK-MEL-28 line. In conclusion, the findings of the present investigation did not support a potent cytotoxic activity of the tested phytochemicals against CH1, A549 and SK-MEL-28 cell lines. With respect to previous reports, the beneficial impact of these phytochemicals in cancer therapy may be more attributable to their chemopreventive or chemosensitizing activity rather than direct cytotoxic effects.

  6. Investigation of Astragalus honey and propolis extract's cytotoxic effect on two human cancer cell lines and their oncogen and proapoptotic gene expression profiles.

    Science.gov (United States)

    Sadeghi-Aliabadi, Hojjat; Hamzeh, Jamal; Mirian, Mina

    2015-01-01

    Cancer is one of the major fatal human diseases. Natural products have been used in the treatment of cancer for long time. Bee products including honey and propolis have been introduced for malignancy treatment in recent decades. In this study cytotoxicity of bee products and their effects on the expression of proapoptotic genes have been investigated. Cytotoxic effects of Astragalus honey, ethanol extract of propolis and a sugar solution (as control) against HepG2, 5637 and L929 cell lines have been evaluated by the MTT assay. Total RNAs of treated cells were isolated and p53 and Bcl-2 gene expression were evaluated, using real-time PCR. Propolis IC50 values were 58, 30 and 15 μg/ml against L929, HepG2 and 5637, respectively. These values for honey were 3.1%, 2.4% and 1.9%, respectively. Propolis extract has increased the expression of the Bcl-2 gene in all cell lines whereas the honey decreased that significantly (P honey and propolis decreased p53 gene expression in HepG2 and 5637 significantly but not in L929 cells. The sugar solution increased the expression of p53 in two cancer cell lines but no significant changes were observed in the expression of this gene in L929 as normal mouse cell. By downregulation of Bcl-2 expression it could be concluded that the cytotoxicity of honey was more than two fold against tested cancer cells compared with the sugar solution. No significant changes were observed in the expression of p53 in honey-treated cells. Propolis had no significant effect on Bcl-2 and p53 gene expressions (P > 0.05).

  7. Effect of processing, post-harvest irradiation, and production system on the cytotoxicity and mutagenicity of Vitis labrusca L. juices in HTC cells.

    Science.gov (United States)

    Düsman, Elisângela; de Almeida, Igor Vivian; Lucchetta, Luciano; Vicentini, Veronica Elisa Pimenta

    2014-01-01

    The juices of grapes (Vitis labrusca L.) are similar to the fruit itself because the main constituents of the fruit are present in the juice. However, their quality characteristics may be modified by the harsh technological processes used for the production of integral food, such as production systems of raw materials and post-harvest treatment of grapes with ultraviolet (UV) irradiation. Therefore, the present study analyzed juices produced naturally (by liquefying the fruit) or by the technological process of extraction by steam distillation (90°C) of grapes from organic and conventional production systems that were untreated or treated with UV type C (65.6 J/m² for 10 minutes). Using cultures of Rattus norvegicus hepatoma cells (HTC) in vitro, cytotoxic effects were assayed by the MTT test and by calculating the cytokinesis blocked proliferation index (CBPI), and mutagenic effects were measured by the cytokinesis block micronucleus assay. The results of the MTT assay and the CBPIs indicated that none of the juices were cytotoxic, including those that induced cell proliferation. The results of the micronucleus assay showed that none of the juices were mutagenic. However, the average number of micronuclei was lower in the juices produced from organic grapes, and cell proliferation, soluble acids and phenolic compounds were significantly higher. Compared with the natural juices, the integral juices of conventional grapes showed a higher average number of micronuclei as well as lower stimulation of cell proliferation and lower levels of bioactive compounds. The results demonstrate a beneficial effect of UV-C irradiation of post-harvest grapes in stimulating the synthesis of nutraceutical compounds without generating cytotoxic or mutagenic substances. Taken together, our findings support the consumption of grape juice and the application of food production techniques that enhance its nutritional value and promote its production, marketing and consumption.

  8. Effect of processing, post-harvest irradiation, and production system on the cytotoxicity and mutagenicity of Vitis labrusca L. juices in HTC cells.

    Directory of Open Access Journals (Sweden)

    Elisângela Düsman

    Full Text Available The juices of grapes (Vitis labrusca L. are similar to the fruit itself because the main constituents of the fruit are present in the juice. However, their quality characteristics may be modified by the harsh technological processes used for the production of integral food, such as production systems of raw materials and post-harvest treatment of grapes with ultraviolet (UV irradiation. Therefore, the present study analyzed juices produced naturally (by liquefying the fruit or by the technological process of extraction by steam distillation (90°C of grapes from organic and conventional production systems that were untreated or treated with UV type C (65.6 J/m² for 10 minutes. Using cultures of Rattus norvegicus hepatoma cells (HTC in vitro, cytotoxic effects were assayed by the MTT test and by calculating the cytokinesis blocked proliferation index (CBPI, and mutagenic effects were measured by the cytokinesis block micronucleus assay. The results of the MTT assay and the CBPIs indicated that none of the juices were cytotoxic, including those that induced cell proliferation. The results of the micronucleus assay showed that none of the juices were mutagenic. However, the average number of micronuclei was lower in the juices produced from organic grapes, and cell proliferation, soluble acids and phenolic compounds were significantly higher. Compared with the natural juices, the integral juices of conventional grapes showed a higher average number of micronuclei as well as lower stimulation of cell proliferation and lower levels of bioactive compounds. The results demonstrate a beneficial effect of UV-C irradiation of post-harvest grapes in stimulating the synthesis of nutraceutical compounds without generating cytotoxic or mutagenic substances. Taken together, our findings support the consumption of grape juice and the application of food production techniques that enhance its nutritional value and promote its production, marketing and

  9. Cytotoxic effects of one-step self-etching adhesives on an odontoblast cell line.

    Science.gov (United States)

    Lee, Yoon; An, So-Youn; Park, Yoon-Jung; Yu, Frank H; Park, Joo-Cheol; Seo, Deog-Gyu

    2016-01-01

    The aim of this study was to evaluate the cytotoxic effects of one-step self-etching adhesives. Cells from an immortalized mouse odontoblast cell line (MDPC-23) were cultured with six different dental adhesive systems (diluted to concentrations of 0.5% for 4 h): Adper Easy Bond (EB), Xeno V (XV), iBond (IB), AdheSE One (AO), Clearfil SE primer (CS), and Adper Single Bond 2 (SB). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometric apoptosis assays were used to evaluate cell viability and the rate of apoptosis. The odontoblasts were also examined under a scanning electron microscope. While all of the cultures with adhesives showed reduced viability, the viabilities in the IB and SB groups were not significantly different from the control group. Although increased apoptosis rates were observed in all of the cultures with adhesives, the rate in the SB group was not significantly different from the rate in the control. The control group showed the lowest apoptosis rate followed by the SB, AO, IB, EB, XV, and CS groups. When examined under a scanning electron microscope, control odontoblasts and the SB group exhibited relatively large cytoplasmic extensions. In contrast, in the EB and CS groups, fewer fibroblasts remained adhered to the plate surface. Cytoplasmic membrane shrinkage and cell-free areas with residual membrane fragments from dead cells were observed. In conclusion, all cultures with one-step self-etching adhesives showed increased apoptotic activity. SB, an etch-and-rinse adhesive, was comparable to the control group, and CS and EB showed the lowest odontoblast viabilities according to the MTT assay. © Wiley Periodicals, Inc.

