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Sample records for moderate antiproliferative activity

  1. Antiproliferative and antibacterial activity evaluation of red ...

    African Journals Online (AJOL)

    sunny

    2014-10-22

    Oct 22, 2014 ... Key words: Rhodosorus marinus, red microalgae, antibacterial activity, antiproliferative activity, methanolic extract. ... subsequent production of metabolites (secondary ..... antioxidant molecules, such as vitamins, enzymes,.

  2. Antiproliferative activity of fucan nanogel.

    Science.gov (United States)

    Dantas-Santos, Nednaldo; Almeida-Lima, Jailma; Vidal, Arthur Anthunes Jacome; Gomes, Dayanne Lopes; Oliveira, Ruth Medeiros; Santos Pedrosa, Silvia; Pereira, Paula; Gama, Francisco Miguel; Oliveira Rocha, Hugo Alexandre

    2012-09-01

    Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated L-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc) formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean diameter of 123 nm and zeta potential of -38.3 ± 0.74 mV, as measured by dynamic light scattering. Nanoparticles conserved their size for up to 70 days. SNFuc cytotoxicity was determined using the MTT assay after culturing different cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5) proliferation was inhibited by 2.0%-43.7% at nanogel concentrations of 0.05-0.5 mg/mL and rabbit aorta endothelial cells (RAEC) non-tumor cell line proliferation displayed inhibition of 8.0%-22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO) and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same concentration range. The antiproliferative effect against tumor cells was also confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle.

  3. Antiproliferative Activity of Fucan Nanogel

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    Francisco Miguel Gama

    2012-09-01

    Full Text Available Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated l-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean diameter of 123 nm and zeta potential of −38.3 ± 0.74 mV, as measured by dynamic light scattering. Nanoparticles conserved their size for up to 70 days. SNFuc cytotoxicity was determined using the MTT assay after culturing different cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5 proliferation was inhibited by 2.0%–43.7% at nanogel concentrations of 0.05–0.5 mg/mL and rabbit aorta endothelial cells (RAEC non-tumor cell line proliferation displayed inhibition of 8.0%–22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO and monocyte macrophage cell (RAW non-tumor cell line proliferation in the same concentration range. The antiproliferative effect against tumor cells was also confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle.

  4. Phytochemical and antiproliferative activity of proso millet.

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    Lizhen Zhang

    Full Text Available The phytochemical content, antioxidant activity and antiproliferative properties of three diverse varieties of proso millet are reported. The free phenolic content ranged from 27.48 (Gumi 20 to 151.14 (Mi2504-6 mg gallic acid equiv/100 g DW. The bound phenolic content ranged from 55.95 (Gumi20 to 305.81 (Mi2504-6 mg gallic acid equiv/100 g DW. The percentage contribution of bound phenolic to the total phenolic content of genotype samples analyzed ranged between 62.08% and 67.05%. Ferulic acid and chlorogenic acid are the predominant phenolic acid found in bound fraction. Caffeic acid and p-coumaric acid were also detected. Syringic acid was detected only in the free fraction. The antioxidant activity was assessed using the hydrophilic peroxyl radical scavenging capacity (PSC assay. The PSC antioxidant activity of the free fraction ranged from 57.68 (Mi2504-6 to 147.32 (Gumi20 µmol of vitamin C equiv/100 g DW. The PSC antioxidant activity of the bound fraction ranged from 95.38 (Mizao 52 to 136.48 (Gumi 20 µmol of vitamin C equiv/100 g DW. The cellular antioxidant activity (CAA of the extract was assessed using the HepG2 model. CAA value ranged from 2.51 to 6.10 µmol equiv quercetin/100 g DW. Antiproliferative activities were also studied in vitro against MDA human breast cancer and HepG2 human liver cancer cells. Results exhibited a differential and possible selective antiproliferative property of the proso millet. These results may be used to direct the consumption of proso millet with improved health properties.

  5. Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids.

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    Cedrón, Juan C; Ravelo, Ángel G; León, Leticia G; Padrón, José M; Estévez-Braun, Ana

    2015-07-30

    The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined.

  6. Antiproliferative Activity of Flavonoids from Croton sphaerogynus Baill. (Euphorbiaceae

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    Kátia Pereira dos Santos

    2015-01-01

    Full Text Available Croton sphaerogynus is a shrub from the Atlantic Rain Forest in southeastern Brazil. A lyophilized crude EtOH extract from leaves of C. sphaerogynus, obtained by maceration at room temperature (seven days, was suspended in methanol and partitioned with hexane. The purified MeOH phase was fractionated over Sephadex LH-20 yielding five fractions (F1–F5 containing flavonoids, as characterized by HPLC-DAD and HPLC-MS analyses. The antiproliferative activity of the crude EtOH extract, MeOH and hexane phases, and fractions F1–F5 was evaluated on in vitro cell lines NCI-H460 (nonsmall cell lung, MCF-7 (breast cancer, and U251 (glioma. The MeOH phase showed activity (mean log GI50 0.54 higher than the hexane phase and EtOH extract (mean log GI50 1.13 and 1.19, resp.. F1 exhibited activity against NCI-H460 (nonsmall cell lung (GI50 1.2 μg/mL, which could be accounted for the presence of flavonoids and/or diterpenes. F4 showed moderate activity (mean log GI50 1.05, while F5 showed weak activity (mean log GI50 1.36. It is suggested that the antiproliferative activity of the crude EtOH extract and MeOH phase is accounted for a synergistic combination of flavonoids and diterpenes.

  7. Antiproliferative activity of flavonoids from Croton sphaerogynus Baill. (Euphorbiaceae).

    Science.gov (United States)

    dos Santos, Kátia Pereira; Motta, Lucimar B; Santos, Deborah Y A C; Salatino, Maria L F; Salatino, Antonio; Ferreira, Marcelo J Pena; Lago, João Henrique G; Ruiz, Ana Lúcia T G; de Carvalho, João E; Furlan, Cláudia M

    2015-01-01

    Croton sphaerogynus is a shrub from the Atlantic Rain Forest in southeastern Brazil. A lyophilized crude EtOH extract from leaves of C. sphaerogynus, obtained by maceration at room temperature (seven days), was suspended in methanol and partitioned with hexane. The purified MeOH phase was fractionated over Sephadex LH-20 yielding five fractions (F1-F5) containing flavonoids, as characterized by HPLC-DAD and HPLC-MS analyses. The antiproliferative activity of the crude EtOH extract, MeOH and hexane phases, and fractions F1-F5 was evaluated on in vitro cell lines NCI-H460 (nonsmall cell lung), MCF-7 (breast cancer), and U251 (glioma). The MeOH phase showed activity (mean log GI50 0.54) higher than the hexane phase and EtOH extract (mean log GI50 1.13 and 1.19, resp.). F1 exhibited activity against NCI-H460 (nonsmall cell lung) (GI50 1.2 μg/mL), which could be accounted for the presence of flavonoids and/or diterpenes. F4 showed moderate activity (mean log GI50 1.05), while F5 showed weak activity (mean log GI50 1.36). It is suggested that the antiproliferative activity of the crude EtOH extract and MeOH phase is accounted for a synergistic combination of flavonoids and diterpenes.

  8. Antiproliferative activity of Vallaris glabra Kuntze (Apocynaceae

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    Siu Kuin Wong

    2014-01-01

    Full Text Available Background: Our earlier study on the antiproliferative (APF activity of leaf extracts of ten Apocynaceae species showed that leaves of Vallaris glabra possessed strong and broad-spectrum properties. Materials and Methods: In this study, sequential extracts of leaves, flowers and stems, and fractions and isolated compounds from dichloromethane (DCM leaf extract of V. glabra were assessed for APF activity using the sulphorhodamine B (SRB assay. Apoptotic effect of MDA-MB-231 cancer cells treated with DCM leaf extract of V. glabra was studied using Hoechst 33342 dye and caspase colorimetry. Results: Both DCM extracts of leaves and flowers possessed broad-spectrum APF activity against HT-29, MCF-7, MDA-MB-231 and SKOV-3 cancer cells. From DCM leaf extract, stearic acid (SA and ursolic acid (UA were isolated by column chromatography, and identified by NMR and MS analyses. APF activity of SA from DCM leaf extract displayed weak inhibitory activity and scientific literature showed UA has anticancer properties against those cancer cells used in this study. MDA-MB-231 cancer cells treated with DCM leaf extract and stained with Hoechst 33342 dye provided evidence that the extract had an apoptotic effect on the cells. Caspase colorimetry showed that the apoptotic effect involved activation of caspase-8, -9 and -3, but not caspase-6. Conclusion: The potential of V. glabra as a candidate species for anticancer drugs warrants further investigation.

  9. Synthesis and Antiproliferative Activity of Some Quinoline and Oxadiazole Derivatives

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    Mohamed Jawed Ahsan

    2016-01-01

    Full Text Available In continuance of our search for newer antiproliferative agents we report herein the synthesis and antiproliferative studies of two series (5a–j and 10a–c of heterocyclic compounds. All the new compounds were characterized by IR, NMR, and mass spectral data. The antiproliferative activity of 10 compounds (5a–j was carried out on HeLa (cervix cancer cell line and MDA-MB-435 (melanoma and LC50, TGI, and GI50 were calculated, while the antiproliferative activity of 3 compounds (10a–c was carried out against nine different panels of nearly 60 cell lines (NCI-60 according to the National Cancer Institute (NCI US Protocol at 10 μM. 1-(7-Hydroxy-4-methyl-2-oxoquinolin-1(2H-yl-3-(4-methoxylphenylurea (5j was found to have antiproliferative activity with GI50 of 35.1 μM against HeLa (cervix cancer cell line and 60.4 μM against MDA-MB-435 (melanoma, respectively. The compounds 10a, 10b, and 10c showed antiproliferative activity with comparatively higher selectivity towards HOP-92 (Non-Small Cell Lung Cancer with percent growth inhibitions (GIs of 34.14, 35.29, and 31.59, respectively.

  10. Syntehsis and antiproliferative activities of chloropyridazine derivatives retain alkylsulfonyl moiety

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chae Won; Park, Myung Sook [College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of)

    2016-11-15

    Some chloropyridazine derivatives have shown interesting pharmacodynamics properties in terms of antioxidant and anti-human rotavirus (HRV) activities (Figure 1). To date, however, no study has evaluated the antiproliferative effects of chloropyridazines in other types of human cancer cells. In conclusion, we designed and synthesized a total of five groups of alkoxy-(or alkylthio-, alkylselenyl-, alkylsufinyl alkylsulfonyl-)chloropyridazines, and their antiproliferative activity was evaluated in the human cancer cell lines. IC{sub 50} values showed that the alkylsulfonylchloropyridazine compounds exhibited more active than the other four groups having alkoxy, alkylthio, alkylselenyl, alkylsulfinyl moieties against MCF-7 and Hep2B Cells.

  11. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

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    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Beta-lactam type molecular scaffolds for antiproliferative activity: synthesis and cytotoxic effects in breast cancer cells.

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    Meegan, Mary J; Carr, Miriam; Knox, Andrew J S; Zisterer, Daniela M; Lloyd, David G

    2008-10-01

    A series of novel beta-lactam containing compounds are described as antiproliferative agents and potential selective modulators of the oestrogen receptor. The purpose of the study is to evaluate the antiproliferative effects of these compounds on human MCF-7 and MDA MB-231 breast cancer cells. The compounds are designed to contain three aryl ring substituents arranged on the heterocyclic azetidin-2-one (beta-lactam), thus providing conformationally restrained analogues of the triarylethylene arrangement exemplified in the tamoxifen type structure. The compounds demonstrated potency in antiproliferative assays against MCF-7 human breast cancer cell line at low micromolar to nanomolar concentrations with low cytotoxicity and moderate binding affinity to the oestrogen receptor. The effect of a number of aryl and amine functional group substitutions on the antiproliferative activity of the beta-lactam products was explored and a brief computational structure-activity relationship investigation with molecular simulation was investigated.

  13. Five new diarylheptanoids from the rhizomes of Curcuma kwangsiensis and their antiproliferative activity.

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    Chen, Shao-Dan; Gao, Jin-Tao; Liu, Jing-Gong; Liu, Bo; Zhao, Rui-Zhi; Lu, Chuan-Jian

    2015-04-01

    Five new diarylheptanoids (1-5), along with nine known ones (6-14), were isolated from the rhizomes of Curcuma kwangsiensis. Their structures were established on the basis of spectroscopic analyses. Compounds 1-3 were cyclic diarylheptanoids rarely discovered from C. kwangsiensis. Of all the isolated compounds, compound 4 showed moderate antiproliferative activity on HH and HaCaT cells. Copyright © 2015. Published by Elsevier B.V.

  14. In Vitro Antimicrobial and Antiproliferative Activity of Amphipterygium adstringens

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    A. Rodriguez-Garcia

    2015-01-01

    Full Text Available Amphipterygium adstringens is a plant widely used in Mexican traditional medicine for its known anti-inflammatory and antiulcer properties. In this work, we evaluated the in vitro antimicrobial and antiproliferative activities of the methanolic extract of A. adstringens against oral pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Candida albicans, and Candida dubliniensis, using microdilution (MIC and agar diffusion methods (MBC, and the antiproliferative activity evaluating total growth inhibition (TGI by staining the protein content with sulforhodamine B (SRB, using nine human cancer cell lines. Crude extract (CE of A. adstringens showed some degree of activity against one or more of the strains with a MIC from 0.125 mg/mL to 63 mg/mL and MBC from 1.6 to 6.3 mg/mL and cytotoxic activity, particularly against NCI-ADR/RES, an ovarian cell line expressing multiple resistance drugs phenotype. The CE is a complex mixture of possible multitarget metabolites that could be responsible for both antimicrobial and antiproliferative activities, and further investigation is required to elucidate the identity of active compounds. Nevertheless the CE itself is useful in the development of new antimicrobial treatment based on natural products to prevent oral diseases and as alternative natural source for cancer treatment and prevention.

  15. Bioactivity-guided study of antiproliferative activities of Salvia extracts.

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    Janicsák, Gábor; Zupkó, István; Nikolovac, Milena T; Forgo, Peter; Vasas, Andrea; Mathé, Imre; Blunden, Gerald; Hohmann, Judit

    2011-05-01

    The cytotoxic activities of the n-hexane, chloroform and aqueous methanolic fractions prepared from the methanolic extract of the leaves of 23 Salvia taxa were studied for their cell growth-inhibitory activity against human cervix adenocarcinoma (HeLa), skin carcinoma (A431) and breast adenocarcinoma (MCF7) cells using the MTT assay. The n-hexane fractions of six Salvia taxa (S. hispanica, S. nemorosa, S. nemorosa 1. albiflora, S. pratensis, S. recognita and S. ringens) and the chloroform fraction ofS. officinalis 1. albiflora produced over 50% growth inhibition of the skin carcinoma cell line. None of the tested extracts showed substantial (above 50%) antiproliferative effects against HeLa and MCF7 cells. S. ringens was the most powerful among the studied Salvia species with a 61.8% cell growth inhibitory activity on A431 cells. In the case of S. ringens, other plant parts were also tested for antiproliferative effect, and the highest activities were recorded for the root extract. This was subjected to bioactivity-guided fractionation, which yielded four abietane diterpenes (royleanone, horminone, 7-O-methyl-horminone and 7-acetyl-horminone), one triterpene (erythrodiol-3-acetate) and beta-sitosterol. Horminone, 7-acetyl-horminone and erythrodiol-3-acetate displayed marked concentration-dependent antiproliferative effects, while royleanone and 7-O-methyl-horminone produced weaker activities.

  16. Antioxidant and antiproliferative activity of Granny Smith apple pomace

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    Savatović Slađana M.

    2008-01-01

    Full Text Available Granny Smith apple pomace was subjected to evaluation as valuable source of antioxidant and anticancer phytochemicals on the basis of its content in phenolic compounds, antioxidant and antiproliferative activity. The total cotent of phenolics, flavonoids and flavan-3-ols in apple pomace determined spectrophotometrically, was 7.02 mg/g, 0.51 mg/g and 8.80 mg/g. Major phenolics (phenolic acids, flavan-3-ols, flavonoids and dihydrochalcons in apple pomace were identified and quantified by HPLC. The antioxidant activity of apple pomace on stable 1,1-diphenyl-2-picrylhydrazyl (DPPH and reactive hydroxyl radicals, was investigated by electron spin resonance (ESR spectroscopy. The IC50 DPPH and IC50 OH values of Granny Smith apple pomace were 9.51 mg/ml and 29.17 mg/ml, respectively. The antiproliferative activities of apple pomace on cervix epitheloid carcinoma (HeLa, colon adenocarcinoma (HT-29 and breast adenocarcinoma (MCF7 cell lines were determined according to the MTT (3-(4,5-dimethylthiazol-2-yl- 2,5-diphenyltetrazolium bromide colorimetric assay. The IC50 HeLa , IC50 HT-29 and IC50 MCF7 values of Granny Smith apple pomace were 26.40 mg/ml, 22.47 mg/ml and 21.26 mg/ml, respectively. The significant correlations between antioxidant activities and antiproliferative activities were established (p<0.05.

  17. Syntheses and Antiproliferative Activities of Novel Diarylthiosemicarbazide Derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHAI Xin; HE Ying; YANG Zhen; GONG Ping

    2013-01-01

    A series of novel N-methylpicolinamide-moiety containing diarylthiosemicarbazide derivatives was prepared and evaluated for their in vitro antiproliferative activity against three cancer cell lines(human alveolar epithelial cell A549,human lung cancer cell H460 and human colorectal cancer cell HT-29) by 3-(4,5-dimethyl)thiazolyl-diphenyltetrazoliumromide(MTT) assay.Six compounds(7b-7g) with halogen substituents exhibited preferable cytotoxicity against one or more cell lines in a low micromolar range.Especially,the most promising compound 7g exhibited remarkable antiproliferative activity with the IC50 values of 2.2,1.8 and 5.2 μmol/L against A549,H460 and HT-29 cell lines respectively,which is comparable to sorafenib.

  18. Rosmarinus officinalis essential oil: antiproliferative, antioxidant and antibacterial activities

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    Abdullah Ijaz Hussain

    2010-12-01

    Full Text Available The aim of this work was to investigate and compare the antiproliferative, antioxidant and antibacterial activities of Rosmarinus officinalis essential oil, native to Pakistan. The essential oil content from the leaves of R. officinalis was 0.93 g 100g-1. The GC and GC-MS analysis revealed that the major components determined in R. officinalis essential oil were 1,8-cineol (38.5%, camphor (17.1%, α-pinene (12.3%, limonene (6.23%, camphene (6.00% and linalool (5.70%. The antiproliferative activity was tested against two cancer (MCF-7 and LNCaP and one fibroblast cell line (NIH-3T3 using the MTT assay, while, the antioxidant activity was evaluated by the reduction of 2, 2-diphenyl-1-picryl hydrazyl (DPPH and measuring percent inhibition of peroxidation in linoleic acid system. The disc diffusion and modified resazurin microtitre-plate assays were used to evaluate the inhibition zones (IZ and minimum inhibitory concentration (MIC of R. officinalis essential oil, respectively. It is concluded from the results that Rosmarinus officinalis essential oil exhibited antiproliferative, antioxidant and antibacterial activities.

  19. Evaluating Antiproliferative and Antioxidant Activity of Marrubium crassidens

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    Sanaz Hamedeyazdan

    2014-10-01

    Full Text Available Purpose: Naturally occurring substances as novel drugs in cancer therapy, at all times, represent a challenge to science since medicinal plants are proving to be brilliant sources of new chemopreventive agents. Methods: In the present study, methanol extract from aerial parts of Marrubium crassidens was assessed for its antiproliferative activity in the breast cancer cell line MCF-7 through MTT bioassay using cell viability and cytotoxicity indices. The antioxidant property of M. crassidens extract together with its phenolic and flavonoids content were evaluated, as well. Results: According to data obtained in the study, M. crassidens exhibited antiproliferative activity with a gradual rise in cytotoxicty effect setting out on 240μg/mL concentration of the extract. Moreover, the RC50 value for antioxidant activity of the extract was determined as 40μg/mL and values for the total phenolic and flavonoids were calculated as 512.64mg gallic acid equivalent and 212.73mg quercetin equivalent per 100g of dry plant material. Conclusion: Generally, the observed antiproliferative and antioxidant properties of M. crassidens could be certified to the high amounts of phenolic and flavonoid content detected in the extract.