  10. Assessment of Radiation Induced Therapeutic Effect and Cytotoxicity in Cancer Patients Based on Transcriptomic Profiling

    Directory of Open Access Journals (Sweden)

    Sajjad Karim

    2016-02-01

    Full Text Available Toxicity induced by radiation therapy is a curse for cancer patients undergoing treatment. It is imperative to understand and define an ideal condition where the positive effects notably outweigh the negative. We used a microarray meta-analysis approach to measure global gene-expression before and after radiation exposure. Bioinformatic tools were used for pathways, network, gene ontology and toxicity related studies. We found 429 differentially expressed genes at fold change >2 and p-value <0.05. The most significantly upregulated genes were synuclein alpha (SNCA, carbonic anhydrase I (CA1, X-linked Kx blood group (XK, glycophorin A and B (GYPA and GYPB, and hemogen (HEMGN, while downregulated ones were membrane-spanning 4-domains, subfamily A member 1 (MS4A1, immunoglobulin heavy constant mu (IGHM, chemokine (C-C motif receptor 7 (CCR7, BTB and CNC homology 1 transcription factor 2 (BACH2, and B-cell CLL/lymphoma 11B (BCL11B. Pathway analysis revealed calcium-induced T lymphocyte apoptosis and the role of nuclear factor of activated T-cells (NFAT in regulation of the immune response as the most inhibited pathways, while apoptosis signaling was significantly activated. Most of the normal biofunctions were significantly decreased while cell death and survival process were activated. Gene ontology enrichment analysis revealed the immune system process as the most overrepresented group under the biological process category. Toxicity function analysis identified liver, kidney and heart to be the most affected organs during and after radiation therapy. The identified biomarkers and alterations in molecular pathways induced by radiation therapy should be further investigated to reduce the cytotoxicity and development of fatigue.

  11. Ankaflavin from Monascus-fermented red rice exhibits selective cytotoxic effect and induces cell death on Hep G2 cells.

    Science.gov (United States)

    Su, Nan-Wei; Lin, Yii-Lih; Lee, Min-Hsiung; Ho, Chen-Ying

    2005-03-23

    Monascus-fermented red rice has traditionally been used as a natural food colorant or food preservative of meat and fish for centuries. Recently, it has become a popular dietary supplement due to many of its bioactive constituents being discovered. Commercial Monascus-fermented red rice was used in this study. According to the cell-based cytotoxicity assay, a compound with selective cytotoxicity was found and identified as ankaflavin. Ankaflavin was found to be toxic to human cancer cell lines Hep G2 and A549 with a similar IC50 value of 15 microg/mL, while it posed no significant toxicity to normal MRC-5 and WI-38 cells at the same concentration. For elucidating the possible mode of cell death, Hep G2 cells were treated with ankaflavin for 48 h to examine the morphological change of the chromatin. Chromosomal condensation and fragmentation were found, and a significant sub-G1 peak was found by flow cytometry. Apoptosis was therefore suggested as the possible mechanism. Monascin, an analogue of ankaflavin, was also tested in this study. However, it showed no cytotoxicity and did not induce death of Hep G2 cells.

  12. Safety and effectiveness of scalp cooling in cancer patients undergoing cytotoxic treatment

    NARCIS (Netherlands)

    Hurk, Corina Johanna Geertruida van den

    2013-01-01

    Various cytotoxics cause severe alopecia, it is estimated to affect more than 15.000 Dutch cancer patients per year. Hair loss has high impact on the majority of these patients, they describe it as stigmatizing and a constant reminder of cancer disease. Scalp cooling decreases hair loss and is well

  13. Effects of serum albumin on the degradation and cytotoxicity of single-walled carbon nanotubes.

    Science.gov (United States)

    Ding, Yun; Tian, Rong; Yang, Zhen; Chen, Jianfa; Lu, Naihao

    2017-03-01

    Neutrophil myeloperoxidase (MPO) and peroxynitrite (ONOO-) can oxidatively biodegrade carboxylated single-walled carbon nanotubes (SWCNTs). The protein-SWCNTs interactions will play an important role in the degradation and cytotoxicity of nanotubes. Here, we investigated the binding of bovine serum albumin (BSA, a common and well-characterized model blood serum protein) to SWCNTs, and found that the hydrophobic and electrostatic interactions might be crucial factors in stabilizing the binding of SWCNTs with BSA. The binding of BSA could impair SWCNTs biodegradation in vitro through the competitive adsorption to nanotube. Both SWCNTs and BSA-SWCNTs were significantly degraded in zymosan-stimulated macrophages, and the degradation degree was more for BSA-SWCNTs. The mechanism for SWCNTs degradation in activated macrophages was further investigated to demonstrate the dominant participation of MPO and ONOO--driven pathways. Moreover, binding of BSA to SWCNTs reduced cytotoxicity and degraded nanotubes induced less cytotoxicity than non-degraded nanotubes. The binding of BSA may be an important determinant for the biodegradation and cytotoxicity of SWCNTs in inflammatory cells, and therefore, provide a new route to mitigate the potential toxicity of nanotubes in future biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Natural chlorophyll but not chlorophyllin prevents heme-induced cytotoxic and hyperproliferative effects in rat colon

    NARCIS (Netherlands)

    Vogel, de J.; Jonker-Termont, D.S.M.L.; Katan, M.B.; Meer, van der R.

    2005-01-01

    Diets high in red meat and low in green vegetables are associated with an increased risk of colon cancer. In rats, dietary heme, mimicking red meat, increases colonic cytotoxicity and proliferation of the colonocytes, whereas addition of chlorophyll from green vegetables inhibits these heme-induced

  15. Cell Proliferation and Cytotoxicity Assays.

    Science.gov (United States)

    Adan, Aysun; Kiraz, Yağmur; Baran, Yusuf

    Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.

  16. The Effect of β-Glycerophosphate Crosslinking on Chitosan Cytotoxicity and Properties of Hydrogels for Vaginal Application

    Directory of Open Access Journals (Sweden)

    Emilia Szymaǹska

    2015-11-01

    Full Text Available Mucoadhesive gelling systems based on chitosan and chitosan/β-glycerophosphate (β-GP were developed in order to increase clotrimazole residence time in the vaginal cavity. Ex vivo mucoadhesiveness using porcine vaginal mucosa followed with mechanical, viscoelastic, and swelling properties of prepared hydrogels were evaluated. Drug-free, sterile, unmodified, and β-GP crosslinked chitosan were investigated for the in vitro cytotoxicity in CRL 2616 human vaginal mucosa cells using MTT assay, fluorescent microscopy, and flow cytometry analysis. Chitosan/β-GP hydrogels exhibited pseudoplastic and thixotropic properties. Ionic interaction between β-GP and chitosan improved mechanical properties of hydrogels in terms of hardness, cohesiveness, and compressibility. The hydrogels’ ability to interact with porcine vaginal mucosa (measured as force of detachment and work of adhesion was comparable to those obtained with reference mucoadhesive gel Replens™. Surprisingly, greater mucoadhesive properties were noticed for chitosan/β-GP hydrogels. The cytotoxic effect of unmodified and β-GP crosslinked chitosan was hardly affected by chitosan molecular weight, exhibited mainly through inducing apoptosis, and was found to be significantly lower in the presence of chitosan/β-GP. Furthermore, the higher amount of β-GP was used to crosslink chitosan, the lower cytotoxic effect was observed.

  17. The effect of an Annona muricata leaf extract on nutritional status and cytotoxicity in colorectal cancer: a randomized controlled trial.

    Science.gov (United States)

    Indrawati, Lili; Ascobat, Purwantyastuti; Bela, Budiman; Abdullah, Murdani; Surono, Ingrid S

    Annona muricata leaf infusion has traditionally been consumed to maintain health, but is now considered for use in treating cancer patients. The objective of this study was to elucidate the effects of A. muricata leaf extract in humans and human cell lines. Thirty outpatients with colorectal cancer who had undergone primary tumor resection were enrolled in a randomized double-blind placebo- controlled pre-post-trial. They were divided into two groups: those who ingested A. muricata leaf extract (n=14) and those who ingested a placebo (n=14) daily for 8 weeks. Twenty-eight subjects completed the trial; they were equally distributed between the two groups. Serum from patients of both groups was compared for cytotoxicity against colorectal cancer cell lines. The nutritional status of patients was monitored throughout the study. Ex vivo and clinical studies showed higher cytotoxicity in the supplemented group compared with the placebo group. Further research is required to investigate the long-term effect of A.muricata leaf extract, particularly on parameters directly related to cytotoxic activity toward colorectal cancer cells and nutrition status.

  18. Decreasing effect of an anti-Nfa1 polyclonal antibody on the in vitro cytotoxicity of pathogenic Naegleria fowleri

    Science.gov (United States)

    Jeong, Seok-Ryoul; Kang, Su-Yeon; Lee, Sang-Chul; Song, Kyoung-Ju; Im, Kyung-il

    2004-01-01

    The nfa1 gene was cloned from a cDNA library of pathogenic Naegleria fowleri by immunoscreening; it consisted of 360 bp and produced a 13.1 kDa recombinant protein (rNfa1) that showed the pseudopodia-specific localization by immunocytochemistry in the previous study. Based on the idea that the pseudopodia-specific Nfa1 protein mentioned above seems to be involved in the pathogenicity of N. fowleri, we observed the effect of an anti-Nfa1 antibody on the proliferation of N. fowleri trophozoites and the cytotoxicity of N. fowleri trophozoites on the target cells. The proliferation of N. fowleri trophozoites was inhibited after being treated with an anti-Nfa1 polyclonal antibody in a dose-dependent manner for 48 hrs. By a light microscope, CHO cells co-cultured with N. fowleri trophozoites (group I) for 48 hrs showed severe morphological destruction. On the contrary, CHO cells co-cultured with N. fowleri trophozoites and anti-Nfa1 polyclonal antibody (1:100 dilution) (group II) showed less destruction. In the LDH release assay results, group I showed 50.6% cytotoxicity, and group II showed 39.3%. Consequently, addition of an anti-Nfa1 polyclonal antibody produced a decreasing effect of in vitro cytotoxicity of N. fowleri in a dosedependent manner. PMID:15060338

  19. Acute Toxicity and Cytotoxicity Effect of Ethanolic Extract of Spondias tuberosa Arruda Bark: Hematological, Biochemical and Histopathological Evaluation

    Directory of Open Access Journals (Sweden)

    HUMBERTO M. BARBOSA

    Full Text Available ABSTRACT Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. This study evaluated the phytochemical profile and acute toxicity and citoxicity of Ethanolic Extract of Spondias tuberosa Arruda Bark (EEStb in hematological, biochemical and histopathological parameters. Female Wistar rats were divided into: control (C and animal treated single doses of 300mg/Kg (EEStb300 or 2.000mg/kg body weight (ESStb2.000 of the EEStb. After 24 hours and 14 days from gavage, the behavior, hematological, biochemical and histopathological parameters were assayed. Cytotoxicity effect was evaluated on HEp-2 cell lines. Neither EEStb300 nor EEStb2.000 produced mortality nor changes in body weight during the 14-days of observation, but EEStb2.000 reduced quietly the food and water intake as well as locomotor activity at first day. There were no changes in macroscopic, histopathological, biochemical and hematological parameters. EEStb in concentrations of 6.25- 50μg ml−1 on HEp-2 cell did not produce cytotoxic effect. These results suggest that EEStb did not cause acute toxicity and cytotoxic, suggesting a good safety rate for Spondias tuberosa Arruda.

  20. Acute Toxicity and Cytotoxicity Effect of Ethanolic Extract of Spondias tuberosa Arruda Bark: Hematological, Biochemical and Histopathological Evaluation.

    Science.gov (United States)

    Barbosa, Humberto M; Nascimento, Jailson N DO; Araújo, Thiago A S; Duarte, Filipe S; Albuquerque, Ulysses P; Vieira, Jeymesson R C; Santana, Edson R B DE; Yara, Ricardo; Lima, Cláudia S A; Gomes, Dayane A; Lira, Eduardo C

    2016-01-01

    Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. This study evaluated the phytochemical profile and acute toxicity and citoxicity of Ethanolic Extract of Spondias tuberosa Arruda Bark (EEStb) in hematological, biochemical and histopathological parameters. Female Wistar rats were divided into: control (C) and animal treated single doses of 300mg/Kg (EEStb300) or 2.000mg/kg body weight (ESStb2.000) of the EEStb. After 24 hours and 14 days from gavage, the behavior, hematological, biochemical and histopathological parameters were assayed. Cytotoxicity effect was evaluated on HEp-2 cell lines. Neither EEStb300 nor EEStb2.000 produced mortality nor changes in body weight during the 14-days of observation, but EEStb2.000 reduced quietly the food and water intake as well as locomotor activity at first day. There were no changes in macroscopic, histopathological, biochemical and hematological parameters. EEStb in concentrations of 6.25- 50μg ml-1 on HEp-2 cell did not produce cytotoxic effect. These results suggest that EEStb did not cause acute toxicity and cytotoxic, suggesting a good safety rate for Spondias tuberosa Arruda.