  20. Characterization and Antiproliferative Activity of Nobiletin-Loaded Chitosan Nanoparticles

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    Ana G. Luque-Alcaraz

    2012-01-01

    Full Text Available Nobiletin is a polymethoxyflavonoid with a remarkable antiproliferative effect. In order to overcome its low aqueous solubility and chemical instability, the use of nanoparticles as carriers has been proposed. This study explores the possibility of binding nobiletin to chitosan nanoparticles, as well as to evaluate their antiproliferative activity. The association and loading efficiencies are 69.1% and 7.0%, respectively. The formation of an imine bond between chitosan amine groups and the carbonyl group of nobiletin, via Schiff-base, is proposed. Nobiletin-loaded chitosan nanoparticles exhibit considerable inhibition (IC50=8 μg/mL of cancerous cells, revealing their great potential for applications in cancer chemotherapy.

  1. Synthesis, antiproliferative activity and molecular docking of Colchicine derivatives.

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    Huczyński, Adam; Majcher, Urszula; Maj, Ewa; Wietrzyk, Joanna; Janczak, Jan; Moshari, Mahshad; Tuszynski, Jack A; Bartl, Franz

    2016-02-01

    In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to β-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods.

  2. Antioxidant and antiproliferative activities of common fruits.

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    Sun, Jie; Chu, Yi-Fang; Wu, Xianzhong; Liu, Rui Hai

    2002-12-01

    Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.

  3. Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues.

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    Daniel Nascimento do Amaral

    Full Text Available Cancer is the second most common cause of death in the USA. Among the known classes of anticancer agents, the microtubule-targeted antimitotic drugs are considered to be one of the most important. They are usually classified into microtubule-destabilizing (e.g., Vinca alkaloids and microtubule-stabilizing (e.g., paclitaxel agents. Combretastatin A4 (CA-4, which is a natural stilbene isolated from Combretum caffrum, is a microtubule-destabilizing agent that binds to the colchicine domain on β-tubulin and exhibits a lower toxicity profile than paclitaxel or the Vinca alkaloids. In this paper, we describe the docking study, synthesis, antiproliferative activity and selectivity index of the N-acylhydrazone derivatives (5a-r designed as CA-4 analogues. The essential structural requirements for molecular recognition by the colchicine binding site of β-tubulin were recognized, and several compounds with moderate to high antiproliferative potency (IC50 values ≤18 µM and ≥4 nM were identified. Among these active compounds, LASSBio-1586 (5b emerged as a simple antitumor drug candidate, which is capable of inhibiting microtubule polymerization and possesses a broad in vitro and in vivo antiproliferative profile, as well as a better selectivity index than the prototype CA-4, indicating improved selective cytotoxicity toward cancer cells.

  4. Synthesis and antiproliferative activity of new tonantzitlolone-derived diterpene derivatives.

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    Busch, Torsten; Dräger, Gerald; Kunst, Eike; Benson, Hannah; Sasse, Florenz; Siems, Karsten; Kirschning, Andreas

    2016-10-14

    The synthesis of the diterpene (+)-tonantzitlolone A and a series of derivatives is reported. The study includes the determination of their antiproliferative activities against selected cancer cell lines.

  5. Antioxidant and antiproliferative activities of Desmodium triflorum (L.) DC.

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    Lai, Shang-Chih; Ho, Yu-Ling; Huang, Shun-Chieh; Huang, Tai-Hung; Lai, Zhen-Rung; Wu, Chi-Rei; Lian, Kuo-Yuan; Chang, Yuan-Shiun

    2010-01-01

    This study evaluated the antioxidant and antiproliferative activities of the crude extract and fractions of Desmodium triflorum (L.) DC. The total phenolic content, 1,1-diphenyl-2- picrylhydrazyl hydrate (DPPH) free radical scavenging activity, trolox equivalent antioxidant capacity (TEAC), reducing power, total flavonoid content of D. triflorum were evaluated for the exploration of its antioxidant activities. Furthermore, its antiproliferative activities were investigated through the MTT method. It was compared with the antioxidant capacities of known antioxidants, including catechin, alpha-tocopherol, trolox and ascorbic acid. Among all fractions, ethyl acetate fraction was the most active in scavenging DPPH and TEAC radicals, of which 0.4 mg was equivalent to 186.6 +/- 2.5 microg and 82.5 +/- 2.1 microg of alpha-tocopherol and trolox respectively. The total phenolic and flavonoid contents of the crude extract were equivalent to 36.60 +/- 0.1 mg catechin and 45.6 +/- 0.6 mg rutin per gram respectively. In the reducing power assay, 1.25 mg of crude extract was similar to 61.2 +/- 0.3 microg of ascorbic acid. For the assessment of the safety and toxicity of D. triflorum, LD(50) of the crude extract was greater than 10 g/kg when administered to mice through gastric intubation. The above experimental data indicated that D. triflorum was a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds.

  6. Antioxidant, Antimicrobial and Antiproliferative Activities of Five Lichen Species

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    Snežana Marković

    2011-08-01

    Full Text Available The antioxidative, antimicrobial and antiproliferative potentials of the methanol extracts of the lichen species Parmelia sulcata, Flavoparmelia caperata, Evernia prunastri, Hypogymnia physodes and Cladonia foliacea were evaluated. The total phenolic content of the tested extracts varied from 78.12 to 141.59 mg of gallic acid equivalent (GA/g of extract and the total flavonoid content from 20.14 to 44.43 mg of rutin equivalent (Ru/g of extract. The antioxidant capacities of the lichen extracts were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH radicals scavenging. Hypogymnia physodes with the highest phenolic content showed the strongest DPPH radical scavenging effect. Further, the antimicrobial potential of the lichen extracts was determined by a microdilution method on 29 microorganisms, including 15 strains of bacteria, 10 species of filamentous fungi and 4 yeast species. A high antimicrobial activity of all the tested extracts was observed with more potent inhibitory effects on the growth of Gram (+ bacteria. The highest antimicrobial activity among lichens was demonstrated by Hypogymnia physodes and Cladonia foliacea. Finally, the antiproliferative activity of the lichen extracts was explored on the colon cancer adenocarcinoma cell line HCT-116 by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide viability assay and acridine orange/ethidium bromide staining. The methanol extracts of Hypogymnia physodes and Cladonia foliacea showed a better cytotoxic activity than the other extracts. All lichen species showed the ability to induce apoptosis of HCT-116 cells.

  7. Trigona laeviceps propolis from Thailand: antimicrobial, antiproliferative and cytotoxic activities.

    Science.gov (United States)

    Umthong, Supawadee; Puthong, Songchan; Chanchao, Chanpen

    2009-01-01

    Propolis is one of the natural bee products which has long been used as a crude preventative and prophylactic medicine, and has been reported to possess antibacterial, antiviral, anti-inflammatory, antioxidative and anticancer properties. Propolis of the stingless bee, Trigona laeviceps, was extracted by water or methanol at 35% (w/v) yielding a crude water or a methanolic extract at 60 and 80 mg/ml, respectively, which is 17.1 and 22.9% (w/w) of the total propolis, respectively. The antimicrobial activity of both crude extracts was assayed on four selected pathogenic microbes by using the agar well diffusion method. The results suggested that both water and methanolic crude extracts have some antimicrobial activities, water extract has greater antimicrobial activity than methanolic extract. The relative order of sensitivity of the four microbes were, however, the same between the two extracts from the most to least sensitive, S. aureus > E. coli > C. albicans > A. niger, with indeed no observed growth inhibition of A. niger at all. Antiproliferative and cytotoxic affects were tested on the colon carcinoma cell line, SW620, using the three parameters: (1) MTT assay; (2) cell morphology; and (3) the fragmentation of genomic DNA. The water extract of propolis showed a higher antiproliferative activity than that of methanolic extract to SW620 cells, additionally both appeared to cause cell death by necrosis.

  8. Antioxidant, antimicrobial and antiproliferative activities of five lichen species.

    Science.gov (United States)

    Mitrović, Tatjana; Stamenković, Slaviša; Cvetković, Vladimir; Tošić, Svetlana; Stanković, Milan; Radojević, Ivana; Stefanović, Olgica; Comić, Ljiljana; Dačić, Dragana; Curčić, Milena; Marković, Snežana

    2011-01-01

    The antioxidative, antimicrobial and antiproliferative potentials of the methanol extracts of the lichen species Parmelia sulcata, Flavoparmelia caperata, Evernia prunastri, Hypogymnia physodes and Cladonia foliacea were evaluated. The total phenolic content of the tested extracts varied from 78.12 to 141.59 mg of gallic acid equivalent (GA)/g of extract and the total flavonoid content from 20.14 to 44.43 mg of rutin equivalent (Ru)/g of extract. The antioxidant capacities of the lichen extracts were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals scavenging. Hypogymnia physodes with the highest phenolic content showed the strongest DPPH radical scavenging effect. Further, the antimicrobial potential of the lichen extracts was determined by a microdilution method on 29 microorganisms, including 15 strains of bacteria, 10 species of filamentous fungi and 4 yeast species. A high antimicrobial activity of all the tested extracts was observed with more potent inhibitory effects on the growth of Gram (+) bacteria. The highest antimicrobial activity among lichens was demonstrated by Hypogymnia physodes and Cladonia foliacea. Finally, the antiproliferative activity of the lichen extracts was explored on the colon cancer adenocarcinoma cell line HCT-116 by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) viability assay and acridine orange/ethidium bromide staining. The methanol extracts of Hypogymnia physodes and Cladonia foliacea showed a better cytotoxic activity than the other extracts. All lichen species showed the ability to induce apoptosis of HCT-116 cells.

  9. C-Glycosidic Genistein Conjugates and Their Antiproliferative Activity

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    Aleksandra Rusin

    2013-01-01

    Full Text Available This paper presents our attempt to investigate scopes and the limitations of olefin cross-metathesis (CM reaction in the synthesis of complex C-glycosides of genistein and evaluation of their antiproliferative activities. Novel genistein glycoconjugates were synthesized with the utility of CM reaction initiated by first and second generation of Grubbs catalysts. The relative reactivity of utilized olefins, based on categories proposed by Grubbs, was estimated. In vitro experiments in cancer cell lines showed that the selected derivatives (3a and 3f exhibited higher antiproliferative potential than the parent compound, genistein, and were able to block the cell cycle in the G2/M phase. The observed mechanism of action of C-glycosidic derivatives was similar to the activity of their O-glycosidic counterparts. These compounds were stable in culture medium. The obtained results show that our approach to genistein modification with application of cross-metathesis reaction allowed to obtain stable glycoconjugates with improved anticancer potential, compared to the parent isoflavone.

  10. Synthesis and antiproliferative activity of new bioconjugates of Salinomycin with amino acid esters.

    Science.gov (United States)

    Antoszczak, Michał; Sobusiak, Maria; Maj, Ewa; Wietrzyk, Joanna; Huczyński, Adam

    2015-09-01

    New Salinomycin (SAL) bioconjugates with amino acid methyl esters were obtained and their antiproliferative activity against cancer cell lines including drug-resistant ones was studied. New compounds exhibit antiproliferative activity towards leukemia and doxorubicin-resistant colon adenocarcinoma cell line and are more effective and less toxic than the commonly currently used anticancer drugs.

  11. Analysis of Flavonoids in Rhamnus davurica and Its Antiproliferative Activities

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    Guilin Chen

    2016-09-01

    Full Text Available Rhamnus davurica Pall. (R. davurica has been used as a traditional medicinal herb for many years in China and abroad. It has been well documented as a rich source of flavonoids with diversified structures, which in turn results in far-ranging biological activities, such as anti-inflammation, anticancer, antibacterial and antioxidant activities. In order to further correlate their anticancer potentials with the phytochemical components, the fingerprint profile of R. davurica herb from Dongbei was firstly investigated using HPLC-ESI-MS/MS. Thirty two peaks were detected and identified, 14 of which were found in R. davurica for the first time in this work. Furthermore, a total of 23 peaks were resolved as flavonoids, which are the major components found in R. davurica. Meanwhile, the antiproliferative activities against human cancer cells of HT-29 and SGC-7901 in vitro exhibited distinct inhibitory effects with IC50 values at 24.96 ± 0.74 and 89.53 ± 4.11 μg/mL, respectively. Finally, the general toxicity against L-O2 cells displayed a much higher IC50 at 229.19 ± 8.52 μg/mL, which suggested very low or no toxicity on hepatic cell viability. The current study revealed for the first time the correlations between the flavonoids of R. davurica with their antiproliferative activities, which indicated that the fingerprint profile of flavonoids and their anticancer activities could provide valuable information on the quality control for herbal medicines and their derived natural remedies from this valuable medicinal plant.

  12. Polyphenols with Anti-Proliferative Activities from Penthorum Chinense Pursh

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    Doudou Huang

    2014-07-01

    Full Text Available Two new polyphenols, penthorumin C (1 and 2,6-dihydroxyacetophenone-4-O- [4ꞌ,6ꞌ-(S-hexahydroxydiphenoyl]-β-D-glucose (2, along with four known polyphenolic acids, pinocembrin-7-O-[4ꞌꞌ,6ꞌꞌ-hexahydroxydiphenoyl]-β-D-glucose(3, pinocembrin-7-O-[3ꞌꞌ-O- galloyl- 4ꞌꞌ,6ꞌꞌ-hexahydroxydiphenoyl]-β-D-glucose (4, thonningianin A (5, and thonningianin B (6 were isolated from Penthourm chinense. All compounds were evaluated for their anti-proliferative activity in HSC-T6 cells, and 2 and 5 showed significant activity, with IC50 values of 12.7 and 19.2 μM, respectively.

  13. Synthesis and antiproliferative activity of glutamic acid-based dipeptides.

    Science.gov (United States)

    Silveira-Dorta, Gastón; Martín, Víctor S; Padrón, José M

    2015-08-01

    A small and focused library of 22 dipeptides derived from N,N-dibenzylglutamic acid α- and γ-benzyl esters was prepared in a straightforward manner. The evaluation of the antiproliferative activity in the human solid tumor cell lines HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast), and WiDr (colon) provided γ-glutamyl methionine (GI50 = 6.0-41 μM) and α-glutamyl proline (GI50 = 7.5-18 μM) as lead compounds. In particular, glutamyl serine and glutamyl proline dipeptides were more active in the resistant cancer cell line WiDr than the conventional anticancer drugs cisplatin and etoposide. Glutamyl tryptophan dipeptides did not affect cell growth of HBL-100, while in T-47D cells, proliferation was inhibited. This result might be attributed to the inhibition of the ATB(0,+) transporter.

  14. Antiproliferative Activity of Hamigerone and Radicinol Isolated from Bipolaris papendorfii

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    Periyasamy Giridharan

    2014-01-01

    Full Text Available Secondary metabolites from fungi organisms have extensive past and present use in the treatment of many diseases and serve as compounds of interest both in their natural form and as templates for synthetic modification. Through high throughput screening (HTS and bioassay-guided isolation, we isolated two bioactive compounds hamigerone (1 and radicinol (2. These compounds were isolated from fungus Bipolaris papendorfii, isolated from the rice fields of Dera, Himachal Pradesh, India. The structures of the compounds were established on the basis of spectroscopic data, namely, NMR (1H, 13C, mass, and UV. Both compounds were found to be antiproliferative against different cancer cells. Furthermore we have also noted that both compounds showed increase in apoptosis by favorably modulating both tumor suppressor protein (p53 and antiapoptic protein (BCL-2, and in turn increase caspase-3 expression in cancer cells. This is the first report of these compounds from fungus Bipolaris papendorfii and their anticancer activity.

  15. Separation and purification and in vitro anti-proliferative activity of leukemia cell K562 of Galium aparine L. petroleum

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    Guoqing Shi

    2016-05-01

    Full Text Available To explore material basis of in vitro anti-proliferative activity of leukemia cell K562 of petroleum ether phase of product resulting from Galium aparine L. 60% ethanol extraction, the experiment adopts column chromatography combined with thin layer preparation, isolates and purifies petroleum ether, conducts structural identification of obtained single compound and applies MTT method for viability assay of in vitro anti-proliferative activity of leukemia cell K562. Experimental results show that G. aparine L. petroleum ether contains mainly β-sitosterol, daucosterol and dibutyl phthalate and other substances. Under experimental conditions, the three could inhibit the proliferation of leukemia cell K562 with dose-effect and time-effect relationship, of which dibutyl phthalate has strongest activity. Dibutyl phthalate with excellent activity, β-sitosterol with rich content and moderate effect should be the main contributor to its biological activity.

  16. Synthesis and antiproliferative activity of monocationic arylthiophene derivatives.

    Science.gov (United States)

    Ismail, Mohamed A; Youssef, Magdy M; Arafa, Reem K; Al-Shihry, Shar S; El-Sayed, Wael M

    2017-01-27

    Eleven compounds of substituted 4-(5-arylthiophen-2-yl)benzamidines 4a-k were synthesized from their corresponding mononitriles via treatment with lithium trimethylsilylamide and subsequent de-protection with ethanol/hydrogen chloride. In vitro antiproliferative activities of the new monocationic arylthiophenes were evaluated against 60 human cell lines at NCI, USA. This class of compounds displayed promising submicromolar antiproliferative activities with the most potent compound being 4i (GI50 and TGI of 0.20 and 0.37 μM, respectively). On the other hand, most of the tested compounds exhibited LC50 at concentrations much higher than those they had GI50 at; ∼10× (for 4b) up to 228× (for 4e) which indicates lower lethality and efficient growth inhibition. Cancer cell lines, HCC-2998 colon, SNB-75 CNS, MDA-MB-435 melanoma, and MCF-7 breast cancer were the most responsive, with GI50s of 0.156, 0.165, 0.163, and 0.168 μM, respectively. The p-chlorophenyl derivatives 4e and 4i discerned themselves with GI50 values at 0.36 and 0.20 μM, respectively, and LC50 values at ∼83 and 36 μM, respectively, but safe to RBCs at 1000 μM. The cytotoxic activity data of these compounds in two normal cell lines; WI38 and WISH proved that they are very safe on normal cells. The plausible mechanism of action of the tested monocations was examined by evaluating their antioxidant power, nuclease-like DNA degradation aptitude and tyrosine kinase (TK) inhibition activities. The tested monocations showed potent activity in all assays. Compounds 4e and 4i caused 88 and 98%, respectively, inhibition in TK activity at 1 μM and the IC50 for 4i was 13 nM. The tested monocations have selective anticancer activity without insulting normal cells most probably due to inhibition of the key enzyme TK at nanomolar concentrations.

  17. Copper Ion Attenuated the Antiproliferative Activity of Di-2-pyridylhydrazone Dithiocarbamate Derivative; However, There Was a Lack of Correlation between ROS Generation and Antiproliferative Activity.

    Science.gov (United States)

    Wang, Tingting; Fu, Yun; Huang, Tengfei; Liu, Youxun; Wu, Meihao; Yuan, Yanbin; Li, Shaoshan; Li, Changzheng

    2016-08-20

    The use of chelators for cancer treatment has been an alternative option. Dithiocarbamates have recently attracted considerable attention owning to their diverse biological activities; thus, the preparation of new dithiocarbamate derivatives with improved antitumor activity and selectivity as well as probing the underlying molecular mechanism are required. In this study, di-2-pyridylhydrazone dithiocarbamate S-propionic acid (DpdtpA) and its copper complex were prepared and characterized, and its antiproliferative activity was evaluated. The proliferation inhibition assay showed that DpdtpA exhibited excellent antiproliferative effect in hepatocellular carcinoma (IC50 = 1.3 ± 0.3 μM for HepG2, and 2.5 ± 0.6 μM for Bel-7402). However, in the presence of copper ion, the antiproliferative activity of DpdtpA was dramatically attenuated (20-30 fold) owing to the formation of copper chelate. A preliminarily mechanistic study revealed that reactive oxygen species (ROS) generation mediated the antiproliferative activity of DpdtpA, and accordingly induced apoptosis, DNA cleavage, and autophagy. Surprisingly, the cytotoxicity of DpdtpA copper complex (DpdtpA-Cu) was also involved in ROS generation; however, a paradoxical relation between cellular ROS level and cytotoxicity was observed. Further investigation indicated that DpdtpA could induce cell cycle arrest at the S phase; however, DpdtpA-Cu lacked this effect, which explained the difference in their antiproliferative activity.