  1. Low concentration of quercetin antagonizes the cytotoxic effects of anti-neoplastic drugs in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available The role of Quercetin in ovarian cancer treatment remains controversial, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of Quercetin in combination with Cisplatin and other anti-neoplastic drugs in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action.Quercetin treatment at various concentrations was examined in combination with Cisplatin, taxol, Pirarubicin and 5-Fu in human epithelial ovarian cancer C13* and SKOV3 cells. CCK8 assay and Annexin V assay were for cell viability and apoptosis analysis, immunofluorescence assay, DCFDA staining and realtime PCR were used for reactive oxygen species (ROS-induced injury detection and endogenous antioxidant enzymes expression. Athymic BALB/c-nu nude mice were injected with C13*cells to obtain a xenograft model for in vivo studies. Immunohistochemical analysis was carried out to evaluate the ROS-induced injury and SOD1 activity of xenograft tumors.Contrary to the pro-apoptotic effect of high concentration (40 µM-100 µM of Quercetin, low concentrations (5 µM-30 µM of Quercetin resulted in varying degrees of attenuation of cytotoxicity of Cisplatin treatment when combined with Cisplatin. Similar anti-apoptotic effects were observed when Quercetin was combined with other anti-neoplastic agents: Taxol, Pirarubicin and 5-Fluorouracil (5-Fu. Low concentrations of Quercetin were observed to suppress ROS-induced injury, reduce intracellular ROS level and increase the expression of endogenous antioxidant enzymes, suggesting a ROS-mediated mechanism of attenuating anti-neoplastic drugs. In xenogeneic model, Quercetin led to a substantial reduction of therapeutic efficacy of Cisplatin along with enhancing the endogenous antioxidant enzyme expression and reducing ROS-induced damage in xenograft tumor tissue.Taken together, these data suggest that Quercetin at low concentrations attenuate the therapeutic effects of Cisplatin

  2. Evaluation of Genotoxic and Cytotoxic Effects in Human Peripheral Blood Lymphocytes Exposed In Vitro to Neonicotinoid Insecticides News

    Science.gov (United States)

    Calderón-Segura, María Elena; Gómez-Arroyo, Sandra; Villalobos-Pietrini, Rafael; Martínez-Valenzuela, Carmen; Carbajal-López, Yolanda; Calderón-Ezquerro, María del Carmen; Cortés-Eslava, Josefina; García-Martínez, Rocío; Flores-Ramírez, Diana; Rodríguez-Romero, María Isabel; Méndez-Pérez, Patricia; Bañuelos-Ruíz, Enrique

    2012-01-01

    Calypso (thiacloprid), Poncho (clothianidin), Gaucho (imidacloprid), and Jade (imidacloprid) are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL) were exposed in vitro to different concentrations of the four insecticides. The genotoxic and cytotoxic effects were evaluated using the alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated using two genotoxicity parameters: tail length and comet frequency. Exposure to 9.5 × 10−6 to 5.7 × 10−5 M Jade; 2.8 × 10−4 to 1.7 × 10−3 M Gaucho; 0.6 × 10−1 to 1.4 × 10−1 M Calypso; 1.2 × 10−1 to 9.5 × 10−1 M Poncho for 2 h induced a significant increase DNA damage with a concentration-dependent relationship. Jade was the most genotoxic of the four insecticides studied. Cytotoxicity was observed in cells exposed to 18 × 10−3 M Jade, 2.0 × 10−3 M Gaucho, 2.0 × 10−1 M Calypso, 1.07 M Poncho, and cell death occurred at 30 × 10−3 M Jade, 3.3 × 10−3 M Gaucho, 2.8 × 10−1 M Calypso, and 1.42 M Poncho. This study provides the first report of genotoxic and cytotoxic effects in PBL following in vitro exposure to commercial neonicotinoid insecticides. PMID:22545045

  3. Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215.

    Science.gov (United States)

    Szereday, Z; Schally, A V; Nagy, A; Plonowski, A; Bajo, A M; Halmos, G; Szepeshazi, K; Groot, K

    2002-04-22

    Some brain tumours, such as glioblastomas express high levels of receptors for bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carrier. This study reports the effect of AN-215 on the growth of U-87MG human glioblastomas xenografted into nude mice. High affinity binding of AN-215 to U-87MG tumours was characterised by an IC(50) value of 4.0+/-0.1 nM, as determined by radioreceptor assays. mRNA analyses revealed the presence of mRNA for BN receptor subtypes 1 and 2. Treatment with AN-215 significantly (P<0.05) extended tumour doubling time from 4.54+/-0.2 days to 8.18+/-1.8 days and inhibited tumour growth as demonstrated by a 69.6% reduction in final tumour volume (P<0.001) and a 64.6% decrease in tumour weight as compared to controls. Cytotoxic radical AN-201 at the same dose was ineffective. The antitumour effect of AN-215 could be blocked by pretreatment with an excess of a bombesin antagonist, indicating that the action of this cytotoxic analogue is receptor-mediated. Our results suggest that patients with inoperable brain tumours such as malignant gliomas may benefit from targeted chemotherapy based on cytotoxic bombesin analogue AN-215. Copyright 2002 Cancer Research UK

  4. Evaluation of Genotoxic and Cytotoxic Effects in Human Peripheral Blood Lymphocytes Exposed In Vitro to Neonicotinoid Insecticides News

    Directory of Open Access Journals (Sweden)

    María Elena Calderón-Segura

    2012-01-01

    Full Text Available Calypso (thiacloprid, Poncho (clothianidin, Gaucho (imidacloprid, and Jade (imidacloprid are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL were exposed in vitro to different concentrations of the four insecticides. The genotoxic and cytotoxic effects were evaluated using the alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated using two genotoxicity parameters: tail length and comet frequency. Exposure to 9.5×10-6 to 5.7×10-5 M Jade; 2.8×10-4 to 1.7×10-3 M Gaucho; 0.6×10-1 to 1.4×10-1 M Calypso; 1.2×10-1 to 9.5×10-1 M Poncho for 2 h induced a significant increase DNA damage with a concentration-dependent relationship. Jade was the most genotoxic of the four insecticides studied. Cytotoxicity was observed in cells exposed to 18×10-3 M Jade, 2.0×10-3 M Gaucho, 2.0×10-1 M Calypso, 1.07 M Poncho, and cell death occurred at 30×10-3 M Jade, 3.3×10-3 M Gaucho, 2.8×10-1 M Calypso, and 1.42 M Poncho. This study provides the first report of genotoxic and cytotoxic effects in PBL following in vitro exposure to commercial neonicotinoid insecticides.

  5. Cellular Uptake and Cytotoxicity of -Lactoglobulin Nanoparticles: The Effects of Particle Size and Surface Charge

    Directory of Open Access Journals (Sweden)

    Ho-Kyung Ha

    2015-03-01

    Full Text Available It is necessary to understand the cellular uptake and cytotoxicity of food-grade delivery systems, such as β-lactoglobulin (β-lg nanoparticles, for the application of bioactive compounds to functional foods. The objectives of this study were to investigate the relationships between the physicochemical properties of β-lg nanoparticles, such as particle size and zeta-potential value, and their cellular uptakes and cytotoxicity in Caco-2 cells. Physicochemical properties of β-lg nanoparticles were evaluated using particle size analyzer. Flow cytometry and confocal laser scanning microscopy were used to investigate cellular uptake and cytotoxicity of β-lg nanoparticles. The β-lg nanoparticles with various particle sizes (98 to 192 nm and zeta-potential values (−14.8 to −17.6 mV were successfully formed. A decrease in heating temperature from 70°C to 60°C resulted in a decrease in the particle size and an increase in the zeta-potential value of β-lg nanoparticles. Non-cytotoxicity was observed in Caco-2 cells treated with β-lg nanoparticles. There was an increase in cellular uptake of β-lg nanoparticles with a decrease in particle size and an increase in zeta-potential value. Cellular uptake β-lg nanoparticles was negatively correlated with particle size and positively correlated with zeta-potential value. Therefore, these results suggest that the particle size and zeta-potential value of β-lg nanoparticles play an important role in the cellular uptake. The β-lg nanoparticles can be used as a delivery system in foods due to its high cellular uptake and non-cytotoxicity.

  6. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines

    Directory of Open Access Journals (Sweden)

    Ding-Kun Kang

    Full Text Available Abstract Background: Local anesthetics (LAs are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. Methods: Melanoma cell lines, A375 and Hs294T, were exposed to 1 h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. Results: Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (p < 0.001, concentration- (p < 0.001, and agent dependant. In both A375 and Hs294T cell lines, minimum cell viability rates were found after 72 h of exposure to these agents. Lidocaine 2% caused a reduction of vital cells to 10% ± 2% and 14% ± 2% in A375 and Hs294T, respectively after 72 h of exposure. Ropivacaine 0.75% after 72 h reduced viable cells to 15% ± 3% and 25% ± 3% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to the combination was 10% ± 2% and 18% ± 2% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to melphalan was 8% ± 1% and 12% ± 2%, in A375 and Hs294T, respectively. Conclusion: LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8.

  7. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines.

    Science.gov (United States)

    Kang, Ding-Kun; Zhao, Li-Yan; Wang, Hong-Li

    Local anesthetics (LAs) are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. Melanoma cell lines, A375 and Hs294T, were exposed to 1h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (pLidocaine 2% caused a reduction of vital cells to 10%±2% and 14%±2% in A375 and Hs294T, respectively after 72h of exposure. Ropivacaine 0.75% after 72h reduced viable cells to 15%±3% and 25%±3% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to the combination was 10%±2% and 18%±2% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to melphalan was 8%±1% and 12%±2%, in A375 and Hs294T, respectively. LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  8. Cytotoxicity and Apoptosis-Inducing Effect of Soybean Broth Cultured with Microorganisms Used in the Production of Fermented Soybean Foods on Human Monoblastic Leukemia U937 Cells

    National Research Council Canada - National Science Library

    Inagaki, Shyuichiro; Kato, Takahiro; Ichige, Kuniyasu

    2014-01-01

    ...), and Tetragenococcus halophilus) used commercially in the production of fermented soybean foods, including miso, soy sauce, natto and tempeh, and examined their cytotoxicity and apoptosis-inducing effect on U937 cells...

  9. Investigation of Astragalus honey and propolis extract's cytotoxic effect on two human cancer cell lines and their oncogen and proapoptotic gene expression profiles

    OpenAIRE

    Hojjat Sadeghi-Aliabadi; Jamal Hamzeh; Mina Mirian

    2015-01-01

    Background: Cancer is one of the major fatal human diseases. Natural products have been used in the treatment of cancer for long time. Bee products including honey and propolis have been introduced for malignancy treatment in recent decades. In this study cytotoxicity of bee products and their effects on the expression of proapoptotic genes have been investigated. Materials and Methods: Cytotoxic effects of Astragalus honey, ethanol extract of propolis and a sugar solution (as control) ag...

  10. The protective effects of silybin on the cytotoxicity of thiram in human, rat and chicken cell cultures.

    Science.gov (United States)

    Radko, Lidia; Cybulski, Wojciech; Rzeski, Wojciech

    2017-11-01

    The study objective was a determination of thiram cytotoxicity and silybin cytoprotective activity in course of the fungicide impact on cell metabolism and membrane integrity. Firstly, human, rat, chicken hepatoma cells and rat myoblasts cultures were incubated with thiram. The results showed higher sensitivity of myoblasts on thiram exposure than the hepatoma cells. Among hepatoma cells, the chicken cultures were the most sensitive on the fungicide endangering. The mitochondrial activity was the most thiram affected function within all types the cell lines used. When silybin co-acted with thiram, an increase of the cell viability was recorded. The EC50-values were higher for thiram subjected to interaction with silybin than the effect of alone thiram action. The interaction mode between the studied compounds shown by combination index (CI) represented an antagonistic or an additive nature and was depended on thiram concentration, type of the cells and the assay used. Moreover, the morphology changes were dependent on silybin presence in the cell cultures subjected to thiram impact at the same time. Staining with Hoechst 33342 and propidium ioidium revealed the apoptosis cell death in the incubation cultures. Definitely, the results have shown a potential of silybin to protect the cultured cells in course of cytotoxicity induced by thiram. However, future studies taking into account other endpoints of thiram cytotoxicity pathways including species differences and the cytoprotection efficacy could be of interest. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Genotoxic, cytotoxic, developmental and survival effects of tritiated water in the early life stages of the marine mollusc, Mytilus edulis

    Energy Technology Data Exchange (ETDEWEB)

    Hagger, Josephine A. [School of Biological Sciences, University of Plymouth, Drake Circus, Devon, Plymouth PL4 8AA (United Kingdom); Atienzar, Franck A. [School of Biological Sciences, University of Plymouth, Drake Circus, Devon, Plymouth PL4 8AA (United Kingdom); Jha, Awadhesh N. [School of Biological Sciences, University of Plymouth, Drake Circus, Devon, Plymouth PL4 8AA (United Kingdom)]. E-mail: ajha@plymouth.ac.uk

    2005-09-10

    Using an integrated approach linking different levels of biological organisation, the genotoxic, cytotoxic, developmental and survival impact of tritiated water (HTO) were investigated in the embryo-larvae of marine mollusc Mytilus edulis. One-hour-old embryos were exposed to a range of concentrations (0.37-370 kBq ml{sup -1}) of HTO, which delivered a dose between 0.02 and 21.41 mGy over the exposure period for different end points. Detrimental effects, if any, were monitored at different levels of biological organisation (i.e. DNA, chromosomal, cellular and individual). Genotoxic effects were assessed using molecular and cytogenetic approaches which included analysis of random amplified polymorphic DNA (RAPD), induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (Cabs). Cytotoxic effects were evaluated by determining the proliferative rate index (PRI) of the embryo-larval cells. Developmental and survival effects were also monitored every 24 h up to 72 h. Results in general indicated that HTO significantly increased cytogenetic damage, cytotoxicity, developmental abnormalities and mortality of the embryo-larvae as a function of concentration or radiation dose. The analysis of RAPD profiles also revealed qualitative effects in the HTO exposed population compared to controls. However, while the embryo-larvae showed dose or concentration dependent effects for mortality, developmental abnormalities and induction of SCEs, the dose-dependent effects were not apparent for Cabs and PRI at higher doses. The study contributes to our limited understanding of the impact of environmentally relevant radionuclides on non-human biota and emphasises the need for further investigations to elucidate potentially long term damage induced by persistent, low levels of other radionuclides on commercially and ecologically important species, in order to protect human and ecosystem health.