  18. Copper Ion Attenuated the Antiproliferative Activity of Di-2-pyridylhydrazone Dithiocarbamate Derivative; However, There Was a Lack of Correlation between ROS Generation and Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Tingting Wang

    2016-08-01

    Full Text Available The use of chelators for cancer treatment has been an alternative option. Dithiocarbamates have recently attracted considerable attention owning to their diverse biological activities; thus, the preparation of new dithiocarbamate derivatives with improved antitumor activity and selectivity as well as probing the underlying molecular mechanism are required. In this study, di-2-pyridylhydrazone dithiocarbamate S-propionic acid (DpdtpA and its copper complex were prepared and characterized, and its antiproliferative activity was evaluated. The proliferation inhibition assay showed that DpdtpA exhibited excellent antiproliferative effect in hepatocellular carcinoma (IC50 = 1.3 ± 0.3 μM for HepG2, and 2.5 ± 0.6 μM for Bel-7402. However, in the presence of copper ion, the antiproliferative activity of DpdtpA was dramatically attenuated (20–30 fold owing to the formation of copper chelate. A preliminarily mechanistic study revealed that reactive oxygen species (ROS generation mediated the antiproliferative activity of DpdtpA, and accordingly induced apoptosis, DNA cleavage, and autophagy. Surprisingly, the cytotoxicity of DpdtpA copper complex (DpdtpA–Cu was also involved in ROS generation; however, a paradoxical relation between cellular ROS level and cytotoxicity was observed. Further investigation indicated that DpdtpA could induce cell cycle arrest at the S phase; however, DpdtpA–Cu lacked this effect, which explained the difference in their antiproliferative activity.

  19. Design, synthesis and antiproliferative activity studies of novel dithiocarbamate-chalcone derivates.

    Science.gov (United States)

    Fu, Dong-Jun; Zhang, Sai-Yang; Liu, Ying-Chao; Zhang, Li; Liu, Jun-Ju; Song, Jian; Zhao, Ruo-Han; Li, Feng; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-08-15

    A series of novel dithiocarbamate-chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds II2 and II5 exhibited the excellent growth inhibition against SK-N-SH with IC50 values of 2.03μM and 2.46μM, respectively. Further mechanism studies revealed that compound II2 could obviously inhibit the proliferation of SK-N-SH cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase.

  20. Antiproliferative and antibacterial activity of some glutarimide derivatives.

    Science.gov (United States)

    Popović-Djordjević, Jelena B; Klaus, Anita S; Žižak, Željko S; Matić, Ivana Z; Drakulić, Branko J

    2016-12-01

    Antiproliferative and antibacterial activities of nine glutarimide derivatives (1-9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9-27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6-8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10(-3 )mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.

  1. Anti-proliferative activity of Monensin and its tertiary amide derivatives.

    Science.gov (United States)

    Huczyński, Adam; Klejborowska, Greta; Antoszczak, Michał; Maj, Ewa; Wietrzyk, Joanna

    2015-10-15

    New tertiary amide derivatives of polyether ionophore Monensin A (MON) were synthesised and their anti-proliferative activity against cancer cell lines was studied. Very high activity (IC50=0.09 μM) and selectivity (SI=232) of MON against human biphenotypic myelomonocytic leukemia cell line (MV4-11) was demonstrated. The MON derivatives obtained exhibit interesting anti-proliferative activity, high selectivity index and also are able to break the drug-resistance of cancer cell line.

  2. Phytochemical Contents and Antioxidant and Antiproliferative Activities of Selected Black and White Sesame Seeds.

    Science.gov (United States)

    Zhou, Lin; Lin, Xiaohui; Abbasi, Arshad Mehmood; Zheng, Bisheng

    2016-01-01

    Sesame (Sesamum indicum L.) seeds are popular nutritional food but with limited knowledge about their antioxidant and antiproliferative activities of various varieties. Phytochemical profiles and antioxidant and antiproliferative activities of six varieties of sesame (Sesamum indicum L.) seeds were studied. Fenheizhi3 (black) cultivar exhibited the maximum contents of total phenolics and lignans and values of total oxygen radical absorbance capacity (ORAC) and antiproliferative activity (EC50) against HepG2 cells. Bound ORAC values showed strong associations with bound phenolics contents (r = 0.976, p sesame seeds generally depicted higher total phenolics compared to the three white varieties. The antioxidant (ORAC values) and antiproliferation activities of six sesame seeds were both associated with contents of bound phenolics (r > 0.8, p < 0.05). Interestingly, nonlignan components in bound phenolics contributed to the antioxidant and antiproliferative activities. This study suggested that Fenheizhi3 variety is superior to the other five varieties as antioxidant supplements.

  3. Mycelial fermentation characteristics and antiproliferative activity of Phellinus vaninii Ljup

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    Wei Hu

    2014-01-01

    Full Text Available Background: The mycelial fermentation of higher fungi were investigated to posses various bioactivities. Materials and Methods: The mycelial growth and pellet morphology in a 5-L bioreactor were investigated. The mycelial broth containing biomass and extracellular products harvested from the fermentor was tested for antiproliferative activity of colon cancer LoVo cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-Diphenyltetrazolium Bromide assay. Results: The maximum mycelial concentration in a 5-L bioreactor was 12.5 g/L after 8 days cultivation. Further investigation in the mycelial pellets during the fermentation period revealed that the mean diameter of the pellet morphology was positively correlated with mycelial biomass (R2 = 0.82, P < 0.05 and broth viscosity (R2 = 0.90, P < 0.01, significantly. The ethyl acetate extract showed the most significant effects, increasing the inhibition rate up to 87.5% after 48 h at concentration of 1000 μg/mL. Conclusion: The results demonstrated the feasibility of P. vaninii Ljup mycelial fermentation for large-scale production of bioactive and medicinal compounds.

  4. Antioxidant, antiproliferative and antimicrobial activity of freeze-dried raspberry

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    Vulić Jelena J.

    2014-01-01

    Full Text Available The main chemical composition, i.e. the total content of bioactive compounds (phenolics 2209.86 ± 70.32 mg GAE/100g FDR, flavonoids 831.87 ± 12.61 mg R/100g FDR and anthocyanins 144.55 ± 0.39 mg CGE/100g FDR, in freeze-dried raspberry (FDR was evaluated spectrophotometrically. Vitamin C content was determined by HPLC analysis (88.81 ± 4.38 mg vit C/100g FDR. Antioxidant activities of FDR extract were evaluated spectrophotometrically on stable 2,2-diphenyl-1-picrylhydrazyl (DPPH free radicals and by electron spin resonance spectroscopy (ESR method on hydroxyl radicals (•OH. EC50 values were evaluated. EC50 DPPH• was 0.127 ± 0.013 mg/ml, while EC50 •OH was 1.366 ± 0.026 mg/ml. Antiproliferative activity of the FDR extract was evaluated in vitro in three human cell lines by colorimetric sulphorhodamine B (SRB assay. The most pronounced effects were obtained in the breast adenocarcinoma cell line (MCF7. EC50 value was 395.07 ± 96.38 μg/ml. Antimicrobial activity was determined by disk diffusion method. The FDR extract produced a clear inhibition zone (without visible colonies only toward Staphylococcus aureus. The minimal inhibitory (MIC and minimal bactericidal (MBC concentrations of FDR extract were evaluated. The values MIC were in the range of 4.7 - 100 mg/ml, and of MBC in the range of 6.3 - > 100 mg/ml.[ Projekat Ministarstva nauke Republike Srbije, br. TR 31044

  5. Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.

    Science.gov (United States)

    Goldeman, Waldemar; Nasulewicz-Goldeman, Anna

    2014-08-01

    A series of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids was synthesized in the reaction of triethylphosphite with isonitriles followed by hydrolysis or dealkylation. The in vitro anti-proliferative effect of all synthesized tetraphosphonic acids against MCF-7 breast cancer cells, J774E macrophages and HL-60 promyelocytic leukemia cells was determined. Three aromatic derivatives (5a, 5f and 5j) showed a similar or higher anti-proliferative activity than zoledronic acid.

  6. Metabolites from roots of Colubrina greggii var. yucatanensis and evaluation of their antiprotozoan, cytotoxic and antiproliferative activities

    Energy Technology Data Exchange (ETDEWEB)

    Dominguez-Carmona, Dafne B.; Escalante-Erosa, Fabiola; Garcia-Sosa, Karlina; Pena-Rodriguez, Luis M., E-mail: lmanuel@cicy.m [Centro de Investigacion Cientifica de Yucatan (Mexico). Unidad de Biotecnologia; Ruiz-Pinell, Grace; Gutierrez-Yapu, David; Gimenez-Turba, Alberto [Universidad Mayor de San Andres, La Paz (Bolivia, Plurinational State of). Inst. de Investigaciones Farmaco-Bioquimicas; Chan-Bacab, Manuel J. [Universidad Autonoma de Campeche (Mexico). Dept. de Microbiologia Ambiental y Biotecnologia; Moo-Puc, Rosa E. [Centro Medico Ignacio Garcia Tellez, Col. Industrial, Merida, Yucatan (Mexico). Unidad de Investigacion Medica Yucatan y Unidad Medica de Alta Especialidad; Veitch, Nigel C. [Jodrell Laboratory, Richmond, Surrey (United Kingdom)

    2011-07-01

    Purification of the root extract of Colubrina greggii var. yucatanensis resulted in the isolation and identification of 3-O-acetyl ceanothic acid as a new natural ceanothane triterpene, together with the known metabolites ceanothic acid, cenothenic acid, betulinic acid, discarine B and chrysophanein. The natural products and the semisynthetic esters acetyl dimethyl ceanothate, dimethyl ceanothate and chrysophanein peracetate showed moderate to low leishmanicidal and trypanocidal activities. None of the metabolites showed cytotoxic or antiproliferative effects. The results also suggested that betulinic acid contributes to the antiplasmodial activity originally detected in the crude root extract of C. greggii var. yucatanensis. (author)

  7. Evaluation of Abelmoschus moschatus extracts for antioxidant, free radical scavenging, antimicrobial and antiproliferative activities using in vitro assays

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    Qureshi Insaf A

    2011-08-01

    -IV have demonstrated potential antiproliferative activity against two human cell lines - Colorectal adenocarcinoma (COLO-205 and retinoblastoma (Y79. Conclusion The seed and leaf extracts of A. moschatus possess significant antioxidant activity and could serve as free radical inhibitors or scavenger, or substitute, probably as primary antioxidants. The plant possesses moderate antibacterial activity against bacterial strains used in this study. Hydroalcoholic seed and leaf extracts also exhibited antiproliferative activity against two human cancer cell lines. A. moschatus may therefore, be a good candidate for functional foods as well as pharmaceutics.

  8. Evaluation of Abelmoschus moschatus extracts for antioxidant, free radical scavenging, antimicrobial and antiproliferative activities using in vitro assays.

    Science.gov (United States)

    Gul, Mir Z; Bhakshu, Lepakshi M; Ahmad, Farhan; Kondapi, Anand K; Qureshi, Insaf A; Ghazi, Irfan A

    2011-08-17

    activity against two human cell lines - Colorectal adenocarcinoma (COLO-205) and retinoblastoma (Y79). The seed and leaf extracts of A. moschatus possess significant antioxidant activity and could serve as free radical inhibitors or scavenger, or substitute, probably as primary antioxidants. The plant possesses moderate antibacterial activity against bacterial strains used in this study. Hydroalcoholic seed and leaf extracts also exhibited antiproliferative activity against two human cancer cell lines. A. moschatus may therefore, be a good candidate for functional foods as well as pharmaceutics.

  9. Antiproliferative activity of methanol extracts of four species of Croton on different human cell lines

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    Jóice P. Savietto

    2013-08-01

    Full Text Available Several species of Croton have been described with biological activities, mainly due to diterpenes, alkaloids and/or other secondary metabolites. These activities account for the traditional use of Croton species to treat certain diseases in South America, Asia and Western Africa. The crude methanol extracts obtained from leaves and steam bark of Croton dichrous Müll. Arg., C. erythroxyloides Baill., C. myrianthus Müll. Arg. and C. splendidus Mart. ex Colla were tested for antiproliferative activity against ten human cancer cell lines. Chemical analyses of all extracts were carried out by GC/MS and HPLC/MS/MS. The leaf extract obtained from C. erythroxyloides showed potent activity against PC-3 (prostate and OVCAR-3 (ovary cell lines. Lupeol is suggested to be involved in such activity. Tiliroside, an acyl-glycosilated flavonoid ubiquitous in all tested extracts, seems to play an important role in the observed moderate activity of most extracts against the leukemia K562 cell lineage.

  10. In vitro antioxidant, antimutagenic and antiproliferative activities of collagen hydrolysates of jumbo squid (Dosidicus gigas byproducts

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    Guadalupe Miroslava Suárez-Jiménez

    2015-09-01

    Full Text Available AbstractHydrolysates from two different jumbo squid byproducts (fins and arms, produced by trypsin and protease type XIV were compared on the basis of their antioxidant (DPPH and ABTS radical scavenging assays, antimutagenic (Ames test and antiproliferative (Transformation cell proliferation in M12.C3F6 murine cells activities. Jumbo squid arms had higher content of collagen than fins, and their hydrolysates had the highest antioxidant activity. Also, jumbo squid arm-derived collagen hydrolyzed with protease XIV showed the highest antimutagenic activity. The four hydrolysates obtained showed low antiproliferative activity, however they are susceptible for further studies to be applied as food additives.

  11. Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives.

    Science.gov (United States)

    Guimarães, Keller G; de Freitas, Rossimiriam P; Ruiz, Ana L T G; Fiorito, Giovanna F; de Carvalho, João E; da Cunha, Elaine F F; Ramalho, Teodorico C; Alves, Rosemeire B

    2016-03-23

    A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 μg mL(-1)). This compound represents a promising matrix for developing new antiproliferative agents.

  12. Design, synthesis and antiproliferative activities of diaryl urea derivatives bearing N-acylhydrazone moiety

    Institute of Scientific and Technical Information of China (English)

    Bei Zhang; Yan Fang Zhao; Xin Zhai; Wei Jie Fan; Jun Ling Ren; Chun Fu Wu; Ping Gong

    2012-01-01

    A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized.All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line (HL-60),human lung adenocarcinoma epithelial cell hne (A549) and human breast cancer cell line (MDA-MB-231) in vitro by standard MTT assay.The pharmacological results indicated that some compounds exhibited promising antitumor activities.Compound lj showed the most potent antiproliferative activity against the tested three cell lines with IC50 values of 0.13 μmol/L,0.7 μ mol/L and 0.5 μmol/L,respectively.

  13. Triterpenoids isolated from apple peels have potent antiproliferative activity and may be partially responsible for apple's anticancer activity.

    Science.gov (United States)

    He, Xiangjiu; Liu, Rui Hai

    2007-05-30

    Bioactivity-guided fractionation of apple peels was used to determine the chemical identity of bioactive constituents. Thirteen triterpenoids were isolated, and their chemical structures were identified. Antiproliferative activities of the triterpenoids against human HepG2 liver cancer cells, MCF-7 breast cancer cells, and Caco-2 colon cancer cells were evaluated. Most of the triterpenoids showed high potential anticancer activities against the three human cancer cell lines. Among the compounds isolated, 2alpha-hydroxyursolic acid, 2alpha-hydroxy-3beta-{[(2E)-3-phenyl-1-oxo-2-propenyl]oxy}olean-12-en-28-oic acid, and 3beta-trans-p-coumaroyloxy-2alpha-hydroxyolean-12-en-28-oic acid showed higher antiproliferative activity toward HepG2 cancer cells. Ursolic acid, 2alpha-hydroxyursolic acid, and 3beta-trans-p-coumaroyloxy-2alpha-hydroxyolean-12-en-28-oic acid exhibited higher antiproliferative activity against MCF-7 cancer cells. All triterpenoids tested showed antiproliferative activity against Caco-2 cancer cells, especially 2alpha-hydroxyursolic acid, maslinic acid, 2alpha-hydroxy-3beta-{[(2E)-3-phenyl-1-oxo-2-propenyl]oxy}olean-12-en-28-oic acid, and 3beta-trans-p-coumaroyloxy-2alpha-hydroxyolean-12-en-28-oic acid, which displayed much higher antiproliferative activities. These results showed the triterpenoids isolated from apple peels have potent antiproliferative activity and may be partially responsible for the anticancer activities of whole apples.

  14. Antiproliferative activity of plant extracts used against cancer in traditional medicine.

    Science.gov (United States)

    Talib, Wamidh H; Mahasneh, Adel M

    2010-01-01

    Forty four extracts from sixteen plants used traditionally as anticancer agents were evaluated in vitro for their antiproliferative activity against Hep-2, MCF-7, and Vero cell lines. Plants were fractionated using ethanol, methanol, chloroform, n-hexane, distilled water, and butanol. The antiproliferative activity was measured by MTT assay. TLC was used to identify active fractions. The apoptotic activity of active fractions was determined using TUNEL colorimetric assay. 20 of these extracts demonstrated significant antiproliferative activity against one or more of the cell lines. These extracts were prepared from Ononis hirta, Inula viscosa, Salvia pinardi, Verbascum sinaiticum and Ononis sicula. Methanol fractions of Ononis hirta (aerial parts) and Inula viscosa (flowers) were the most active fractions against MCF-7 cells with IC(50) of 27.96 and 15.78 Îg/ml respectively and they were less toxic against other cell lines. Other extracts showed lower activity against cancer cell lines. TLC analysis showed the presence of flavonoids and terpenoids in active plants while alkaloids were detected in Ononis hirta (aerial parts) extracts. Ononis hirta (aerial parts) and Inula viscosa (flowers) extracts exerted their antiproliferative activity by inducing apoptosis in cancer cell lines. Further studies are necessary for detailed chemical characterization and more extensive biological evaluation of the most active ingredients.

  15. Two new diterpene derivatives from Euphorbia lunulata Bge and their anti-proliferative activities.

    Science.gov (United States)

    Liu, Chao; Liao, Zhi-xin; Liu, Shi-jun; Qu, Yan-bo; Wang, Heng-shan

    2014-07-01

    A new ent-abietane-type diterpene lactone (1) and a new jatrophane-type diterpenoid (2), together with twelve known compounds including three diterpenes (3-5), five triterpenes (6-10) and four sterides (11-14) were isolated from the ethanol extract of the whole plant of Euphorbia lunulata Bge. The structure of compounds 1 and 2 was elucidated on the basis of 1D and 2D NMR spectra and the HR-ESI-MS data. The structure of compound 2 was further analyzed by an X-ray crystallographic study. The in vitro anti-proliferative activities against MCF-7 and NCI-H460 cell lines for compounds 1-5 (diterpene) were evaluated. The results showed marked activity for compound 1 against the two cell lines with the IC50 values 19.5 (NCI-H460) and 18.6 (MCF-7) μM, while for cis-platinum (a positive cytotoxic control agent) 29.7 (NCI-H460) and 27.7 (MCF-7) μM. Compounds 2-5 exhibited moderate cytotoxic activities for the two cell lines with the IC50 values ranging from 32.1 to 58.2 μM.

  16. Antiproliferative Activity of Polyether Antibiotic--Cinchona Alkaloid Conjugates Obtained via Click Chemistry.

    Science.gov (United States)

    Skiera, Iwona; Antoszczak, Michał; Trynda, Justyna; Wietrzyk, Joanna; Boratyński, Przemysław; Kacprzak, Karol; Huczyński, Adam

    2015-10-01

    A series of eight new conjugates of salinomycin or monensin and Cinchona alkaloids were obtained by the Cu(I)-catalysed 1,3-dipolar Huisgen cycloaddition (click chemistry) of respective N-propargyl amides of salinomycin or monensin with four different Cinchona alkaloid derived azides. In vitro antiproliferative activity of these conjugates evaluated against three cancer cell lines (LoVo, LoVo/DX, HepG2) showed that four of the compounds exhibited high antiproliferative activity (IC50 below 3.00 μm) and appeared to be less toxic and more selective against normal cells than two standard anticancer drugs.

  17. Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts

    Science.gov (United States)

    2011-01-01

    Background Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts. Methods Hot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy. Results Higher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines. Conclusions The hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines. PMID:21429215

  18. Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts.

    Science.gov (United States)

    Predes, Fabricia S; Ruiz, Ana L T G; Carvalho, João E; Foglio, Mary A; Dolder, Heidi

    2011-03-23

    Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts. Hot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy. Higher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines. The hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines. © 2011 Predes et al; licensee BioMed Central Ltd.

  19. Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts

    Directory of Open Access Journals (Sweden)

    Carvalho João E

    2011-03-01

    Full Text Available Abstract Background Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts. Methods Hot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy. Results Higher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines. Conclusions The hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines.

  20. Total antioxidant and antiproliferative activities of twenty-four Vitis vinifera grapes

    Science.gov (United States)

    The phytochemical profiles of 24 Vitis vinifera grape cultivars, including total phenolics, total flavonoids, total antioxidant activity and antiproliferative activity, were determined. Total phenolic contents in the cultivars ranged from 95.3 to 686.5 mg of gallic acid equivalents/100 g FW, and to...