  12. The cytotoxicity study of praziquantel enantiomers

    Directory of Open Access Journals (Sweden)

    Sun Q

    2016-06-01

    Full Text Available Qian Sun, Ruifeng Mao, Dongling Wang, Changyan Hu, Yang Zheng, Dequn Sun Department of Pharmacy, Marine College, Shandong University, Weihai, People’s Republic of China Abstract: Praziquantel (PZQ is prescribed as a racemic mixture (racemic-PZQ, rac-PZQ, which is composed of (R-PZQ and (S-PZQ. In this work, the cytotoxicity of rac-PZQ and its two enantiomers (R-PZQ and (S-PZQ on eight cell lines (L-02, HepG2, prf-plc-5, SH-SY5Y, HUVEC, A549, HCT-15, Raw264.7 was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. The morphology of apoptotic cells was studied by fluorescence microscope using Hoechst 33342 staining, and the cytotoxicity of the compounds was also tested by lactate dehydrogenase assay. Results revealed that (R-PZQ had negligible cytotoxicity against L-02, SH-SY5Y, HUVEC, A549, HCT-15, and Raw264.7 cells but selectively inhibited tumor cell lines (prf-plc-5 and HepG2. However, in contrast to (R-PZQ, the (S-isomer showed higher cytotoxicity against L-02 cells and lower inhibition on prf-plc-5 and HepG2 cells. Besides, (R-PZQ showed lower cytotoxicity on SH-SY5Y cells than (S-PZQ. Meanwhile, (R-PZQ at <80 µM concentration could promote proliferation of macrophage cells (Raw264.7. Our research revealed that (R-PZQ has lower cytotoxicity than (S-PZQ and has similar cytotoxicity with rac-PZQ. (S-PZQ is the principal enantiomer to cause side effects on human definitive hosts. These findings gave the reasonable reasons for World Health Organization to produce (R-PZQ as a replacement for rac-PZQ for the treatment of schistosomiasis. Keywords: isomer, MTT, selectivity, (R-PZQ

  13. Protective effects of lichen metabolites evernic and usnic acids against redox impairment-mediated cytotoxicity in central nervous system-like cells.

    Science.gov (United States)

    Fernández-Moriano, Carlos; Divakar, Pradeep Kumar; Crespo, Ana; Gómez-Serranillos, M Pilar

    2017-07-01

    Lichens species produce unique secondary metabolites that attract increasing pharmacological interest, including their redox modulatory activities. Current work evaluated for the first time the in vitro cytoprotective properties, based on the antioxidant activities, of the Parmeliaceae lichens Evernia prunastri and Usnea ghattensis and the mechanism of action of their major phenolic constituents: the evernic and usnic acids, respectively. In two models of central nervous system-like cells (U373-MG and SH-SY5Y cell lines), exogenous H2O2 induced oxidative stress-mediated cytotoxicity. We first assessed their radical scavenging capacities (ORAC and DPPH tests) and the phenolic content of the extracts. At the optimal concentrations, pretreatments with evernic acid displayed significant protection against H2O2-induced cytotoxic damage in both models. It reversed the alterations in oxidative stress markers (including ROS generation, glutathione system and lipid peroxidation levels) and cellular apoptosis (caspase-3 activity). Such effects were in part mediated by a notable enhancement of the expression of intracellular phase-II antioxidant enzymes; a plausible involvement of the Nrf2 cytoprotective pathway is suggested. Usnic acid exerted similar effects, to some extent more moderate. Results suggest that lichen polyketides evernic and usnic acids merit further research as promising antioxidant candidates in the therapy of oxidative stress-related diseases, including the neurodegenerative disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Chemical composition and in vitro cytotoxic effects of the essential oil from Nectandra leucantha leaves.

    Science.gov (United States)

    Grecco, Simone dos S; Martins, Euder Glendes A; Girola, Natália; de Figueiredo, Carlos R; Matsuo, Alisson L; Soares, Marisi G; Bertoldo, Bruno de C; Sartorelli, Patricia; Lago, João Henrique G

    2015-01-01

    Nectandra (Lauraceae) species have been used in folk medicine as an antidiarrheal, analgesic, antifungal, etc., and have many pharmacological proprieties. Investigation of the chemical composition and cytotoxicity of essential oil from Nectandra leucantha Nees & Mart. leaves. This is the first study involving N. leucantha reported in the literature. The essential oil of N. leucantha leaves was obtained by hydrodistillation. Its chemical composition was determined using a combination of GC/FID, GC/MS, and determination of Kovats index (KI). In vitro cytotoxic activity was evaluated against six cancer cell lines - murine melanoma (B16F10-Nex2), human glioblastome (U-87), human cervical carcinoma (HeLa), human colon carcinoma (HCT), human breast adenocarcinoma (MCF7), and human cervical tumor (Siha) as well as against one non-tumorigenic cell line - human foreskin fibroblast (HFF). Thirty-three compounds were identified primarily sesquiterpenes (81.41%), the main compounds being bicyclogermacrene (28.44%), germacrene A (7.34%), spathulenol (5.82%), and globulol (5.25%). Furthermore, monoterpenes were also found in the analyzed oil (12.84%), predominantly α- and β-pinenes (6.59 and 4.57%, respectively). The crude essential oil displayed significant cytotoxic activity against B16F10-Nex2 (IC50 33 ± 1 μg/mL) and U87 (IC50 75.95 ± 0.03 μg/mL) and HeLa (IC50 60 ± 12 μg/mL) cell lines. The main identified compound, bicyclogermacrene, displayed IC50 ranging from 3.1 ± 0.2 to 21 ± 6 μg/mL. The results indicate that the crude oils from leaves of N. leucantha displayed cytotoxic activity being bicyclogermacrene, the main compound identified in the crude oil responsible, at least in part, for this potential.

  15. Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line.

    Science.gov (United States)

    Ruffa, M J; Ferraro, G; Wagner, M L; Calcagno, M L; Campos, R H; Cavallaro, L

    2002-03-01

    Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts.

  16. Purvalanol A, olomoucine II and roscovitine inhibit ABCB1 transporter and synergistically potentiate cytotoxic effects of daunorubicin in vitro.

    Directory of Open Access Journals (Sweden)

    Daniela Cihalova

    Full Text Available Cyclin-dependent kinase inhibitors (CDKi have high potential applicability in anticancer therapy, but various aspects of their pharmacokinetics, especially their interactions with drug efflux transporters, have not yet been evaluated in detail. Thus, we investigated interactions of five CDKi (purvalanol A, olomoucine II, roscovitine, flavopiridol and SNS-032 with the ABCB1 transporter. Four of the compounds inhibited efflux of two ABCB1 substrates, Hoechst 33342 and daunorubicin, in MDCKII-ABCB1 cells: Olomoucine II most strongly, followed by roscovitine, purvalanol A, and flavopiridol. SNS-032 inhibited ABCB1-mediated efflux of Hoechst 33342 but not daunorubicin. In addition, purvalanol A, SNS-032 and flavopiridol lowered the stimulated ATPase activity in ABCB1 membrane preparations, while olomoucine II and roscovitine not only inhibited the stimulated ATPase but also significantly activated the basal ABCB1 ATPase, suggesting that these two CDKi are ABCB1 substrates. We further revealed that the strongest ABCB1 inhibitors (purvalanol A, olomoucine II and roscovitine synergistically potentiate the antiproliferative effect of daunorubicin, a commonly used anticancer drug and ABCB1 substrate, in MDCKII-ABCB1 cells as well as in human carcinoma HCT-8 and HepG2 cells. We suggest that this pronounced synergism is at least partly caused by (i CDKi-mediated inhibition of ABCB1 transporter leading to increased intracellular retention of daunorubicin and (ii native cytotoxic activity of the CDKi. Our results indicate that co-administration of the tested CDKi with anticancer drugs that are ABCB1 substrates may allow significant dose reduction in the treatment of ABCB1-expressing tumors.

  17. Cytotoxic effects of peanut phenolics possessing histone deacetylase inhibitory activity in breast and cervical cancer cell lines.