  1. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide

    OpenAIRE

    Lopez-Girona, A; Mendy, D; Ito, T.; Miller, K; A K Gandhi; Kang, J.(Yonsei University, Seoul, South Korea); Karasawa, S; Carmel, G; P Jackson; Abbasian, M; A Mahmoudi; Cathers, B; Rychak, E; Gaidarova, S; Chen, R.

    2012-01-01

    Thalidomide and the immunomodulatory drug, lenalidomide, are therapeutically active in hematological malignancies. The ubiquitously expressed E3 ligase protein cereblon (CRBN) has been identified as the primary teratogenic target of thalidomide. Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN–DNA damage binding protein-1 (DDB1) complexes. CRBN mediated antiproliferative activities of lenalidomid...

  2. In vitro antioxidant and antiproliferative activities of plants of the ethnopharmacopeia from northwest of Mexico

    Directory of Open Access Journals (Sweden)

    Jiménez-Estrada Manuel

    2013-01-01

    Full Text Available Abstract Background The aim of this study, is to investigate the in vitro antioxidant activity, the total phenols content, the flavonoids content and the antiproliferative activity of methanolic extracts of the plants: Krameria erecta, Struthanthus palmeri, Phoradendron californicum, Senna covesii and Stegnosperma halimifolium, used by different ethnic groups from northwestern Mexico in the treatment and cure of various diseases. Methods The in vitro antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH and Ferric Reducing/Antioxidant Power assay (FRAP, the total phenols content was measured by Folin–Ciocalteau assay, the flavonoids content by the AlCl3 colorimetric method and the antiproliferative activity (line cells HeLa, RAW 264.7, M12Ak.C3.F6 and L929 using MTT method. Results The K. erecta extract showed the higher radical scavenging activity (67.88%, antioxidant activity by FRAP (1.41 mg Trolox Eq, the highest total phenols content (598.51 mg Galic Acid Eq/g extract, the highest flavonoids content (3.80 mg Quercetin Eq/g extract and the greatest antiproliferative activity in a dose dependent manner against most Cell line evaluated. A positive correlation was found between the antioxidant activity and the flavonoids content. Conclusions This study is the first report on the antioxidant and antiproliferative activities of the five species evaluated. The results demostrate that there is a positive correlation between antioxidant activity and the flavonoids content, indicating that these type of polyphenols could be the major contributors to the observed antioxidant activity in the evaluated plant extracts. Of the extracts evaluated, that of Krameria erecta showed the greatest antioxidant and antiproliferative activities, a discovery that makes this species a promising candidate for future research.

  3. Biochemical characterization and antioxidant and antiproliferative activities of different Ganoderma collections.

    Science.gov (United States)

    Saltarelli, Roberta; Ceccaroli, Paola; Buffalini, Michele; Vallorani, Luciana; Casadei, Lucia; Zambonelli, Alessandra; Iotti, Mirco; Badalyan, Susanna; Stocchi, Vilberto

    2015-01-01

    The aim of this study was to conduct a molecular and biochemical characterization and to compare the antioxidant and antiproliferative activities of four Ganoderma isolates belonging to Ganoderma lucidum (Gl-4, Gl-5) and Ganoderma resinaceum (F-1, F-2) species. The molecular identification was performed by ITS and IGS sequence analyses and the biochemical characterization by enzymatic and proteomic approaches. The antioxidant activity of the ethanolic extracts was compared by three different methods and their flavonoid contents were also analyzed by high-performance liquid chromatography. The antiproliferative effect on U937 cells was determined by MTT assay. The studied mycelia differ both in the enzymatic activities and protein content. The highest content in total phenol and the highest antioxidant activity for DPPH free radical scavenging and chelating activity on Fe(2+) were observed with the Gl-4 isolate of G. lucidum. The presence of quercetin, rutin, myricetin, and morin as major flavonoids with effective antioxidant activity was detected. The ethanolic extracts from mycelia of G. lucidum isolates possess a substantial antiproliferative activity against U937 cells in contrast to G. resinaceum in which the antiproliferative effects were insignificant. This study provides a comparison between G. lucidum and G. resinaceum mycelial strains, and shows that G. resinaceum could be utilized to obtain several bioactive compounds.

  4. Comparative antitumor and anti-proliferative activities ofHippophae rhamnoidesL. leaves extracts

    Institute of Scientific and Technical Information of China (English)

    Javid Ali; Bashir Ahmad

    2015-01-01

    Objective:To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform andn-hexane extracts ofHippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens) with three different concentrations of test samples (10, 100 and 1 000 mg/L). Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8%) was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated inn-hexane extract. The difference in tumor and cell inhibition (%) may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions:Our finding showed thatHippophae rhamnoidesleaves are a potent natural source of antitumor and antiproliferative agent.

  5. Antiproliferative activity of hexane extract from Tunisian Cistus libanotis, Cistus monspeliensis and Cistus villosus

    Science.gov (United States)

    2013-01-01

    Background As a part of our investigation on Tunisian medicinal plants, we have carried out a phytochemical investigation of the hexane extracts from leaves of Cistus libanotis, C. villosus and C. monspeliensis, evualuating also their possible antiproliferative activity in vitro. Results The major compounds of hexane extracts were identified and quantified by GC-MS. The composition of the three species, although belonging to the same genus, is completely different. The antiproliferative activity was evaluated against murine monocyte/macrophages (J774.A1), human melanoma cells (A-375), and human breast cancer cells (MCF-7), showing major activity against the human melanoma cell line A-375. Conclusions The chemical composition of the hexane extracts from the three Cistus species can be useful in the chemosystematics of this complex genus. The preliminary antiproliferative activity against human melanoma cell line A-375 deserve further investigations in order to determine the compounds, or their combinations, which are the main responsible for the antiproliferative activity and its possible mechanism(s) of action. PMID:23497569

  6. Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives

    Directory of Open Access Journals (Sweden)

    Sinara Mônica Vitalino de Almeida

    2015-06-01

    Full Text Available In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z-2-(acridin-9-ylmethylene-N-phenylhydrazinecarbothioamide derivatives (3a–h were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 104 to 1.0 × 106 M−1 and quenching constants from −0.2 × 104 to 2.18 × 104 M−1 indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z-2-(acridin-9-ylmethylene-N- (4-chlorophenyl hydrazinecarbothioamide (3f, while the most active compound in antiproliferative assay was (Z-2-(acridin-9-ylmethylene-N-phenylhydrazinecarbothioamide (3a. There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.

  7. Role of the phenolic hydroxyl group in the biological activities of simplified analogue of aplysiatoxin with antiproliferative activity.

    Science.gov (United States)

    Yanagita, Ryo C; Kamachi, Hiroaki; Tanaka, Keisuke; Murakami, Akira; Nakagawa, Yu; Tokuda, Harukuni; Nagai, Hiroshi; Irie, Kazuhiro

    2010-10-15

    The 18-deoxy derivative (3) of a simplified analogue (1) of aplysiatoxin with antiproliferative activity was synthesized to examine the role of the phenolic hydroxyl group at position 18 in the biological activities of 1. Compound 3 as well as 1 showed significant affinity for protein kinase Cδ (PKCδ), and the antiproliferative activity of 3 was slightly higher than that of 1. However, the anti-tumor-promoting activity of 3 was less than that of 1 in vitro, suggesting that the phenolic hydroxyl group of 1 is necessary for the anti-tumor-promoting activity but not for the binding of PKCδ and antiproliferative activity. Moreover, PKC isozyme selectivity of 3 was similar to that of 1, suggesting non-PKC receptors for these compounds to play some roles in the anti-tumor-promoting activity of 1.

  8. Anti-proliferative activities of terpenoids isolated from Alisma orientalis and their structure-activity relationships.

    Science.gov (United States)

    Xu, Wen; Li, Ting; Qiu, Jian-Fang; Wu, Shui-Sheng; Huang, Ming-Qing; Lin, Li-Gen; Zhang, Qing-Wen; Chen, Xiu-Ping; Lu, Jin-Jian

    2015-01-01

    This study aimed to isolate terpenoids from Alisma orientalis (Sam.) Juzep. and elucidate their antiproliferative activities, as well as structure-activity relationships. Fourteen protostane-type triterpenoids were isolated from the rhizome of A. orientalis. Among these triterpenoids, alisol A (1), alisol A 24-acetate (2), alisol B (3), alisol B 23-acetate (4), and alisol G (8) presented inhibitory effects on cancer cell lines tested. Compounds 3 and 4 showed the highest potential; IC50 values for HepG2, MDA-MB-231, and MCF-7 cells were 16.28, 14.47, and 6.66 μM for 3 and 18.01, 15.97, and 13.56 μM for 4, respectively. Based on these results, we concluded that the degree of C-16 oxidation and the double bond between C-13 and C-17 may be significant in anti-proliferative activities. Further study showed that 3 and 4 effectively induced apoptosis, as confirmed by flow cytometry. Increased intracellular calcium concentration and endoplasmic reticulum stress were detected after treatment with 4 in HepG2 cells. Although compounds 1 and 2 induced minimal apoptosis, they evidently delayed the G2/M phase in HepG2 cells. Further study showed that 1-4 also enhanced LC3II expression, indicating autophagy is occured.

  9. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents.

    Science.gov (United States)

    Zhang, Sai-Yang; Fu, Dong-Jun; Yue, Xiao-Xin; Liu, Ying-Chao; Song, Jian; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-05-19

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma.

  10. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents

    Directory of Open Access Journals (Sweden)

    Sai-Yang Zhang

    2016-05-01

    Full Text Available A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma.

  11. Synthesis, antiproliferative and antimicrobial activity of new Mannich bases bearing 1,2,4-triazole moiety.

    Science.gov (United States)

    Popiołek, Łukasz; Rzymowska, Jolanta; Kosikowska, Urszula; Hordyjewska, Anna; Wujec, Monika; Malm, Anna

    2014-12-01

    Abstract This study presents the synthesis, antiproliferative and antimicrobial evaluation of a new series of Mannich base derivatives containing 1,2,4-triazole system. New compounds were prepared by the reaction of 4,5-disubstituted 1,2,4-triazole-3-thiones with formaldehyde and various amines. The structures of the prepared compounds were confirmed by means of (1)H NMR, (13)C NMR and elemental analyses. Twelve compounds were evaluated for their in vitro antiproliferative activities against six chosen cancer cell lines. All synthesized compounds were screened for their in vitro antimicrobial activity by using the agar dilution technique. For 17 potentially active compounds, their antibacterial activity was confirmed on the basis of MIC (minimal inhibitory concentration) by broth microdilution method using the reference Gram-positive and Gram-negative bacterial strains.

  12. Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines

    Directory of Open Access Journals (Sweden)

    Luis Sánchez-Sánchez

    2016-11-01

    Full Text Available Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells. These derivatives were synthesized from the steroidal sapogenin diosgenin in good yields. The in vitro assays show that the steroidal oximes show significant antiproliferative activity compared to the one observed for diosgenin. Cell proliferation, cell death, and the cytotoxic effects were determined in both cervical cancer cells and human lymphocytes. The cancer cells showed apoptotic morphology and an increased presence of active caspase-3, providing the notion of a death pathway in the cell. Significantly, the steroidal oximes did not exert a cytotoxic effect on lymphocytes.

  13. Synthesis and Antiproliferative Activity of Silybin Conjugates with Salinomycin and Monensin.

    Science.gov (United States)

    Antoszczak, Michał; Klejborowska, Greta; Kruszyk, Monika; Maj, Ewa; Wietrzyk, Joanna; Huczyński, Adam

    2015-12-01

    Aiming at development of multitarget drugs for the anticancer treatment, new silybin (SIL) conjugates with salinomycin (SAL) and monensin (MON) were synthesized, in mild esterification conditions, and their antiproliferative activity was studied. The conjugates obtained exhibit anticancer activity against HepG2, LoVo and LoVo/DX cancer cell lines. Moreover, MON-SIL conjugate exhibits higher anticancer potential and better selectivity than the corresponding SAL-SIL conjugate.

  14. In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao.

    Science.gov (United States)

    Baharum, Zainal; Akim, Abdah Md; Taufiq-Yap, Yun Hin; Hamid, Roslida Abdul; Kasran, Rosmin

    2014-11-10

    The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50) was 358.3±7.0 µg/mL and total phenolic content was 22.0±1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4%±1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50)=41.4±3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

  15. In Vitro Antioxidant and Antiproliferative Activities of Methanolic Plant Part Extracts of Theobroma cacao

    Directory of Open Access Journals (Sweden)

    Zainal Baharum

    2014-11-01

    Full Text Available The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH, thiobarbituric acid-reactive substances (TBARS, and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50 was 358.3 ± 7.0 µg/mL and total phenolic content was 22.0 ± 1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4% ± 1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50 = 41.4 ± 3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

  16. Antioxidant and antiproliferative activities of phenolics isolated from fruits of Himalayan yellow raspberry (Rubus ellipticus).

    Science.gov (United States)

    Saini, Ritu; Dangwal, Koushalya; Singh, Himani; Garg, Veena

    2014-11-01

    Yellow Himalayan raspberry, a wild edible fruit, was analyzed for phenolic contents, and antioxidant, antibacterial and antiproliferative activities. Phenolics were extracted using 80 % aqueous solvents containing methanol, acidic methanol, acetone and acidic acetone. Our analysis revealed that the acidic acetone extracts recovered the highest level of total phenolics (899 mg GAE/100 g FW) and flavonoids (433.5 mg CE/100 g FW). Free radical scavenging activities (DPPH, ABTS, superoxide and linoleate hydroperoxide radicals) and ferric reducing activity were highest in the acetone and acidic acetone extracts. No metal chelating or antibacterial activity was detected in any of the extracts. Acetone and methanol extracts showed potent antiproliferative activity against human cervical cancer cells (C33A) with an EC50 of inhibition at 5.04 and 4. 9 mg/ml fruit concentration respectively, while showing no cytotoxicity to normal PBMCs cells. Therefore, the present study concluded that the yellow Himalayan raspberry is a potent source of phytochemicals having super antioxidant and potent antiproliferative activities.

  17. New spiro-acridines: DNA interaction, antiproliferative activity and inhibition of human DNA topoisomerases.

    Science.gov (United States)

    Almeida, Sinara Mônica Vitalino de; Lafayette, Elizabeth Almeida; Silva, Willams Leal; Lima Serafim, Vanessa de; Menezes, Thais Meira; Neves, Jorge Luiz; Ruiz, Ana Lucia Tasca Gois; Carvalho, João Ernesto de; Moura, Ricardo Olímpio de; Beltrão, Eduardo Isidoro Carneiro; Carvalho Júnior, Luiz Bezerra de; Lima, Maria do Carmo Alves de

    2016-11-01

    Two new spiro-acridines were synthesized by introducing cyano-N-acylhydrazone between the acridine and phenyl rings followed by spontaneous cyclization. The final compounds (E)-1'-(benzylideneamino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-01) and (E)-1'-((4-methoxybenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-02) were evaluated for their interactions with calf thymus DNA, antiproliferative and human topoisomerase I and IIα inhibitory activities. Both compounds presented ability to bind DNA. The binding constant determined by UV-vis spectroscopy was found to be 10(4)M(-1). Antiproliferative assay demonstrated that AMTAC-01 and AMTAC-02 were most active against prostate and melanoma tumor cell lines, respectively. The compound did not present Topo I inhibitory activity. However, both derivatives displayed topoisomerase IIα inhibitory activity comparable to amsacrine, and AMTAC-02 was more potent than AMTAC-01 with methoxy substituent group on phenyl ring. This study demonstrates that the new derivatives are promising molecules with topoisomerase IIα inhibitory and antiproliferative activities.

  18. Qualitative and quantitative analysis of phenolics in Tetrastigma hemsleyanum and their antioxidant and antiproliferative activities.

    Science.gov (United States)

    Sun, Yong; Li, Hongyan; Hu, Jiangning; Li, Jing; Fan, Ya-wei; Liu, Xiao-ru; Deng, Ze-yuan

    2013-11-06

    The phenolic profiles of Tetrastigma hemsleyanum leaf extracts by different solvents (80% methanol, ethyl acetate and hexane) and their antioxidant and antiproliferative activities were investigated. Thirteen phenolic compounds (3-caffeoylquinic acid, 5-caffeoylquinic acid, 1-caffeoylquinic acid, 5-p-coumaroylquinic acid, isoorientin-2″-O-rhamnoside, isoorientin, orientin-2″-O-rhamnoside, orientin, 1-p-coumaroylquinic acid, vitexin-2″-O-rhamnoside, isovitexin-2″-O-rhamnoside, vitexin and isovitexin) were identified in T. hemsleyanum leaves for the first time, and six of them were quantified using a combination of LC-QTOF-MS and LC-QqQ-MS techniques. It was found that 80% methanol extract exhibited the highest antioxidant activities (DPPH, 3.32 mmol of Trolox/g DW; ABTS, 1.38 mmol of Trolox/g DW; FRAP, 1.85 mmol of FeSO4/g DW), while the hexane extract had the lowest (1.23, 0.43 and 0.13, respectively). Total phenolic contents (TPC) of various extracts of T. hemsleyanum leaves ranged from 28.95 to 275.71 mg of GAE/g DW. Also, total antioxidant activities as evaluated by ABTS, FRAP and DPPH assays were correlated well with TPC. In addition, 80% methanol extract provided antiproliferative activity on HepG2 cells (IC50 = 524 μg/mL). This paper provides a complete picture of phenolics in T. hemsleyanum leaves and relates them to their antioxidant and antiproliferative activities.

  19. Phytochemical screening and antioxidant, antimitotic, and antiproliferative activities of Trichodesma indicum shoot

    Directory of Open Access Journals (Sweden)

    Shweta S Saboo

    2014-01-01

    Full Text Available Background: Traditionally Trichodesma indicum has been used for its therapeutic effect in folk medicine that include anti-inflammatory, analgesic and anticancer properties. In this work, we validate the anticancer potential of the plant. Aims: To screen the shoot extracts T. indicum for their antimitotic and antiproliferative activities. Materials and Methods: The dried aerial parts of T. indicum were successively extracted with petroleum ether, successive chloroform extract (SCH, successive ethanol extract (SEE and water. The plant extracts were subjected to study of in vitro antioxidant activity using 2,2′- diphenyl-1-picrylhydrazyl, 2,2′- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radical inhibition systems. The extracts were also tested for their in vitro antimitotic activity in Allium cepa root and antiproliferative activity using the yeast model and five human cell lines (MCF-7, HOP-62, MOLT-4, HCT-15 and PRO. Result and Conclusion: The mitotic index for SCH and SEE was found to be 12.01 ± 1.34 and 12.99 ± 0.25 mg/mL, respectively. The IC 50 value in the antiproliferative assay was found to be 30.14-35.36 mg/mL for SCH and SEE respectively. Both SCH and SEE extracts showed significant antimitotic and antiproliferative activity when compared to the standard methothreaxate, vincreastine and adriamycin. Among the extracts, SEE showed strong inhibition against MCF-7 and MOLT-4 cell lines at concentration <30 μg/mL. Phytochemical analysis of extracts indicated the presence of β-sitosterol, gallic acid and catechin. Based on these results, it is concluded that T. indicum may be a good candidate for the treatment of a variety of cancer. Thus, its traditional use is validated.

  20. Isolation, Identification and Antiproliferative Activity of Triterpenes from the Genus Monotheca A. DC.

    Directory of Open Access Journals (Sweden)

    Shabnam Javed

    2016-05-01

    Full Text Available The Monotheca A. DC. is a monotypic genus of the family Sapotaceae, which is widely distributed in Afghanistan, Djbouti, Northern Somalia, Oman, Pakistan and Southern Ethiopia. North-west Pakistan is the main region where Monotheca buxifolia (Falc. A. DC., the only species of this genus, locally known as “Gurgura”, grows abundantly. It is an evergreen, fruit-producing medicinal tree. Bioassay-guided fractionation of the aerial parts of M. buxifolia afforded lupeol (1, lupeol acetate (2, betulin (3, oleanolic acid (4 andβ-amyrin (5 from the n-hexane and the chloroform fractions. This is the first report on the isolation, and identification of triterpenes (1-5 as the major compounds in the active fractions with antiproliferative property, and also on the antiproliferative activity of M. buxifolia extract and fractions against the human lung cancer cell line NCI-H460 in vitro.

  1. Kinetics Extraction Modelling and Antiproliferative Activity of Clinacanthus nutans Water Extract

    OpenAIRE

    Farah Nadiah Mohd Fazil; Nur Syarafina Mohd Azzimi; Badrul Hisham Yahaya; Nurulain Atikah Kamalaldin; Saiful Irwan Zubairi

    2016-01-01

    Clinacanthus nutans is widely grown in tropical Asia and locally known “belalai gajah” or Sabah snake grass. It has been used as a natural product to treat skin rashes, snake bites, lesion caused by herpes, diabetes, fever, and cancer. Therefore, the objectives of this research are to determine the maximum yield and time of exhaustive flavonoids extraction using Peleg's model and to evaluate potential of antiproliferative activity on human lung cancer cell (A549). The extraction process was c...

  2. Design, synthesis and antiproliferative activity of novel 2,7-disubstituted triazolo[1,5-a]pyrimidines

    Institute of Scientific and Technical Information of China (English)

    Xin Zhai; Nan Jiang; Ke Liang Zhang; Feng Bao; Ping Gong

    2009-01-01

    In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines (6-16). Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds (9-11 and 16) displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.

  3. Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

    Directory of Open Access Journals (Sweden)

    Mariano Walter Pertino

    2014-02-01

    Full Text Available Dehydroabietic acid (DHA is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid, and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol, four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM.

  4. Antioxidant, antimicrobial and antiproliferative activities of Anthemis palestina essential oil

    National Research Council Canada - National Science Library

    Bardaweel, Sanaa K; Tawaha, Khaled A; Hudaib, Mohammad M

    2014-01-01

    .... The antioxidant activity of the hydrodistilled oil was characterized using various in vitro model systems such as DPPH, ferric-reducing antioxidant power and hydroxyl radical scavenging activity...

  5. Synthesis and Promising in Vitro Antiproliferative Activity of Sulfones of a 5-Nitrothiazole Series

    Directory of Open Access Journals (Sweden)

    Nadine Azas

    2012-12-01

    Full Text Available  The synthesis in water of new sulfone derivatives under microwave irradiation is described. This eco-friendly process leads to the expected products in good yields by reaction of various substituted sulfinates (commercially available or obtained by reduction of the corresponding sulfonyl chlorides with 4-chloromethyl-2-methyl-5-nitro-1,3-thiazole. In order to evaluate the antiproliferative effect of these compounds, several sulfone derivatives are also dichlorinated on the Cα next to the sulfonyl group. An evaluation on different cancer cell lines reveals promising selective in vitro antiproliferative activity toward HepG2 human cell lines by dihydrogenated sulfones, suggesting further research should be to explore their anticancer potential in the treatment of liver cancer.

  6. Uncommon Trimethoxylated Flavonol Obtained from Rubus rosaefolius Leaves and Its Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Marcel Petreanu

    2015-01-01

    Full Text Available This study shows the evaluation the antiproliferative effect of the extract, fractions, and uncommon compounds isolated from R. rosaefolius leaves. The compounds were identified by conventional spectroscopic methods such as NMR-H1 and C13 and identified as 5,7-dihydroxy-6,8,4′-trimethoxyflavonol (1, 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone (2, and tormentic acid (3. Both hexane and dichloromethane fractions showed selectivity for multidrug-resistant ovary cancer cell line (NCI-ADR/RES with total growth inhibition values of 11.1 and 12.6 μg/ml, respectively. Compound 1 also showed selective activity against the same cell line (18.8 μg/ml; however, it was especially effective against glioma cells (2.8 μg/ml, suggesting that this compound may be involved with the in vitro antiproliferative action.

  7. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    Science.gov (United States)

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

  8. Chemical Composition, Antioxidant, Anti-Inflammatory, and Antiproliferative Activities of the Plant Lebanese Crataegus Azarolus L.

    Science.gov (United States)

    Kallassy, Hany; Fayyad-Kazan, Mohammad; Makki, Rawan; El-Makhour, Yolla; Hamade, Eva; Rammal, Hasan; Leger, David Y; Sol, Vincent; Fayyad-Kazan, Hussein; Liagre, Bertrand; Badran, Bassam

    2017-08-03

    BACKGROUND In the present study, phytochemical screening, antioxidant, anti-inflammatory, and antiproliferative capacities of 3 extracts from leaves of Lebanese Crataegus azarolus L. were evaluated. MATERIAL AND METHODS Fresh leaves were dissolved in 3 different solvents: distilled water, ethanol, and methanol. The chemical composition was determined using high-performance liquid chromatography (HPLC) and the content of essential oil of this plant was examined by gas chromatography (GC) coupled with mass spectrometry (MS). The antioxidant potential was evaluated using DPPH radical scavenging and Fe2+ chelating activity assays. Anti-inflammatory effect was investigated by measuring the secreted amounts of the proinflammatory mediator PGE2 using ELISA technique, as well as by assaying the mRNA levels of the proinflammatory cytokines (IL-α, IL-β, and Il-6), chemokines (CCL3 and CCL4) and inflammation-sensitive COX2 and iNOS enzymes using quantitative real-time PCR (qRT-PCR). The antiproliferative effect was evaluated using the XTT viability assay. RESULTS The obtained results show that alcohol (methanol and ethanol) extracts were rich in bioactive molecules with medical relevance and exerted substantial antioxidant, anti-inflammatory, and antiproliferative capacities. On the other hand, aqueous extract contained fewer chemical components and exhibited less therapeutic efficiency. CONCLUSIONS Our observations indicate that Crataegus azarolus L. could be used for treating diseases related to oxidative stress, inflammatory reactions, and uncontrolled cell growth.

  9. Antiproliferative Activities of Water Infusions from Leaves of Five Cornus L. Species

    Directory of Open Access Journals (Sweden)

    Vladimír Forman

    2015-12-01

    Full Text Available Cornaceae plants are known for their edible berries, and their leaves are used as tea. In the present study aqueous leaf extracts from Cornus mas (CM, C. alba (CA, C. flaviramea (CF, C. kousa (CK, and C. officinalis (CO were tested for their antiproliferative activity in human breast cancer cells (MCF-7. Dose- (50–750 µg/mL and time (24, 48, 72 h-dependent antiproliferative effects were measured by WST-1, and correlated with the content of flavonoids (FL, total hydroxycinnamic derivatives (THD, total polyphenols (TP and tannins (T. Extracts induced time dependent decreases in cell survival; CA, CO and CM were the most effective (11.2%, 10.3% and 11.1%, after 72 h. The ED50 (effective dose values were similar for all extracts and times tested. The THD and TP were identical in all samples, while a two-fold higher T content was present in CK and CO, and of FL in CF. The maximal effects (% of surviving cells negatively correlated with the T and TP levels, and positively with FL and THD. The results demonstrate the significant antiproliferative effects of the tested water extracts in MCF-7 cells, in which CA, CO and CM are the most effective; and the effectiveness is related to the T and TP contents.

  10. Kinetics Extraction Modelling and Antiproliferative Activity of Clinacanthus nutans Water Extract.

    Science.gov (United States)

    Fazil, Farah Nadiah Mohd; Azzimi, Nur Syarafina Mohd; Yahaya, Badrul Hisham; Kamalaldin, Nurulain Atikah; Zubairi, Saiful Irwan

    2016-01-01

    Clinacanthus nutans is widely grown in tropical Asia and locally known "belalai gajah" or Sabah snake grass. It has been used as a natural product to treat skin rashes, snake bites, lesion caused by herpes, diabetes, fever, and cancer. Therefore, the objectives of this research are to determine the maximum yield and time of exhaustive flavonoids extraction using Peleg's model and to evaluate potential of antiproliferative activity on human lung cancer cell (A549). The extraction process was carried out on fresh and dried leaves at 28 to 30°C with liquid-to-solid ratio of 10 mL/g for 72 hrs. The extracts were collected intermittently analysed using mathematical Peleg's model and RP-HPLC. The highest amount of flavonoids was used to evaluate the inhibitory concentration (IC50) via 2D cell culture of A549. Based on the results obtained, the predicted maximum extract density was observed at 29.20 ± 14.54 hrs of extraction (texhaustive). However, the exhaustive time of extraction to acquire maximum flavonoids content exhibited approximately 10 hrs earlier. Therefore, 18 hrs of extraction time was chosen to acquire high content of flavonoids. The best antiproliferative effect (IC50) on A549 cell line was observed at 138.82 ± 0.60 µg/mL. In conclusion, the flavonoids content in Clinacanthus nutans water extract possesses potential antiproliferative properties against A549, suggesting an alternative approach for cancer treatment.

  11. Antiproliferative activity of protein extracts from the black clam ...

    African Journals Online (AJOL)

    Hiessu

    2016-02-24

    Feb 24, 2016 ... from the screening of diverse marine invertebrates, such as soft corals, tunicates and ... Many peptides with different biological activities such as antioxidant ... were added in serial concentrations, PBS or Cisplatin as controls,.

  12. Hepatoprotective and antiproliferative activity of moringinine, chlorogenic acid and quercetin

    Directory of Open Access Journals (Sweden)

    Fahmy T. Ali

    2016-04-01

    Conclusions: Quercetin and moringinine are responsible to a great extent for the antitumor activity of the whole extract. Chlorogenic acid is a potent hepatoprotective in alloxan induced liver toxicity. [Int J Res Med Sci 2016; 4(4.000: 1147-1153

  13. Anti-proliferative activity of recombinant melittin expressed in ...

    African Journals Online (AJOL)

    kesiena

    2012-02-09

    Feb 9, 2012 ... activity, and then matured through deletion of N-terminal. 44 amino acid residues ... human renal, lung, liver, prostate, bladder and mammary cancer cells have been identified as targets of melittin. (Katoh, 1995; Son et al., ...

  14. In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae.

    Science.gov (United States)

    Formagio, A S N; Vieira, M C; Volobuff, C R F; Silva, M S; Matos, A I; Cardoso, C A L; Foglio, M A; Carvalho, J E

    2015-04-01

    The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE) inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI50) values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI50 values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%). Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

  15. In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae

    Directory of Open Access Journals (Sweden)

    A.S.N. Formagio

    2015-04-01

    Full Text Available The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI50 values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI50 values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%. Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

  16. In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae

    Energy Technology Data Exchange (ETDEWEB)

    Formagio, A.S.N.; Vieira, M.C. [Faculdade de Ciências Agrárias, Universidade Federal da Grande Dourados, Dourados, MS (Brazil); Volobuff, C.R.F.; Silva, M.S. [Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Dourados, MS (Brazil); Matos, A.I. [Faculdade de Ciências, Universidade de Lisboa, Lisboa (Portugal); Cardoso, C.A.L. [Curso de Química, Universidade Estadual do Mato Grosso do Sul, Dourados, MS (Brazil); Foglio, M.A.; Carvalho, J.E. [Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2015-02-13

    The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE) inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI{sub 50}) values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI{sub 50} values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%). Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

  17. [Peroxisome proliferator-activated receptors (PPAR). Antiproliferative properties].

    Science.gov (United States)

    Hojka, Anna; Rapak, Andrzej

    2011-06-21

    Peroxisome proliferator-activated receptors (PPAR) are transcription factors that belong to the hormone nuclear receptor superfamily. Their main role is control of fatty acid metabolism and to maintain glucose homeostasis. Isotype γ of PPAR can also be implicated in proliferation and cellular differentiation of both normal and cancer cells. Compounds that are PPARγ ligands have a negative influence on cancer cells and can induce apoptosis, inhibit proliferation or induce cellular differentiation of these cells. This review summarizes general information about PPAR and focuses on anticancer activities of PPARγ ligands and their use in combined therapy. Combination treatment using PPARγ ligands and other agents, especially retinoids and specific kinase inhibitors, may be an effective strategy for chemoprevention and treatment of some cancers.

  18. Antioxidant and antiproliferative activities of Helleborus odorus Waldst. & Kit, H. multifidus Vis. and H. hercegovinus Martinis.

    Science.gov (United States)

    Cakar, Jasmina; Parić, Adisa; Vidic, Danijela; Haverić, Anja; Haverić, Sanin; Maksimović, Milka; Bajrović, Kasim

    2011-12-01

    This study was undertaken in order to evaluate possible antioxidative and antiproliferative activities of three Helleborus taxa. The dry leaves and roots of three Helleborus taxa were extracted with ethanol and water. A phytochemical evaluation of the selected extracts was performed using spectrophotometric methods and a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity assay was used for measuring the antioxidative activity of extracts. The antiproliferative activity of the three Helleborus taxa was studied using Burkitt's lymphoma B cells (BJAB) cell lines. The phytochemical evaluation showed that the leaves contain high levels of total phenolic and flavonoid content. Results from the DPPH assay indicated that the activity of the ethanol and water extracts of the leaves was higher than that of positive control (thymol). Extracts from the roots of H. odorus also displayed higher antioxidant activity than the positive probe, while H. mulifidus and H. hercegovinus root extracts were less effective. A statistically significant correlation between total phenolic content and antioxidative properties indicates that these compounds contribute to the antioxidant activity. The highest percentage of cell growth inhibition was observed when testing the water root extracts of H. multifidus (50.14%) and H. hercegovinus (49.04%). In contrast, the water leaf extract of H. hercegovinus exhibited the lowest inhibition of cell growth (8.59%), although it showed strong antioxidant activity.

  19. Antiproliferative activity of Luehea candicans Mart. et Zucc. (Tiliaceae).

    Science.gov (United States)

    da Silva, Dioni A; Alves, Vanessa G; Franco, Danielle M M; Ribeiro, Laryssa C; de Souza, Maria C; Kato, Lucilia; de Carvalho, João E; Kohn, Luciana K; de Oliveira, Cecília M A; da Silva, Cleuza C

    2012-01-01

    Luehea candicans Mart. et Zucc. (Tiliaceae) is known as 'açoita-cavalo' and is one of the most important medicinal plants found in the Brazilian cerrado. The crude methanolic extracts of the branches and leaves and their fractions were evaluated using the following cancer cell lines: MCF-7 (breast), NCI-ADR (breast expressing the multidrug resistance phenotype), NCI-460 (lung), UACC-62 (melanoma), 786-0 (kidney), OVCAR (ovarian), PCO-3 (prostate), HT-29 (colon) and K-562 (leukaemia). The crude methanolic extracts from the branches (B) and leaves (L) were able to inhibit the growth of the K-562 and 786-0 cell lines in a dose-dependent manner, with GI(50) values of 8.1 and 5.4 µg mL(-1), respectively. The hexane (L1), chloroform (L2) and methanol (L4) fractions derived from extract L showed a high selectivity and pronounced cytostatic activity against 786-0 (GI(50) ~ 40 µg mL(-1)). A significant amount of lupeol was isolated from fraction L2. The chloroform (B2) and methanol (B3) fractions derived from extract (B) exhibited less selectivity, showing the highest cytostatic activity against K-562, NCI-ADR, OVCAR, MCF-7 and NCI-460 cells, with GI(50) values between 27 and 40 µg mL(-1). Lupeol, betulin, a mixture of steroids, (-)-epicatechin, vitexin and liriodendrin were isolated from these active fractions.

  20. Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities.

    Science.gov (United States)

    Guan, Qi; Han, Chunming; Zuo, Daiying; Zhai, Min'an; Li, Zengqiang; Zhang, Qian; Zhai, Yanpeng; Jiang, Xuewei; Bao, Kai; Wu, Yingliang; Zhang, Weige

    2014-11-24

    A series of novel benzimidazole carbamates bearing indole moieties with sulphur or selenium atoms connecting the aromatic rings were synthesised and evaluated for their antiproliferative activities against three human cancer cell lines (SGC-7901, A-549 and HT-1080) using an MTT assay. Compounds 10a, 10b, 7a, 7b and 7f showed significant activities against these cell lines. The most potent compound in this series, 10a, was selected to investigate its antitumour mechanism. In addition, molecular docking studies suggested that compound 10a interacts very closely with the nocodazole docking pose through hydrogen bonds at the colchicine binding site of tubulin.

  1. In vitro and in vivo antiproliferative and trypanocidal activities of ruthenium NO donors

    Science.gov (United States)

    Silva, J J N; Osakabe, A L; Pavanelli, W R; Silva, J S; Franco, D W

    2007-01-01

    Background and purpose: Many compounds liberating NO (NO donors) have been used as therapeutic agents. Here we test two ruthenium nitrosyls, which release NO when activated by biological reducing agents, for their effects in vitro and in vivo against Trypanasoma cruzi, the agent responsible for the American trypanosomiasis (Chagas' disease). Experimental approach: Ruthenium NO donors were incubated with a partially drug-resistant strain of T. cruzi and the anti-proliferative and trypanocidal activities evaluated. In a mouse model of acute Chagas' disease, trypanocidal activity was evaluated by measuring parasitemia, survival rate of infected mice and elimination of amastigotes in myocardial tissue. Key results: In vitro, the observed anti-proliferative and trypanocidal activities of trans-[Ru(NO)(NH3)4isn](BF4)3 and trans-[Ru(NO)(NH3)4imN](BF4)3 were due to NO liberated upon reduction of these nitrosyls. Ru(NO)isn had a lower IC50epi (67 μM) than the NO donor, sodium nitroprusside (IC50epi=244 μM) and Ru(NO)imN (IC50try=52 μM) was more potent than gentian violet (IC50try=536 μM), currently used in the treatment of blood. Both ruthenium nitrosyls eliminated, in vivo, extracellular as well as intracellular forms of T. cruzi in the bloodstream and myocardial tissue and allowed survival of up to 80% of infected mice at a dose (100 nmol kg−1 day−1) much lower than the optimal dose for benznidazole (385 μmol kg−1 day−1). Conclusions and implications: Our data strongly suggest that NO liberated is responsible for the anti-proliferative and trypanocidal activities of the ruthenium NO donors and that these compounds are promising leads for novel and effective anti-parasitic drugs. PMID:17603548

  2. Varietal differences in phenolic content and antioxidant and antiproliferative activities of onions.

    Science.gov (United States)

    Yang, Jun; Meyers, Katherine J; van der Heide, Jan; Liu, Rui Hai

    2004-11-03

    Epidemiological studies have indicated that the consumption of fruits and vegetables is associated with a reduced risk for the development of chronic diseases, such as cardiovascular disease and cancer. Phytochemicals, including phenolics and flavonoids, are suggested to be the major bioactive compounds contributing to the health benefits of fruits and vegetables. Onions are a major source of dietary flavonoids; however, there may exist varietal differences in composition, concentration, and beneficial activities. To characterize these differences, shallots and 10 onion (Allium cepa L.) varieties commonly available in the United States (Western Yellow, Northern Red, New York Bold, Western White, Peruvian Sweet, Empire Sweet, Mexico, Texas 1015, Imperial Valley Sweet, and Vidalia) were evaluated for total phenolic and flavonoid contents and antioxidant and antiproliferative activities. Shallots contained the highest total phenolic content (114.7 +/- 10.0 mg/100 g of sample) among the varieties tested, with a 6-fold difference observed when compared to the variety with the lowest phenolic content (Vidalia, p Western Yellow onion variety exhibited the highest total flavonoid content (69.2 +/- 3.7 mg/100 g of onion) of the varieties tested, with an 11-fold difference when compared to the variety with the lowest flavonoid content (Western White, p Western Yellow, New York Bold, Northern Red, Mexico, Empire Sweet, Western White, Peruvian Sweet, Texas 1015, Imperial Valley Sweet, and Vidalia. For all varieties, both total phenolic and flavonoid contents were strongly correlated with total antioxidant activity (R (2) = 0.9668, p fashion after exposure to the Western Yellow, shallots, New York Bold, and Northern Red extracts, with Western Yellow, shallots, and New York Bold exhibiting the highest antiproliferative activity against HepG(2) cells and New York Bold and Western Yellow exhibiting the highest antiproliferative activity against Caco-2 cells. However, the varieties

  3. Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues.

    Science.gov (United States)

    Wang, Yue-Hu; Goto, Masuo; Wang, Li-Ting; Hsieh, Kan-Yen; Morris-Natschke, Susan L; Tang, Gui-Hua; Long, Chun-Lin; Lee, Kuo-Hsiung

    2014-10-15

    Twenty-five amide alkaloids (1-25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39-48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl)heptanoyl]piperidine (46) exhibited the best inhibitory activity (IC50=4.94 μM) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC50 >40 μM) against MDA-MB-231 and SK-BR-3. Structure-activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype.

  4. In vitro antioxidant and antiproliferative activities of flavonoids from Ailanthus excelsa (Roxb.) (Simaroubaceae) leaves.