    Science.gov (United States)

    Saenglee, Somprasong; Jogloy, Sanun; Patanothai, Aran; Leid, Mark; Senawong, Thanaset

    2016-12-01

    Epigenetic histone modifications are considered as a promising avenue for cancer preventive and therapeutic strategies. The purpose of this study was to evaluate the antiproliferative and histone deacetylase (HDAC) inhibitory activity of selected peanut phenolics, including p-coumaric acid, ferulic acid, sinapinic acid and resveratrol, in MCF-7 and HeLa cells. The cytotoxic and HDAC inhibitory activities were assessed by MTT assays, flow cytometric analyses of cell cycle arrest and apoptosis induction, and western blotting. The results showed that all four phenolics inhibited proliferation of both MCF-7 and HeLa cells in a dose-dependent manner. Among the phenolics tested, resveratrol was the most effective in inhibiting growth of cancer cells. Treatment with all phenolics resulted in histone H3 hyperacetylation in both cell lines, indicating potential for HDAC inhibition. These phenolics induced apoptosis in both MCF-7 and HeLa cells in a concentration-dependent manner. Moreover, all phenolics induced G0/G1-phase arrest of the cell cycle in MCF-7 cells while p-coumaric and ferulic acids caused S-phase arrest in HeLa cells. Exposure to p-coumaric acid increased p53 and p21 expression but decreased CDK4 levels in both cell types, which could result in the observed G0/G1 arrest. Moreover, inhibition of ERK1/2 phosphorylation by ferulic acid and resveratrol contributed to cell growth inhibition. Peanut phenolics appear to influence the extent of histone acetylation in MCF-7 and HeLa cells, and this activity modulates multiple pathways that are implicated in cancer prevention. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. All rights reserved.

  18. Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Netchareonsirisuk, Ponsawan [Chulalongkorn University, Program in Biotechnology, Faculty of Science (Thailand); Puthong, Songchan [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand); Dubas, Stephan [Chulalongkorn University, Petroleum and Petrochemical College (Thailand); Palaga, Tanapat [Chulalongkorn University, Department of Microbiology, Faculty of Science (Thailand); Komolpis, Kittinan, E-mail: kittinan.k@chula.ac.th [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand)

    2016-11-15

    Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5–15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO{sub 3} alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC{sub 50}), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84–90 %) than necrosis (8–12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

  19. Cytotoxic and apoptotic effect of mycotoxins in human small intestinal cells

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Sørensen, Izel Fourie; Sørensen, Jens Laurids

    2016-01-01

    for consumers and for animal health and welfare. The aim of the present study was to determine the cytotoxicity of several mycotoxins potentially present in feed and food in a sensitive screening assay with normal human small intestinal cells (FHs 74 Int.). For cytotoxicity studies, cells were treated...... with mycotoxins for 72 h, and viability was measured by AlamarBlue reduction. For apoptosis studies, cells were treated with mycotoxins for 24 h, and apoptosis was measured by caspase 3/7 activation. The half maximal inhibitory concentration (IC50) of mycotoxins was calculated from sigmoidal dose-response plots....... T-2 toxin was the most cytotoxic mycotoxin (6.4 nM), followed by HT-2 toxin (24 nM), PR toxin (44 nM), gliotoxin (0.11 µM), NIV (0.32 µM), deoxynivalenol (DON; 0.34 µM), patulin (0.97 µM), and zearalenone (ZEA; 11 µM). Mycophenolic acid, roquefortine, citrinin, and moniformin did not cause...

  20. Protective effect of kombucha mushroom (KM) tea on phenol-induced cytotoxicity in albino mice.

    Science.gov (United States)

    Yapar, Kursad; Cavusoglu, Kultigin; Oruc, Ertan; Yalcin, Emine

    2010-09-01

    The present study was carried out to evaluate the protective role of kombucha mushroom (KM) tea on cytotoxicity induced by phenol (PHE) in mice. We used weight gain and micronucleus (MN) frequency as indicators of cytotoxicity and supported these parameters with pathological findings. The animals were randomly divided into seven groups: (Group I) only tap water (Group II) 1000 microl kg(-1) b. wt KM-tea, (Group III) 35 mg kg(-1) body wt. PHE (Group IV) 35 mg kg(-1) body wt. PHE + 250 microl kg(-1) b. wt KM-tea (Group V) 35 mg kg(-1) b. wt PHE + 500 microl kg(-1) b. wt KM-tea (Group VI) 35 mg kg(-1) b. wt PHE + 750 microl kg(-1) b. wt KM-tea, (Group VII) 35 mg kg(-1) b. wt PHE + 1000 microl kg(-1) b. wt KM-tea, for 20 consecutive days by oral gavage. The results indicated that all KM-tea supplemented mice showed a lower MN frequency than erythrocytes in only PHE-treated group. There was an observable regression on account of lesions in tissues of mice supplemented with different doses of KM-tea in histopathological observations. In conclusion, the KM-tea supplementation decreases cytotoxicity induced by PHE and its protective role is dose-dependent.

  1. Synergistic cytotoxic effect of tetrachlorocatechol and sodium azide in Escherichia coli: toxicity, metabolism, and mechanistic aspects.

    Science.gov (United States)

    Levy, Smadar; Chevion, Mordechai

    2009-07-01

    Pentachlorophenol (PCP) is used in industrial and domestic applications, including as a biocide and a wood preservative. Metabolism of PCP undergoes oxidative dechlorination, forming tetrachlorocatechol (TCC) and tetrachlorohydroquinone (TCHQ). Both sodium azide (NaN(3)) and TCC appear naturally in soil. None of them are cytotoxic by themselves or facilitate autooxidation. Here, we show that their combination leads to synergistic cytotoxicity (>6 log bacterial killing) to Escherichia coli. The rate of oxygen consumption in a cell-free system showed that NaN(3) increases TCC oxidation by 520-fold. The synergism coefficient to cells was calculated as 96 or greater, and we have shown the formation of a new compound. It is suggested that the intermediate species, o-tetrachlorosemiquinine, and an unknown, nitrogen-centered free radical, both visualized by electron-spin resonance, are harmful species responsible for the synergistic cytotoxicity of TCC/NaN(3), rather than the endproduct formed during the reaction. Desferrioxamine and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide offered nearly complete protection, but through radical scavenging rather than through chelating properties. The mechanism of damage for TCC compared to its analogue, TCHQ, were investigated, and whereas the cellular damage of TCHQ/NaN(3) is through a site-specific mechanism, in the case of TCC/NaN(3) it is through the accumulation of the component(s) in the bacterial cell membrane, eventually leading to dysfunction, as evidenced by electron microscopy.

  2. Cytotoxicity and Apoptotic Effects of Polyphenols from Sugar Beet Molasses on Colon Carcinoma Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Mingshun Chen

    2016-06-01

    Full Text Available Three polyphenols were isolated and purified from sugar beet molasses by ultrasonic-aid extraction and various chromatographic techniques, and their structures were elucidated by spectral analysis. Cytotoxicity and the molecular mechanism were measured by methyl thiazolyl tetrazolium (MTT assay, flow cytometry, caspase-3 activity assay and Western blot assay. The results showed that gallic acid, cyanidin-3-O-glucoside chloride and epicatechin have cytotoxicity to the human colon, hepatocellular and breast cancer cells. Cyanidin-3-O-glucoside chloride showed its cytotoxicity against various tumor cell lines, particularly against colon cancer Caco-2 cells with half maximal inhibitory concentration (IC50 value of 23.21 ± 0.14 μg/mL in vitro. Cyanidin-3-O-glucoside chloride may be a potential candidate for the treatment of colon cancer. In the mechanism study, cyanidin-3-O-glucoside chloride increased the ratio of cell cycle at G0/G1 phase and reduced cyclin D1 expression on Caco-2 cells. Cyanidin-3-O-glucoside chloride decreased mutant p21 expression, and increased the ratio of Bax/Bcl-2 and the activation of caspase-3 to induce apoptosis.