    Science.gov (United States)

    Said, Ataa; Tundis, Rosa; Hawas, Usama W; El-Kousy, Salah M; Rashed, Khaled; Menichini, Federica; Bonesi, Marco; Huefner, Antje; Loizzo, Monica Rosa; Menichinib, Francesco

    2010-01-01

    The present study aimed to investigate the chemical composition, and the antioxidant and antiproliferative activities of Ailanthus excelsa, a plant used in Egyptian traditional medicine. Chromatographic separation of a methanol extract of A. excelsa leaves yielded four flavones, namely apigenin (1), apigenin 7-O-beta-glucoside (2), luteolin (3), and luteolin 7-O-beta-glucoside (4), and seven flavonols, namely kaempferol (5), kaempferol 3-O-alpha-arabinoside (6), kaempferol 3-O-beta-galactoside (7), quercetin (8), quercetin 3-O-alpha-arabinoside (9), quercetin 3-O-beta-galactoside (10), and quercetin 3-O-rutinoside (11). The A. excelsa extract tested in different in vitro systems (DPPH and FRAP assays) showed significant antioxidant activity. The potential antiproliferative activity of the A. excelsa extract and isolated flavonoids against five human cancer cell lines such as ACHN, COR-L23, A375, C32, and A549 was investigated in vitro by the SRB assay in comparison with one normal cell line, 142BR. The extract exhibited the highest inhibitory activity against C32 cells with an IC50 value of 36.5 microg ml(-1). Interesting activity against COR-L23 was found with 10 (IC50 value of 3.2 microg ml(-1)). Compounds 1 and 3 inhibited cell growth in both amelanotic melanoma and malignant melanoma cells.

  5. Synthesis, characterization and antiproliferative activity of β-aryl-δ-iodo-γ-lactones

    Science.gov (United States)

    Wzorek, Alicja; Gawdzik, Barbara; Gładkowski, Witold; Urbaniak, Mariusz; Barańska, Anita; Malińska, Maura; Woźniak, Krzysztof; Kempińska, Katarzyna; Wietrzyk, Joanna

    2013-09-01

    A convenient pathway for the synthesis of new of β-aryl-δ-iodo-γ-lactones is described. The synthetic route led to both cis and trans isomers which were separated by column chromatography or crystallization. The structures of synthesized compounds were confirmed by spectroscopic methods: IR, NMR and HR-MS. For lactones with naphthyl ring (6e and 7e) the crystal structures were also obtained. The lactones were screened for biological evaluation against cancer line HL-60 (human promyelocytic leukemia). The tests showed that the presence of substituent at the benzene ring does not significantly affect the antiproliferative activity of the compound.

  6. Synthesis and In Vitro Antiproliferative Activity of Novel Androst-5-ene Triazolyl and Tetrazolyl Derivatives

    Directory of Open Access Journals (Sweden)

    János Wölfling

    2011-06-01

    Full Text Available A straightforward and reliable method for the regioselective synthesis of steroidal 1,4-disubstituted triazoles and 1,5-disubstituted tetrazoles via copper(I-catalyzed cycloadditions is reported. Heterocycle moieties were efficiently introduced onto the starting azide compound 3β-acetoxy-16β-azidomethylandrost-5-en-17β-ol through use of the “click” chemistry approach. The antiproliferative activities of the newly-synthesized triazoles were determined in vitro on three human gynecological cell lines (HeLa, MCF7 and A2780 using the microculture tetrazolium assay.

  7. Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

    Science.gov (United States)

    Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

    2010-01-01

    The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

  8. Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives.

    Science.gov (United States)

    Gaballah, Samir T; El-Nezhawy, Ahmed O H; Amer, Hassan; Ali, Mamdouh Moawad; Mahmoud, Abeer Essam El-Din; Hofinger-Horvath, Andreas

    2016-01-01

    The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

  9. Cytotoxicity and Antiproliferative Activity Assay of Clove Mistletoe (Dendrophthoe pentandra (L. Miq. Leaves Extracts

    Directory of Open Access Journals (Sweden)

    Vida Elsyana

    2016-01-01

    Full Text Available Clove mistletoe (Dendrophthoe pentandra (L. Miq. is a semiparasitic plant that belongs to Loranthaceae family. Clove mistletoe was traditionally used for cancer treatment in Indonesia. In the present study, we examined cytotoxicity of clove mistletoe leaves extracts against brine shrimps and conducted their antiproliferative activity on K562 (human chronic myelogenous leukemia and MCM-B2 (canine benign mixed mammary cancer cell lines in vitro. The tested samples were water extract, ethanol extract, ethanol fraction, ethyl acetate fraction, and n-hexane fraction. Cytotoxicity was screened using Brine Shrimp Lethality Test (BSLT. Antiproliferative activity was conducted using Trypan Blue Dye Method and cells were counted using haemocytometer. The results showed that n-hexane fraction exhibited significant cytotoxicity with LC50 value of 55.31 μg/mL. The n-hexane fraction was then considered for further examination. The n-hexane fraction of clove mistletoe could inhibit growth of K562 and MCM-B2 cancer cell lines in vitro. The inhibition activity of clove mistletoe n-hexane fraction at concentration of 125 μg/mL on K562 cancer cell lines was 38.69%, while on MCM-B2 it was 41.5%. Therefore, it was suggested that clove mistletoe had potential natural anticancer activity.

  10. Chitin and chitosan from the Norway lobster by-products: Antimicrobial and anti-proliferative activities.

    Science.gov (United States)

    Sayari, Nadhem; Sila, Assaâd; Abdelmalek, Baha Eddine; Abdallah, Rihab Ben; Ellouz-Chaabouni, Semia; Bougatef, Ali; Balti, Rafik

    2016-06-01

    Chitin was recovered through enzymatic deproteinization of the Norway lobster (Nephrops norvegicus) processing by-products. The obtained chitin was characterized and converted into chitosan by N-deacetylation, the acid-soluble form of chitin. Chitosan samples were then characterized by Fourier transform infrared spectroscopy (FTIR) and 13 Cross polarization magic angle spinning nuclear magnetic resonance (CP/MAS)-NMR spectroscopy. The antimicrobial activity and anti-proliferative capacity of chitosan were evaluated. Antimicrobial activity assays indicated that prepared chitosan exhibited marked inhibitory activity against the bacterial and fungal strains tested. Further, cytotoxic effects of chitosan samples on human colon carcinoma cells HCT116 was evaluated using the MTT assay. Chitosan showed the antiproliferative capacity against the colon-cancer-cell HCT116 in a dose dependent manner with IC50 of 4.6mg/ml. Indeed, HCT116 cell proliferation was significantly inhibited (p<0.05) between 13.5 and 67.5% at 0.5-6mg/mL of chitosan after 24h of cell treatment. The chitosan showed high antitumor activity which seemed to be dependent on its characteristics such as acetylation degree.

  11. Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin

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    Adriana Basile

    2015-04-01

    Full Text Available Lichens are valuable natural resources used for centuries throughout the world as medicine, food, fodder, perfume, spices and dyes, as well as for other miscellaneous purposes. This study investigates the antiproliferative, antibacterial and antifungal activity of the acetone extract of the lichen Xanthoria parietina (Linnaeus Theodor Fries and its major secondary metabolite, parietin. The extract and parietin were tested for antimicrobial activity against nine American Type Culture Collection standard and clinically isolated bacterial strains, and three fungal strains. Both showed strong antibacterial activity against all bacterial strains and matched clinical isolates, particularly against Staphylococcus aureus from standard and clinical sources. Among the fungi tested, Rhizoctonia solani was the most sensitive. The antiproliferative effects of the extract and parietin were also investigated in human breast cancer cells. The extract inhibited proliferation and induced apoptosis, both effects being accompanied by modulation of expression of cell cycle regulating genes such as p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL and B-cell lymphoma 2 (Bcl-2, and inducing Bcl-2-associated agonist of cell death (BAD phosphorylation. Our results indicate that Xanthoria parietina is a major potential source of antimicrobial and anticancer substances.

  12. Antiproliferative, Cytotoxic, Antioxidant Activity and Polyphenols Contents in Leaves of Four Staphylea L. Species

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    Daniel Grancai

    2009-08-01

    Full Text Available Staphylea has been used for long time in Traditional Chinese Medicine (TCM and by Native Americans in a number of therapeutical indications. The present study describes in vitro antiproliferative, cytotoxic properties (MTT and LDH test and antioxidant activities (reduction of DPPH radical and peroxynitrite radical of Staphylea colchica Stev. (SC, S. elegans Zab. (SC, S. holocarpa Hemsl. (SH and S. pinnata L. (SP leave water extracts. Time- (24 and 72 h and dose- (1-150 μg/mL dependent effects of the above extracts were tested at the mitochondrial (MTT test and plasma membrane level (LDH leakage in A431 human skin carcinoma cells. Screening of these properties has shown time and dose dependent increase of harmful effects, the highest activity was observed for the SE, while the less active was the SH extract. The ED50 values for the mitochondrial and membrane damage were nearly identical for the SE and very similar for SH extract. These findings indicate simultaneous injury of both cell compartments by SE and SH extracts. The highest antioxidant potential of SE species is accompanied by the highest content of flavones/flavonols and polyphenols. Only flavonoid contents are associated with antiproliferative effects and cell membrane injury, while antioxidant properties are the result of polyphenol content. The data clearly demonstrate that individual Staphylea L. species differ, not only in the amount of biologically active compounds, but also by the extent of harmful and beneficial effects.

  13. High Performance Liquid Chromatography-mass Spectrometry Analysis of High Antioxidant Australian Fruits with Antiproliferative Activity Against Cancer Cells

    Science.gov (United States)

    Sirdaarta, Joseph; Maen, Anton; Rayan, Paran; Matthews, Ben; Cock, Ian Edwin

    2016-01-01

    Background: High antioxidant capacities have been linked to the treatment and prevention of several cancers. Recent reports have identified several native Australian fruits with high antioxidant capacities. Despite this, several of these species are yet to be tested for anticancer activity. Materials and Methods: Solvent extracts prepared from high antioxidant native Australian fruits were analyzed for antioxidant capacity by the di (phenyl)-(2,4,6-trinitrophenyl) iminoazanium free radical scavenging assay. Antiproliferative activities against CaCo2 and HeLa cancer cells were determined by a multicellular tumor spheroid-based cell proliferation assay. Toxicity was determined by Artemia franciscana bioassay. Results: Methanolic extracts of all plant species displayed high antioxidant contents (equivalent to approximately 7–16 mg of vitamin C per gram of fruit extracted). Most aqueous extracts also contained relatively high antioxidant capacities. In contrast, the ethyl acetate, chloroform, and hexane extracts of most species (except lemon aspen and bush tomato) had lower antioxidant contents (below 1.5 mg of vitamin C equivalents per gram of plant material extracted). The antioxidant contents correlated with the ability of the extracts to inhibit proliferation of CaCo2 and HeLa cancer cell lines. The high antioxidant methanolic extracts of all species were potent inhibitors of cell proliferation. The methanolic lemon aspen extract was particularly effective, with IC50 values of 480 and 769 μg/mL against HeLa and CaCo2 cells, respectively. In contrast, the lower antioxidant ethyl acetate and hexane extracts (except the lemon aspen ethyl acetate extract) generally did not inhibit cancer cell proliferation or inhibited to only a minor degree. Indeed, most of the ethyl acetate and hexane extracts induced potent cell proliferation. The native tamarind ethyl acetate extract displayed low-moderate toxicity in the A. franciscana bioassay (LC50 values below 1000

  14. Phytochemical screening, antiproliferative and cytotoxic activities of the mosses Rhytidiadelphus triquetrus (Hedw. Warnst. and Tortella tortuosa (Hedw. Limpr.

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    Muhammet Şamil Yağlıoğlu

    2017-06-01

    Full Text Available The paper presents information about the phytochemical analysis, antiproliferative and cytotoxic activities of Rhytidiadelphus triquetrus and Tortella tortuosa extracts. The cytotoxic activities of some extracts shows highest antiproliferative activities were detected with Lactate Dehydrogenase Leakage Assay. Sixteen components obtained from hexane extracts were determined by GC/MS. Palmitic acid was identified as the main component. The phenolic components of the other extracts were determined by HPLC-TOF/MS. 4-hydroxy benzoic acid, salicylic acid, gallic acid, caffeic acid, and gensitic acid were detected as the main components in all extracts. The hexane, chloroform, ethyl acetate extracts of studied mosses and the EtOAc and hexane extracts of R. triquetrus showed statistically significant antiproliferative activities.

  15. Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones

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    Juana Andrea Ibacache

    2014-01-01

    Full Text Available The synthesis of a variety of 1-aryl-7-phenylaminoisoquinolinequinones from 1,4-benzoquinone and arylaldehydes via the respective 1-arylisoquinolinequinones is reported. The cyclic voltammograms of the new compounds exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasi-reversible oxidation peaks. The half-wave potential values (EI½ of the members of the series have proven sensitive to the electron-donor effect of the aryl group (phenyl, 2-thienyl, 2-furyl at the 1-position as well as to the phenylamino groups (anilino, p-anisidino at the 7-position. The antiproliferative activity of the new compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (MRC-5 lung fibroblasts and two human cancer cell lines: AGS human gastric adenocarcinoma and HL-60 human promyelocytic leukemia cells in 72-h drug exposure assays. Among the series, compounds 5a, 5b, 5g, 5h, 6a and 6d exhibited interesting antiproliferative activities against human gastric adenocarcinoma. The 1-arylisoquinolinequinone 6a was found to be the most promising active compound against the tested cancer cell lines in terms of IC50 values (1.19; 1.24 µM and selectivity index (IS: 3.08; 2.96, respect to the anti-cancer agent etoposide used as reference (IS: 0.57; 0.14.

  16. Fungal metabolites of xanthohumol with potent antiproliferative activity on human cancer cell lines in vitro.

    Science.gov (United States)

    Tronina, Tomasz; Bartmańska, Agnieszka; Filip-Psurska, Beata; Wietrzyk, Joanna; Popłoński, Jarosław; Huszcza, Ewa

    2013-04-01

    Xanthohumol (1) and xanthohumol D (2) were isolated from spent hops. Isoxanthohumol (3) was obtained from xanthohumol by isomerisation in alkaline solution. Six metabolites were obtained as a result of transformation of xanthohumol (1) by selected fungal cultures. Their structures were established on the basis of their spectral data. One of them: 2″-(2'''-hydroxyisopropyl)-dihydrofurano-[4″,5″:3',4']-4',2-dihydroxy-6'-methoxy-α,β-dihydrochalcone (6) has not been previously reported in the literature. The antioxidant properties of hops flavonoids and xanthohumol derivatives were investigated using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The effects of these compounds on proliferation of MCF-7, PC-3 and HT-29 human cancer cell lines were determined by the SRB assay. With the exception of one metabolite, all tested compounds showed antiproliferative activity against the tested human cancer lines. α,β-Dihydroxanthohumol (4), obtained through the biotransformation of xanthohumol, showed higher antiproliferative activity against MCF-7 human breast carcinoma cell line than cisplatin, a widely used anticancer therapeutic agent, and a comparably high activity against PC-3 human prostate cancer cell line.

  17. Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis By-Products

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    Marie-Elise Carbonneau

    2013-03-01

    Full Text Available Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.

  18. [Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

    Science.gov (United States)

    Gao, Liu-zhou; Xie, Yu-suo; Yan, Qiang; Wu, Shu-min; Ni, Li-li; Zhao, Hui; Huang, Wen-long; Hu, Guo-qiang

    2015-08-01

    To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

  19. Antiproliferative activity of bicyclic benzimidazole nucleosides: synthesis, DNA-binding and cell cycle analysis.

    Science.gov (United States)

    Sontakke, Vyankat A; Lawande, Pravin P; Kate, Anup N; Khan, Ayesha; Joshi, Rakesh; Kumbhar, Anupa A; Shinde, Vaishali S

    2016-04-26

    An efficient route was developed for synthesis of bicyclic benzimidazole nucleosides from readily available d-glucose. The key reactions were Vörbruggen glycosylation and ring closing metathesis (RCM). Primarily, to understand the mode of DNA binding, we performed a molecular docking study and the binding was found to be in the minor groove region. Based on the proposed binding model, UV-visible and fluorescence spectroscopic techniques using calf thymus DNA (CT-DNA) demonstrated a non-intercalative mode of binding. Antiproliferative activity of nucleosides was tested against MCF-7 and MDA-MB-231 breast cancer cell lines and found to be active at low micromolar concentrations. Compounds and displayed significant antiproliferative activity as compared to and with the reference anticancer drug, doxorubicin. Cell cycle analysis showed that nucleoside induced cell cycle arrest at the S-phase. Confocal microscopy has been performed to validate the induction of cellular apoptosis. Based on these findings, such modified bicyclic benzimidazole nucleosides will make a significant contribution to the development of anticancer drugs.

  20. Antiproliferative activity of the hexanic extract and phloroglucinols from Hypericum brasiliense

    Directory of Open Access Journals (Sweden)

    Hildegardo Seibert França

    2013-10-01

    Full Text Available Natural products are regarded as major and important sources of molecules used in chemotherapy. Hypericum brasiliense Choisy, Hypericaceae, is an annual bush, native in the southern and southeastern Brazil. This species has been used in Brazilian folk medicine the anti-spasmodic and for the treatment of infectious diseases. H. brasiliense is chemically composed by flavonoids and xanthones. In addition, this species contain phloroglucinols, a class of substances with citotoxity effects against tumor cells lines. On the present study, hexanic extract and derivatives phloroglucinols obtained from H. brasiliense were tested against some human tumor cell lines. Hexanic extract presented a potent antiproliferative activity, with selective action on OVCAR-03 (ovarian, NCIADR/ RES (ovarian resistant and UACC-62 (melanoma tumor cell lines. Uliginosin B was the most active derivative phloroglucinol, presenting selectivity against NCI-ADR/ RES ( resistant ovarian and OVCAR-03 (ovarian tumor cell lines. Analysis of the results suggests that phloroglucinol derivatives with isoprenyl unit closed in the 9' position increases antiproliferative activity. Furthermore, this study contributes to identification of anti-tumor molecules and valorization of Hypericum brasiliense.

  1. Chemical compositions, antioxidant capacities, and antiproliferative activities of selected fruit seed flours.

    Science.gov (United States)

    Parry, John; Su, Lan; Moore, Jeffrey; Cheng, Zhihong; Luther, Marla; Rao, Jaladanki N; Wang, Jian-Ying; Yu, Liangli Lucy

    2006-05-31

    Seed flours from black raspberry, red raspberry, blueberry, cranberry, pinot noir grape, and chardonnay grape were examined for their total fat content, fatty acid composition, total phenolic content (TPC), total anthocyanin content (TAC), radical scavenging capacities against the peroxyl (ORAC) and stable DPPH radicals, chelating capacity against Fe(2+), and antiproliferative activities using the HT-29 colon cancer cell line. Significant levels of fat were detected in the fruit seed flours and their fatty acid profiles may differ from those of the respective seed oils. Cranberry seed flour had the highest level of alpha-linolenic acid (30.9 g/100 g fat) and the lowest ratio of n-6/n-3 fatty acids (1.2/1). The ORAC value of the chardonnay seed flour was 1076.4 Trolox equivalents mumol/g flour, and its TPC was 186.3 mg gallic acid equivalents/g flour. These values were 3-12 times higher than the other tested fruit seed flours. Furthermore, the ORAC value was significantly correlated to the TPC under the experimental conditions (P seed flours also differed in their TAC values and Fe(2+)-chelating capacities. In addition, black raspberry, cranberry, and chardonnay grape seed flour extracts were evaluated for their antiproliferative effects using HT-29 colon cancer cells. All three tested seed flour extracts significant inhibited HT-29 cell proliferation. The data from this study suggest the potential of developing the value-added use of these fruit seed flours as dietary sources of natural antioxidants and antiproliferative agents for optimal human health.

  2. Kinetics Extraction Modelling and Antiproliferative Activity of Clinacanthus nutans Water Extract

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    Farah Nadiah Mohd Fazil

    2016-01-01

    Full Text Available Clinacanthus nutans is widely grown in tropical Asia and locally known “belalai gajah” or Sabah snake grass. It has been used as a natural product to treat skin rashes, snake bites, lesion caused by herpes, diabetes, fever, and cancer. Therefore, the objectives of this research are to determine the maximum yield and time of exhaustive flavonoids extraction using Peleg’s model and to evaluate potential of antiproliferative activity on human lung cancer cell (A549. The extraction process was carried out on fresh and dried leaves at 28 to 30°C with liquid-to-solid ratio of 10 mL/g for 72 hrs. The extracts were collected intermittently analysed using mathematical Peleg’s model and RP-HPLC. The highest amount of flavonoids was used to evaluate the inhibitory concentration (IC50 via 2D cell culture of A549. Based on the results obtained, the predicted maximum extract density was observed at 29.20 ± 14.54 hrs of extraction (texhaustive. However, the exhaustive time of extraction to acquire maximum flavonoids content exhibited approximately 10 hrs earlier. Therefore, 18 hrs of extraction time was chosen to acquire high content of flavonoids. The best antiproliferative effect (IC50 on A549 cell line was observed at 138.82 ± 0.60 µg/mL. In conclusion, the flavonoids content in Clinacanthus nutans water extract possesses potential antiproliferative properties against A549, suggesting an alternative approach for cancer treatment.