  3. Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity

    Directory of Open Access Journals (Sweden)

    Fahad A. Al-Abbasi

    2016-07-01

    Full Text Available Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl4-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4′-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC50 values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG2 and Huh7, cells decreasing its IC50s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G2/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G2/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics.

  4. Cytotoxity of cell free filtrates of campylobacter jejuni isolated in ...

    African Journals Online (AJOL)

    Culture filtrates of Campylobacter jejuni strains isolated from clinical specimens in Lagos Nigeria were tested for toxic activity. Two out of five filtrates tested manifested cytopathic effect on BHK cells. The effects were mainly cytotoxic and cytotonic. Toxic activity of C. jejuni filtrates was much lower than toxic activity elicited by ...

  5. Exopolysaccharides produced by Lactobacillus and Bifidobacterium strains abrogate in vitro the cytotoxic effect of bacterial toxins on eukaryotic cells.

    Science.gov (United States)

    Ruas-Madiedo, P; Medrano, M; Salazar, N; De Los Reyes-Gavilán, C G; Pérez, P F; Abraham, A G

    2010-12-01

    To evaluate the capability of the exopolysaccharides (EPS) produced by lactobacilli and bifidobacteria from human and dairy origin to antagonize the cytotoxic effect of bacterial toxins. The cytotoxicity of Bacillus cereus extracellular factors on Caco-2 colonocytes in the presence/absence of the EPS was determined by measuring the integrity of the tissue monolayer and the damage to the cell membrane (extracellular lactate dehydrogenase activity). Additionally, the protective effect of EPS against the haemolytic activity of the streptolysin-O was evaluated on rabbit erythrocytes. The EPS produced by Bifidobacterium animalis ssp. lactis A1 and IPLA-R1, Bifidobacterium longum NB667 and Lactobacillus rhamnosus GG were able to counteract the toxic effect of bacterial toxins on the eukaryotic cells at 1mg ml(-1) EPS concentration. The EPS A1 was the most effective in counteracting the effect of B. cereus toxins on colonocytes, even at lower doses (0·5mg ml(-1) ), whereas EPS NB667 elicited the highest haemolysis reduction on erythrocytes. The production of EPS by lactobacilli and bifidobacteria could antagonize the toxicity of bacterial pathogens, this effect being EPS and biological marker dependent. This work allows gaining insight about the mechanisms that probiotics could exert to improve the host health. © 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.

  6. Cytotoxic effect of x-irradiation of mouse tumor cells in the presence of Korean ginseng extract

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyoung Cheol; Kim, Jin Ki; Kim, Jung Soo [College of Medicine, Chonbuk National Univ., Junju (Korea, Republic of); Choi, Dong Seong [College of Medicine, Woosuck Univ., Wanju (Korea, Republic of)

    2000-09-01

    We already reported the results that aqueous extract of Korean ginseng roots showed a marked cytotoxicity. In this study, we investigated whether combined ginseng product with X-irradiation increase the cytotoxicity of tumor cells than X-irradiation or not. Fifty gram of Korean ginseng powder mixed with 1 L of distilled water was extracted with reflux flask under condition of 100 .deg. C for 5 hrs. This aqueous ginseng extract was filtered, centrifuged and then was freezed under condition of -90 .deg. C for 16-18 hrs. The freezing extract was dried with freeze drier, and then diluted. X-irradiation was given to tumor cells by 6 MeV linear accelerator. The cytotoxicity of ginseng in vitro was evaluated from its ability to reduce the clonogenecity of fibrosarcoma (FSa ll) cells. In X-irradiation alone group, each 2, 4, 6 and 8 Gy was given to tumor cells. In X-irradiation with ginseng group, 0.2 mg/mL or ginseng extract was exposed to tumor cells for 1 hour before X-irradiation. The yield for 50 g of ginseng extract which was treated with freezing drier was 3.13 g(6.3%). Cytotoxicity in vitro was measured as survival fraction which was judged from the curve, at ginseng concentration of 0.001, 0.01, 0.1 and 1 mg/ml were 0.89{+-}0.04, 0.86{+-}0.06, 0.73{+-}0.01 and 0.09{+-}0.02, respectively. Survival fraction at X-irradiation alone of 2, 4, 6 and 8 Gy were 0.81{+-}0.07, 0.42{+-}0.08, 0.15{+-}0.02, 0.03{+-}0.01, respectively. But, survival fraction in combined group of X-irradiation and ginseng (0.2mg/mL) at each same radiation dose were 0.28{+-}0.01, 0.18{+-}0.03, 0.08{+-}0.02, 0.006{+-}0.002, respectively (p<0.05). The yield for ginseng extract which was treated with freezing drier was 6.3%. Cytotoxicity of Fsa II in combined ginseng with X-irradiation group was increased than that at X-irradiation alone group, and its enhancing effect seemed to be added.

  7. Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells

    Directory of Open Access Journals (Sweden)

    He Fan

    2010-12-01

    Full Text Available Abstract Background Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. Methods Two cervical cancer cell lines, HeLa and Siha, an ovarian cancer cell line, SKOV3, and a non-small cell lung cancer cell line, A549, were treated with saikosaponins or cisplatin individually or in combination. Cell death was quantitatively detected by the release of lactate dehydrogenase (LDH using a cytotoxicity detection kit. Cellular ROS was analyzed by flow cytometry. Apoptosis was evaluated by AO/EB staining, flow cytometry after Anexin V and PI staining, and Western blot for caspase activation. ROS scavengers and caspase inhibitor were used to determine the roles of ROS and apoptosis in the effects of saikosaponins on cisplatin-induced cell death. Results Both saikosaponin-a and -d sensitized cancer cells to cisplatin-induced cell death in a dose-dependent manner, which was accompanied with induction of reactive oxygen species (ROS accumulation. The dead cells showed typical apoptotic morphologies. Both early apoptotic and late apoptotic cells detected by flow cytometry were increased in saikosaponins and cisplatin cotreated cells, accompanied by activation of the caspase pathway. The pan-caspase inhibitor z-VAD and ROS scanvengers butylated hydroxyanisole (BHA and N-acetyl-L-cysteine (NAC dramatically suppressed the potentiated cytotoxicity achieved by combination of saikosaponin-a or -d and cisplatin. Conclusions These results suggest that saikosaponins sensitize cancer cells to cisplatin through ROS-mediated apoptosis, and the combination of saikosaponins with cisplatin could be an effective therapeutic strategy.

  8. Testing of Binders Toxicological Effects

    Science.gov (United States)

    Strokova, V.; Nelyubova, V.; Rykunova, M.

    2017-11-01

    The article p