  3. Antiproliferative activity of Curcuma phaeocaulis Valeton extract using ultrasonic assistance and response surface methodology.

    Science.gov (United States)

    Wang, Xiaoqin; Jiang, Ying; Hu, Daode

    2017-01-02

    The objective of the study was to optimize the ultrasonic-assisted extraction of curdione, furanodienone, curcumol, and germacrone from Curcuma phaeocaulis Valeton (Val.) and investigate the antiproliferative activity of the extract. Under the suitable high-performance liquid chromatography condition, the calibration curves for these four tested compounds showed high levels of linearity and the recoveries of these four compounds were between 97.9 and 104.3%. Response surface methodology (RSM) combining central composite design and desirability function (DF) was used to define optimal extraction parameters. The results of RSM and DF revealed that the optimum conditions were obtained as 8 mL g(-1) for liquid-solid ratio, 70% ethanol concentration, and 20 min of ultrasonic time. It was found that the surface structures of the sonicated herbal materials were fluffy and irregular. The C. phaeocaulis Val. extract significantly inhibited the proliferation of RKO and HT-29 cells in vitro. The results reveal that the RSM can be effectively used for optimizing the ultrasonic-assisted extraction of bioactive components from C. phaeocaulis Val. for antiproliferative activity.

  4. Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Jie, Meng; Cheung, Wan Man; Yu, Vivian; Zhou, Yanling; Tong, Pak Ho; Ho, John W S

    2014-01-01

    Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.

  5. Antiproliferative and hepatoprotective activity of metabolites from Corynebacterium xerosis against Ehrlich Ascites Carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Farhadul Islam; Soby Ghosh; Jahan Ara Khanam

    2014-01-01

    Objective: To find out the effective anticancer drugs from bacterial products, petroleum ether extract of Corynebacterium xerosis.Methods:parameters like tumor weight measurement, tumor cell growth inhibition in mice and survival time of tumor bearing mice, etc. Hepatoprotective effect of the metabolites was determined by observing biochemical, hematological parameters.Results:It has been found that the petroleum ether extract bacterial metabolite significantly Antiproliferative activity of the metabolite has been measured by monitoring the decrease cell growth (78.58%; P<0.01), tumor weight (36.04 %; P<0.01) and increase the life span of tumor bearing mice (69.23%; P<0.01) at dose 100 mg/kg (i.p.) in comparison to those of untreated Ehrlich ascites carcinoma (EAC) bearing mice. The metabolite also alters the depleted hematological parameters like red blood cell, white blood cell, hemoglobin (Hb%), etc. towards normal in tumor bearing mice. Metabolite show no adverse effect on liver functions regarding blood glucose, serum alkaline phosphatases, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase activity and serum billirubin, etc. in normal mice. Histopathological observation of these mice organ does not show any toxic effect on cellular structure. But in the case of EAC bearing untreated mice these hematological and biochemical parameters deteriorate extremely with time whereas petroleum ether extract bacterial metabolite receiving EAC bearing mice nullified the toxicity induced by EAC cells.Conclusion:Study results reveal that metabolite possesses significant antiproliferative and hepatoprotective effect against EAC cells.

  6. Antiproliferative Activities of Chemical Constituents Isolated from Thymus praecox subsp. grossheimii (Ronniger Jalas

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    Ramazan Erenler

    2016-05-01

    Full Text Available Thymus praecox subsp. grossheimii (Ronniger Jalas is (TPGJ an aromatic and medicinal plant used as folk medicine and exhibits a variety of biological activities. Aerial part of plant material was boiled in water then extracted with hexane and ethyl acetate sequentially. Flash column chromatography (Sephadex LH-20 and HPLC were used for ethy acetate extract to isolate rosmarinic acid (1, apigenin 7-O-glucoside (2, chrysoeriol (3, apigenin (4, naringenin (5 , eriodictiol (6, luteolin (7 and globoidnan A (8. The structures of isolated compounds were elucidated by spectroscopic techniques basically 1D, 2D-NMR and LC-TOF/MS/MS. Antiproliferative activity, cytotoxicity of compounds and extract were investigated in vitro on C6 (rat brain tumor, HeLa (human cervix carcinoma, HT29 (human colon carcinoma and Vero (African green monkey kidney epithelium cells lines by using BrdU cell proliferation ELISA and lactate dehydrogenase (LDH assays. Extract and some compounds exhibited significant antiproliferative effects against various cancerous cell lines.

  7. Anti-proliferative activity of Fumaria vaillantii extracts on different cancer cell lines

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    Fatemeh Haji Abbas Tabrizi

    2016-01-01

    Full Text Available Plant-derived natural products are known to have cancer chemo-preventive and chemo-therapeutic properties. Plant extracts or their active constituents are used as folk medicine in traditional therapies by 80% of the world population. The aim of the present study was to determine the anti-proliferative potential of Fumaria vaillantii extracts on three different cancer cell lines including malignant melanoma SKMEL-3, human breast adenocarcinoma MCF-7 and human myelogenous leukemia K562 as well as human gingival fibroblast (HGF as normal cell line. Anti-proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, flowcytometry and annexin methods. Total phenolics and flavonoids were determined by Folin-Ciocalteu and aluminum chloride methods. Chloroform fraction had the lowest IC 50 value at 72 h (0.1 μg/ml in MCF-7 cells. Flowcytometry and annexin-V analysis indicated that the chloroform fraction induced necrosis in MCF-7 cells. In addition, the colorimetric methods showed that the methanolic fraction possessed the highest amount of total phenolics (33.03 ± 0.75 mg/g of dry powder and flavonoids (10.5 ± 2.0 mg/g of dry powder.The collective data demonstrated that F. vaillantii chloroform fraction may contain effective compounds with chemo-therapeutic potential act through an apoptotic independent pathway.

  8. Chemical constituents isolated from the bark of Guatteria blepharophylla (Annonaceae) and their antiproliferative and antimicrobial activities

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Emmanoel V.; Marques, Francisco de Assis; Maia, Beatriz H.L.N.S., E-mail: noronha@ufpr.b [Universidade Federal do Parana (DQ/UFPR), Curitiba, PR (Brazil). Dept. de Quimica; Pinheiro, Maria Lucia B. [Universidade Federal do Amazonas (DQ/UFAM), Manaus, AM (Brazil). Dept. de Quimica; Braga, Raquel M. [Universidade Estadual de Campinas (IQ/UNICAMP), SP (Brazil). Inst. de Quimica; Delarmelina, Camila; Duarte, Marta Cristina T.; Ruiz, Ana Lucia T.G.; Carvalho, Joao Ernesto de [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Div. de Microbiologia e Div. Farmacologia e Toxicologia

    2011-07-01

    Phytochemical study of the bark of Guatteria blepharophylla (Mart.) Mart. afforded twelve compounds, namely two sesquiterpenes, caryophyllene oxide (1) and spathulenol (3), one xanthone, lichexanthone (2), a mixture of steroids, b-sitosterol (4), and stigmasterol (5), and seven isoquinoline alkaloids, O-methylmoschatoline (6), lysicamine (7), nornuciferine (8), liriodenine (9), isocoreximine (10), subsessiline (11), and isomoschatoline (12). Their structures were established on the basis of spectroscopic methods. Compounds 1-6, 11 and 12 were reported for the first time in this species. The {sup 13}C NMR (nuclear magnetic resonance) data for the compounds 11 and 12 are described for the first time in the literature. The antiproliferative activity against human tumour cell lines and antimicrobial activities were investigated for the major compounds. Compound 9 showed significant activity against cell lines of breast (MCF-7, Michigan Cancer Foundation-7), superior to the positive control doxorubicin. Compound 12 presented antifungal activity similar to the positive control nystatin against Candida albicans. (author)

  9. ANTIPROLIFERATIVE ACTIVITY OF HUMAN IFN-γ-EGF3 FUSION PROTEIN ARE RELATED TO ITS EGF RECEPTOR COMPETITION

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The relationship between antiproliferative effect of human IFN-γ-EGF3 fusion protein and the influence of EGF receptor binding activity has been studied on A431 cell line. Antiproliferative activity of human IFN-γ-EGF3 was higher than that of its parent IFN-γ. In the 125 I-EGF receptor competition experiment, the inhibition of EGF receptor binding capacity on the target cells was observed in the treatments of human IFN-γ or IFN-γ-EGF3, but the later was more significant. Our data suggests that the antiproliferative effects by IFN-γ and its fusion protein are closely related to their EGF receptor competitions.

  10. Optimization of polysaccharides extraction from Tricholoma mongolicum Imai and their antioxidant and antiproliferative activities.

    Science.gov (United States)

    Wang, Jin; Zhao, Yongming; Li, Wei; Wang, Zhibao; Shen, Lixia

    2015-10-20

    Response surface methodology was used to optimize the enzyme-assisted extraction parameters for polysaccharides from Tricholoma mongolicum Imai (TMIPs). The orthogonal test design was employed to determine the optimal concentration of three kinds of enzyme (trypsin, pectinase and papain) and the optimal concentrations of trypsin, pectinase and papain were 1.5%, 2.5%, and 2.0% (dry weight % of T. mongolicum Imai powder), respectively. In addition, three variables that remarkably affected the yield of polysaccharides such as extraction temperature, pH and extraction time were studied based on a Box-Behnken design. The results demonstrated that extraction time was the most remarkable factor affecting the TMIPs yield, followed by pH and temperature. Optimal extraction was obtained at 48.4°C, pH 5.4, and extraction time of 132min. Under these optimum conditions, the yield was 24.01%, which is consistent with the predicted value. Furthermore, crude polysaccharides were purified to obtain four fractions. In vitro antioxidant and antiproliferative activities results showed that TMIP-4 had stronger antioxidant and antiproliferative capacity than other fractions.

  11. Ginsenoside composition and antiproliferative activities of explosively puffed ginseng (Panax ginseng C.A. Meyer).

    Science.gov (United States)

    Yoon, Sung-Ran; Lee, Gee-Dong; Park, Jung-Hyun; Lee, In-Seon; Kwon, Joong-Ho

    2010-05-01

    The puffing process was evaluated as an alternative to the steaming process for producing a biologically more active ginseng product, like red ginseng, from raw ginseng. A puffing treatment of dried raw ginseng roots induced an overall increase in crude saponin content. As puffing pressure increased, the content of ginsenoside Re, Rg1, Rb1, Rc, and Rb2 decreased, while ginsenoside Rg3 increased significantly as compared to raw ginseng. The content of ginsenoside Rg3 in puffed ginseng at a pressure of 490 kPa was similar to that of red ginseng. Cancer cell lines (HeLa, MCF-7, and HepG2) showed that antiproliferative effects of saponin extract of puffed ginseng increased with an increase in puffing pressure. Ginseng explosively puffed at 490 kPa had similar saponin constituents and antiproliferative effects as those of red ginseng. The puffing process could provide an alternative mean to produce functional ginseng products, along with a reduction in processing time as compared to traditional red ginseng processing by steam.

  12. Antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of Psidium guineense Sw. and spathulenol.

    Science.gov (United States)

    do Nascimento, Kamilla Felipe; Moreira, Flora Martinez Figueira; Alencar Santos, Joyce; Kassuya, Candida Aparecida Leite; Croda, Julio Henrique Rosa; Cardoso, Claudia Andrea Lima; Vieira, Maria do Carmo; Góis Ruiz, Ana Lúcia Tasca; Ann Foglio, Mary; de Carvalho, João Ernesto; Formagio, Anelise Samara Nazari

    2017-08-24

    Leaves from Psidium guineense Sw. are used in popular medicine for the treatment of inflammatory disease. However, there is no scientific evidence demonstrating this activity. To evaluate the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of P. guineense and spathulenol (a major constituent). The study was conducted in part to provide evidence supporting the ethnobotanical use of the leaves of this species. The essential oil (EOPG) was extracted from the leaves of P. guineense by hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS). The major compound, spathulenol (PG-1), was isolated in a chromatographic column and characterized by nuclear magnetic resonance (NMR). EOPG and PG-1 were evaluated in vitro for antioxidant activity by DPPH, ABTS and MDA methods; anti-inflammatory potential was assessed using two models, including pleurisy and edema, in mice. The impact of EOPG and PG-1 on cell proliferation was determined via spectrophotometric quantification of the cellular protein content using a sulforhodamine B assay, and anti-Mycobacterium tuberculosis activity was determined using the REMA method. A total of 38 components were identified from the EOPG, with the sesquiterpenic alcohol spathulenol (PG-1) (80.7%) being the major constituent. EOPG and PG-1 exhibited the highest antioxidant activities in the DPPH and MDA system compared with reference standard, with IC50 values ranging from 26.13-85.60μg/mL. Oral administration of EOPG and PG-1 showed significant inhibition in the Cg-induced mice paw oedema and pleurisy model. The EOPG (GI50 = 0.89μg/mL) and PG-1 (GI50 = 49.30μg/mL) were particularly effective against the ovarian cancer cell line. Both showed moderate antimycobacterial activity. For the first time, this study demonstrated the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial properties of the essential oil of P. guineense (leaves were collected

  13. Synthesis and Antiproliferative Activity of Novel [1,2,4]Triazolo[1,5-a]pyrimidine-7-amine Derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHAI Xin; ZHANG Cun-long; HE Lei; LI Qi; WANG Jiu-liang; SHEN Xiao-li; GONG Ping

    2009-01-01

    ited the cell proliferation at a low concentration.Seven compounds,VI5,VI7,VI10,and VI12-VI15,possessed marked antiproliferative activity superior to that of cisplatin.of these seven initial hits,compound Vllo was the most active.

  14. An insight into synthetic Schiff bases revealing antiproliferative activities in vitro.

    Science.gov (United States)

    Sztanke, Krzysztof; Maziarka, Agata; Osinka, Anna; Sztanke, Małgorzata

    2013-07-01

    Schiff bases or azomethines are among the most important groups of biomolecules. These compounds have been found to reveal both remarkable biological activities and a variety of valuable practical applications. An interest in the exploration of novel series of synthetic Schiff bases has undoubtedly been growing due to their proven utility as attractive lead structures for the design of novel cytotoxic and cytostatic agents with a mechanism of action that sometimes differs from that of clinically authorized anticancer agents. Therefore, in the present paper we have focussed our attention on the collected synthetic simple Schiff bases of aldimine- and ketimine-types revealing anticancer activities in vitro, that have been described in the scientific literature during the last decade, and on structural variations whose affect the antiproliferative activity in sets of the designed molecules.

  15. Preselection of A- and B- modified d-homo lactone and d-seco androstane derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.

    Science.gov (United States)

    Kovačević, Strahinja Z; Podunavac-Kuzmanović, Sanja O; Jevrić, Lidija R; Vukić, Vladimir R; Savić, Marina P; Djurendić, Evgenija A

    2016-10-10

    The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d-homo lactone and d-seco androstane derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d-homo lactone and/or d-seco androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- (3) and 6α,7α-epoxy-1,4-dien-3-one (24) d-homo lactone androstane derivatives, as well as 4-en-3-one (15) d-seco androstane derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer - abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d-homo lactone and d-seco androstane derivatives with antiproliferative activity against breast and prostate cancer cells.

  16. Antiproliferative activity of New Zealand propolis and phenolic compounds vs human colorectal adenocarcinoma cells.

    Science.gov (United States)

    Catchpole, Owen; Mitchell, Kevin; Bloor, Stephen; Davis, Paul; Suddes, Amanda

    2015-10-01

    New Zealand propolis is a "European" type propolis obtained by honey bees mainly from exudates of poplar. European type propolis is known to have anti-inflammatory and anti-cancer properties and this activity has been attributed to some of the main constituents such as chrysin and CAPE (caffeic acid phenethyl ester). As part of our studies on how New Zealand propolis might benefit gastro-intestinal health, we carried out in vitro bioactivity-guided fractionation of "Bio30™" propolis using both anti-inflammatory (TNF-α, COX-1, COX-2) and anti-colon cancer (DLD-1 colon cancer cell viability) assays; and determined the phenolic compounds responsible for the activity. The New Zealand wax-free Bio30™ propolis tincture solids had very high levels of the dihydroflavonoids pinocembrin and pinobanksin-3-O-acetate, and high levels of the dimethylallyl, benzyl and 3-methyl-3-butenyl caffeates relative to CAPE. The DLD-1 assays identified strong anti-proliferative activity associated with these components as well as chrysin, galangin and CAPE and a number of lesser known or lower concentration compounds including benzyl ferulate, benzyl isoferulate, pinostrobin, 5-phenylpenta-2,4-dienoic acid and tectochrysin. The phenolic compounds pinocembrin, pinobanksin-3-O-acetate, tectochrysin, dimethylallyl caffeate, 3-methyl-3-butenyl caffeate, benzyl ferulate and benzyl isoferulate also showed good broad spectrum activity in anti-proliferative assays against three other gastro-intestinal cancer cell lines; HCT-116 colon carcinoma, KYSE-30 oesophageal squamous cancer, and NCI-N87 gastric carcinoma. Activity is also observed in anti-inflammatory assays although it appears to be limited to one of the first cytokines in the inflammatory cascade, TNF-α. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Antioxidant and antiproliferative activity of glycosides obtained by biotransformation of xanthohumol.

    Science.gov (United States)

    Tronina, Tomasz; Bartmańska, Agnieszka; Milczarek, Magdalena; Wietrzyk, Joanna; Popłoński, Jarosław; Rój, Edward; Huszcza, Ewa

    2013-04-01

    The biotransformation of xanthohumol (1), a prenylated chalcone isolated from hops by selected fungi, was investigated. Microbial regioselective glycosylation at the C-4' position led to xanthohumol 4'-O-β-d-glucopyranoside (2) and xanthohumol 4'-O-β-d-(4'''-O-methyl)-glucopyranoside (3). The subsequent cyclization of 2 resulted in isoxanthohumol 7-O-β-glucopyranoside (4). The structures of the products were identified based on spectroscopic methods. The biological activity of isolated metabolites has been evaluated. Compared to xanthohumol (1), metabolite 2 is a better 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenger, while 2 and 3 have stronger antiproliferative activity against the human HT-29 colon cancer cell line.

  18. Synthesis and antiproliferative activity of some A- and B modified D-homo lactone androstane derivatives

    Directory of Open Access Journals (Sweden)

    Savić Marina P.

    2013-01-01

    Full Text Available An efficient synthesis of several A- and B-modified D-homo lactone androstane derivatives from 3β-hydroxy-17-oxa-D-homoandrost-5-en-16-one (1 is reported. 17-Oxa-Dhomoandrost- 4-ene-3,16-dione (2, obtained by the Oppenauer oxidation of compound 1, was converted via the unstable intermediate 3,16-dioxo-4,17-dioxa-D-homoandrostane- 5α-carboxaldehyde (3 to 17-oxa-D-homo-3,5-seco-4-norandrostan-5-one-3-carboxylic acid (4, which was also obtained directly from compound 2. Compound 1 was acetylated to give 17-oxa-D-homoandrost-5-en-16-on-3β-yl acetate (5 which was then oxidized with chromium(VI-oxide in 50% acetic acid or with meta-chlorperbenzoic acid and chromium(VI-oxide to yield compounds 6-8 and 5α-hydroxy-17-oxa-D-homoandrostane- 6,16-dion-3β-yl acetate (9, respectively. The oximination of compound 9 gave a mixture of 6(E-hydroximino-5α-hydroxy-17-oxa-D-homoandrostan-16-on-3β-yl acetate (10 and 6(Z-hydroximino-5α-hydroxy-17-oxa-D-homoandrostan-16-on-3β-yl acetate (11, the hydrolysis of which gave 6(E-hydroximino-3β,5α-dihydroxy-17-oxa-D-homoandrostan- 16-one (12 and 6(Z-hydroximino-3β,5α-dihydroxy-17-oxa-D-homoandrostan-16-one (13. 6-Nitrile-17-oxa-5,6-seco-D-homoandrostane-5,16-dion-3β-yl acetate (14 was obtained under the Beckmann fragmentation of compounds 10 and 11. Only pure and stable compounds (1, 2, 4, 5, 9 and 14 were tested in vitro on six malignant cell lines (MCF-7, MDA-MB-231, PC-3, HeLa, HT-29, K562 and one non-tumor MRC-5 cell line. Significant antiproliferative activity against MDA-MB-231 cells showed compounds 1, 5 and 9, while compound 2 exhibited a strong antiproliferative activity. Only compound 14 showed weak antiproliferative activity against MCF-7 cells. All tested compounds were not toxic on MRC-5 cells, whereas Doxorubicin was highly toxic on these cells. [Projekat Ministarstva nauke Republike Srbije, br. 172021

  19. Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities

    Directory of Open Access Journals (Sweden)

    Abdulrahman I. Almansour

    2014-07-01

    Full Text Available A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E-arylmethylidene]tetrahydro-4(1H-pyridinones 2a–n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3 with N-methylglycine (sarcosine, phenylglycine, or proline. All compounds (50 μM were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231, leukemia lymphoblastic (CCRF-CEM, and ovarian carcinoma (SK-OV-3 cells. N-α-Phenyl substituted spiro-pyrrolidine derivatives (5a–n showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a–n, a number of derivatives including 6a–c and 6i–m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds in three classes, 6a, 6b, and 6m, were found to be the most potent derivatives showing 64%, 87%, and 74% antiproliferative activity in MDA-MB-231, SK-OV-3, and CCRF-CEM cells, respectively. Compound 6b showed an IC50 value of 3.6 mM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines.

  20. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    Directory of Open Access Journals (Sweden)

    Hui Guo

    2016-07-01

    Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

  1. Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities

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    Cristiane Santos Silva e Silva Figueiredo

    2017-05-01

    Full Text Available Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC and Minimal Bactericidal Concentration (MBC were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm. However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL. As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL. This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling. This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs. Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae

  2. New ursane triterpenoids from Salvia urmiensis Bunge: Absolute configuration and anti-proliferative activity.

    Science.gov (United States)

    Farimani, Mahdi Moridi; Bahadori, Mir Babak; Koulaei, Sheyda Ahmadi; Salehi, Peyman; Ebrahimi, Samad Nejad; Khavasi, Hamid Reza; Hamburger, Matthias

    2015-10-01

    Two new triterpenoids, urmiensolide B (1) and urmiensic acid (2), with rare carbon skeletons together with three known compounds were isolated from the aerial parts of Salvia urmiensis Bunge, an endemic species of Iran. The structures were established by a combination of 1D and 2D NMR, and HRESIMS, and in the case of 2 and 3, their structures were confirmed by single-crystal X-ray analysis. The absolute configuration of 2 was established by electronic circular dichroism (ECD) spectra. The new compounds were evaluated for their anti-proliferative activities against A549 and MCF-7 human cancer cell lines. Compounds 1 and 2 showed IC50 values of 2.8 and 1.6 μM against MCF-7 cells, respectively.

  3. The Synthesis and Antiproliferative Activities of New Arylidene-Hydrazinyl-Thiazole Derivatives

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    Adriana Grozav

    2014-12-01

    Full Text Available New and known arylidene-hydrazinyl-thiazole derivatives have been synthesized by a convenient Hantzsch condensation. All compounds were evaluated for their in vitro cytotoxicity on two carcinoma cell lines, MDA-MB231 and HeLa. Significant antiproliferative activity for 2-(2-benzyliden-hydrazinyl-4-methylthiazole on both MDA-MB-231 (IC50: 3.92 µg/mL and HeLa (IC50: 11.4 µg/mL cell lines, and for 2-[2-(4-methoxybenzylidene hydrazinyl]-4-phenylthiazole on HeLa (IC50: 11.1 µg/mL cell line is reported. Electrophoresis experiments showed no plasmid DNA (pTZ57R cleavage in the presence of the investigated thiazoles.

  4. Highly stable hexacoordinated nonoxidovanadium(IV) complexes of sterically constrained ligands: syntheses, structure, and study of antiproliferative and insulin mimetic activity.

    Science.gov (United States)

    Dash, Subhashree P; Pasayat, Sagarika; Bhakat, Saswati; Roy, Satabdi; Dinda, Rupam; Tiekink, Edward R T; Mukhopadhyay, Subhadip; Bhutia, Sujit K; Hardikar, Manasi R; Joshi, Bimba N; Patil, Yogesh P; Nethaji, M

    2013-12-16

    Three highly stable, hexacoordinated nonoxidovanadium(IV), V(IV)(L)2, complexes (1-3) have been isolated and structurally characterized with tridentate aroylhydrazonates containing ONO donor atoms. All the complexes are stable in the open air in the solid state as well as in solution, a phenomenon rarely observed in nonoxidovanadium(IV) complexes. The complexes have good solubility in organic solvents, permitting electrochemical and various spectroscopic investigations. The existence of nonoxidovanadium(IV) complexes was confirmed by elemental analysis, ESI mass spectroscopy, cyclic voltammetry, EPR, and magnetic susceptibility measurements. X-ray crystallography showed the N3O3 donor set to define a trigonal prismatic geometry in each case. All the complexes show in vitro insulin mimetic activity against insulin responsive L6 myoblast cells, with complex 3 being the most potent, which is comparable to insulin at the complex concentration of 4 μM, while the others have moderate insulin mimetic activity. In addition, the in vitro antiproliferative activity of complexes 1-3 against the HeLa cell line was assayed. The cytotoxicity of the complexes is affected by the various functional groups attached to the bezoylhydrazone derivative and 2 showed considerable antiproliferative activity compared to the most commonly used chemotherapeutic drugs.

  5. The Antiproliferative Activity of Sclerotia of Lignosus rhinocerus (Tiger Milk Mushroom).

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    Lee, M L; Tan, N H; Fung, S Y; Tan, C S; Ng, S T

    2012-01-01

    Lignosus rhinocerus, the tiger milk mushroom, is one of the most important medicinal mushrooms used by the indigenous people of Southeast Asia and China. It has been used to treat breast cancer. A cold water extract (LR-CW) prepared from the sclerotia of L. rhinocerus cultivar was found to exhibit antiproliferative activity against human breast carcinoma (MCF-7) and human lung carcinoma (A549), with IC(50) of 96.7 μg/mL and 466.7 μg/mL, respectively. In comparison, LR-CW did not show significant cytotoxicity against the two corresponding human normal cells, 184B5 (human breast cell) and NL 20 (human lung cell). DNA fragmentation studies suggested that the cytotoxic action of LR-CW against cancer cells is mediated by apoptosis. Sephadex G-50 gel filtration fractionation of LR-CW yielded a high-molecular-weight and a low-molecular-weight fraction. The high-molecular-weight fraction contains mainly carbohydrate (68.7%) and small amount of protein (3.6%), whereas the low-molecular-weight fraction contains 31% carbohydrate and was devoid of protein. Only the high-molecular-weight fraction exhibited antiproliferative activity against cancer cells, with IC(50) of 70.0 μg/mL and 76.7 μg/mL, respectively. Thus, the cytotoxic action of the LR-CW is due to the high-molecular-weight fraction, either the proteins or protein-carbohydrate complex.

  6. The Antiproliferative Activity of Sclerotia of Lignosus rhinocerus (Tiger Milk Mushroom

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    M. L. Lee

    2012-01-01

    Full Text Available Lignosus rhinocerus, the tiger milk mushroom, is one of the most important medicinal mushrooms used by the indigenous people of Southeast Asia and China. It has been used to treat breast cancer. A cold water extract (LR-CW prepared from the sclerotia of L. rhinocerus cultivar was found to exhibit antiproliferative activity against human breast carcinoma (MCF-7 and human lung carcinoma (A549, with IC50 of 96.7 μg/mL and 466.7 μg/mL, respectively. In comparison, LR-CW did not show significant cytotoxicity against the two corresponding human normal cells, 184B5 (human breast cell and NL 20 (human lung cell. DNA fragmentation studies suggested that the cytotoxic action of LR-CW against cancer cells is mediated by apoptosis. Sephadex G-50 gel filtration fractionation of LR-CW yielded a high-molecular-weight and a low-molecular-weight fraction. The high-molecular-weight fraction contains mainly carbohydrate (68.7% and small amount of protein (3.6%, whereas the low-molecular-weight fraction contains 31% carbohydrate and was devoid of protein. Only the high-molecular-weight fraction exhibited antiproliferative activity against cancer cells, with IC50 of 70.0 μg/mL and 76.7 μg/mL, respectively. Thus, the cytotoxic action of the LR-CW is due to the high-molecular-weight fraction, either the proteins or protein-carbohydrate complex.

  7. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships.

    Science.gov (United States)

    Gnabre, John; Unlu, Irem; Chang, Tso-Cheng; Lisseck, Paul; Bourne, Bryan; Scolnik, Ryan; Jacobsen, Neil E; Bates, Robert; Huang, Ru Chih

    2010-10-15

    Separate benzocyclooctadiene lignans were isolated from the berries of Schisandra chinensis in milligram quantities on analytical reverse phase (RP) HPLC by an automated repeat-injection method and shown to have anti-proliferative activity against human colorectal cancer cells. Structures of the compounds were determined by a combination of NMR and mass spectrometry. Stereospecific NMR assignments for gomisin-N and deoxyschisandrin, gave more complete and accurate data than previously reported, based on 600MHz 2D HSQC, DQF-COSY and HMBC data. Comparison of coupling constants and HMBC crosspeak intensities with calculated and X-ray crystal structures confirmed their stereochemistry and conformation. Analysis of structure-activity relationships revealed the importance of key structural determinants. The S-biphenyl configuration of gomisin N, the most active lignan, correlated with increased anti-proliferative activity, while the presence of a hydroxyl group at the C7 position reduced or abolished this activity. Increased activity was also observed when a methylenedioxy group was present between C12 and C13. The percent yield of the most active compounds relative to the starting plant materials was 0.0156% for deoxyschisandrin and 0.0173% for gomisin N. The results of these studies indicate that automated repeat-injection method of analytical HPLC may provide a superior alternative to the standard semi-preparative HPLC techniques for separation of complex mixtures.

  8. Free radical scavenging property and antiproliferative activity of Rhodiola imbricata Edgew extracts in HT-29 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ravichandran Senthilkumar; Thangaraj Parimelazhagan; Om Prakash Chaurasia; RB Srivastava

    2013-01-01

    Objective: To investigate the in vitro antioxidant and antiproliferative activity of rhizome extracts of Rhodiola imbricata (R. imbricata) in HT-29 human colon cancer cell line. Methods: The successively extracted rhizome of R. imbricata using various solvents was analyzed for their total phenolics, tannins and flavonoid contents. In vitro antioxidant activity was evaluated by employing different assays, including DPPH, ABTS radical scavenging assays, FRAP, phosphomolybdenum reduction assay, superoxide anion, hydroxyl radical scavenging activities and metal chelating ability. Results: Acetone and methanol extracts recorded higher phenolic content and showed comparable antioxidant activity with standard reference. Additionally, they also inhibited the proliferation of HT-29 cells upon treatment at higher concentration (200 μg/mL) (acetone and methanol, 84% and 84%, respectively). On examination acetone extract exhibited antiproliferative activity in a concentration dependent manner whereas, methanol extract showed both dose dependent and time dependent inhibitory activity. Conclusions: The results obtained justify the traditional usage of R. imbricata from their promising antioxidant activity.

  9. In vitro anti-proliferative activity of clove extract on human gastric carcinoma

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    A. Karimi

    2017-10-01

    Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

  10. A homotetrameric agglutinin with antiproliferative and mitogenic activities from haricot beans.

    Science.gov (United States)

    Ho Wong, Jack; Ng, T B

    2005-12-15

    A homotetrameric agglutinin with a molecular mass of 130 kDa was isolated from seeds of the haricot bean. The agglutinin was isolated using a procedure that involved ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel and gel filtration by fast protein liquid chromatography on Superdex 200. Haricot bean agglutinin was adsorbed on DEAE-cellulose and Affi-gel blue gel. The hemagglutinating activity of the agglutinin was stable up to 40 degrees C. It underwent a 40% decline when the temperature was raised to 50 degrees C and a complete loss when the temperature was further increased to 80 degrees C. The hemagglutinating activity exhibited a time-dependent loss in activity when the agglutinin was incubated at 100 degrees C for different durations. No activity was discernible when the agglutinin was left at 100 degrees C for 1 min. The activity also underwent a decline in the presence of 500 mM FeCl(3) and CaCl(2). Haricot bean agglutinin manifested a weaker mitogenic activity than concanavalin A toward mouse splenocytes. It exhibited antiproliferative activity toward the tumor cell lines M1 [leukemia], HepG2 [hepatoma] and L1210 [leukemia] cells.

  11. The antioxidant and antiproliferative activities of methanolic extracts from Njavara rice bran

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    Babu Phanithi P

    2010-01-01

    Full Text Available Abstract Background Free radical-induced oxidative stress is the root cause for many human diseases. Naturally occurring antioxidant supplements from plants are vital to counter the oxidative damage in cells. The main objective of the present study was to characterize the antioxidant and antiproliferative potential of rice bran extracted from an important Indian rice variety, Njavara and to compare the same with two commercially available basmati rice varieties: Vasumathi, Yamini and a non medicinal variety, Jyothi. Methods Methanolic extracts of rice bran from four varieties; Vasumathi, Yamini, Jyothi and Njavara were used to study their total phenolic and flavonoid contents, in vitro antioxidant activities including total antioxidant activity, scavenging of nitric oxide and 1,1-Diphenyl-2-picrylhydrazyl (DPPH radical, reducing power and cytotoxic activity in C6 glioma cells. Correlation coefficient and regression analysis were done by using Sigmastat version 3.1 and Stata statistical package respectively. Results Rice bran methanolic extract from Njavara showed the highest antioxidant and cell cytotoxic properties compared to the other three rice varieties. IC50 values for scavenging DPPH and nitric oxide were in the range of 30.85-87.72 μg/ml and 52.25-107.18 μg/ml respectively. Total antioxidant activity and reducing power were increased with increasing amounts of the extract. Total phenolic and flavonoid contents were in the range of 3.2-12.4 mg gallic acid-equivalent (GAE/g bran and 1.68-8.5 mg quercetin-equivalent (QEE/g bran respectively. IC50 values of cytotoxic assay (MTT assay were 17.53-57.78 μg/ml. Correlation coefficient and regression analysis of phenolic content with DPPH and NO scavenging, MTT (-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay, total antioxidant assay and reducing power showed a highly significant correlation coefficient values (96-99% and regression values (91-98%. Conclusion The results of

  12. Antiproliferative and Antiestrogenic Activities of Bonediol an Alkyl Catechol from Bonellia macrocarpa

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    Rosa Moo-Puc

    2015-01-01

    Full Text Available The purpose of this study was to investigate antiproliferative activity of bonediol, an alkyl catechol isolated from the Mayan medicinal plant Bonellia macrocarpa. Bonediol was assessed for growth inhibition of androgen-sensitive (LNCaP, androgen-insensitive (PC-3, and metastatic androgen-insensitive (PC-3M human prostate tumor cells; toxicity on normal cell line (HEK 293 was also evaluated. Hedgehog pathway was evaluated and competitive 3H-estradiol ligand binding assay was performed. Additionally, antioxidant activity on Nrf2-ARE pathway was evaluated. Bonediol induced a growth inhibition on prostate cancer cell lines (IC50 from 8.5 to 20.6 µM. Interestingly, bonediol binds to both estrogen receptors (ERα (2.5 µM and ERβ (2.1 µM and displaces the native ligand E2 (17β-estradiol. No significant activity was found in the Hedgehog pathway. Additionally, activity of bonediol on Nrf2-ARE pathway suggested that bonediol could induce oxidative stress and activation of detoxification enzymes at 1 µM (3.8-fold. We propose that the compound bonediol may serve as a potential chemopreventive treatment with therapeutic potential against prostate cancer.

  13. Antiproliferative activity and apoptotic effects of Filipendula ulmaria pollen against C26 mice colon tumour cells

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    Mărgăoan Rodica

    2016-06-01

    Full Text Available Honeybee collected pollen exhibits high nutritional and pharmaceutical benefits for the human diet and medicine. Pollen’s antioxidant, anti-ageing, anti-inflammatory, anti-atherosclerosis, and cardioprotective activity, depending on the floral origin, are well known. Recent studies proposed that pollen may also be an excellent cancer-fighting candidate, as pollen harbours high amounts of phenolic substances. In our study, Filipendula ulmaria pollen (bee collected was methanol-water extracted and used to verify its in vitro pharmacological activities on C26 mice cancer tumour cells. Three different concentrations of the extract were tested in antitumour assays. Monitoring was done after 6, 12, 24, and 48 hours. Promising results were obtained for antiproliferative and apoptotic activity of the pollen extracts, with high efficiency for the highest concentration (1 mg/mL. For both activities, time and concentration-dependent effects were observed. Pollen extracts or bee collected pollen has a high potential as an antitumour agent for use in human medicine, because they are both rich in bioactive compounds.

  14. Antiproliferative Activity Evaluation of a Series of N-1,3-Benzothiazol-2-ylbenzamides as Novel Apoptosis Inducers

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    Filomena Corbo

    2016-01-01

    Full Text Available A series of N-1,3-benzothiazol-2-ylbenzamide derivatives were studied for their antiproliferative activity on human liver hepatocellular carcinoma (HepG2 and human breast cancer (MCF-7 cell lines. Most of them were found to show a prominent inhibitory effect on cell growth. Among the most active compounds, 1k emerged for its proapoptotic effect that is particularly evident towards MCF-7 cancer cell lines.

  15. Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity.

    Science.gov (United States)

    Parrino, Barbara; Carbone, Anna; Spanò, Virginia; Montalbano, Alessandra; Giallombardo, Daniele; Barraja, Paola; Attanzio, Alessandro; Tesoriere, Luisa; Sissi, Claudia; Palumbo, Manlio; Cirrincione, Girolamo; Diana, Patrizia

    2015-04-13

    Three new ring systems, pyrido[2',3':3,4]pyrrolo[1,2-a]quinoxalines, pyrido[3',2':3,4]pyrrolo[1,2-a]quinoxalines and pyrido[2',3':5,6]pyrazino[2,1-a]isoindoles, were synthesized through an aza-substitution on the already active isoindolo-quinoxaline system and in particular in the position 7 or 4 of the isoindole moiety and in position 5 of the quinoxaline portion. All new compounds were screened by the National Cancer Institute (Bethesda, MD) against a panel of 60 human tumor cell lines. Biological results of the most active derivatives, with pGI50 values between 7.09 and 7.27, confirmed the importance of the presence of methoxy substituents for biological activity. The anti-proliferative effect of selected quinoxalines was associated with apoptosis of the cells and arrest in G2/M phase of the cell cycle. DNA binding properties of the compounds was also assessed to investigate the possible mechanism of action.

  16. Antiproliferative activity of three methoxylated flavonoids isolated from Zeyheria montana Mart. (Bignoniaceae) leaves.

    Science.gov (United States)

    Seito, Leonardo Noboru; Ruiz, Ana Lucia Tasca Goiz; Vendramini-Costa, Debora; Tinti, Sirlene Valério; de Carvalho, João Ernesto; Bastos, Jairo Kenupp; Di Stasi, Luiz Claudio

    2011-10-01

    The present study isolated three major active flavonoids, two flavones named 4',5,7-trimethoxy-luteolin (1) and 6-hydroxy-5,7-dimethoxyflavone (2) and the flavanone 5-hydroxy-6,7-dimethoxyflavanone (3) from Zeyheria montana dichloromethane leaf extract. Isolation and purification were conducted with the application of column chromatography and structures were assigned by spectral analysis. All compounds were evaluated for cytotoxic activities against human tumor cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-ADR/RES (breast expressing phenotype multiple drug resistance), 786-0 (renal), NCI-H460 (lung, non-small cells), PC-3 (prostate), OVCAR-3 (ovarian), HT-29 (colon) and K562 (leukemia) in vitro. All compounds were active in different degrees on several tumor cell lines and flavanone 3 showed cytotoxicity against almost all cell lines, particularly against human NCI-ADR/RES and K562 cell lines. In conclusion, three antiproliferative compounds were isolated for the first time from Zeyheria montana and its leaves were characterized as an important source of methoxylated flavones and flavanone as potential antitumor compounds. Copyright © 2011 John Wiley & Sons, Ltd.

  17. Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides.

    Science.gov (United States)

    Raffa, Demetrio; Maggio, Benedetta; Cascioferro, Stella; Raimondi, Maria Valeria; Schillaci, Domenico; Gallo, Giorgio; Daidone, Giuseppe; Plescia, Salvatore; Meneghetti, Fiorella; Bombieri, Gabriella; Di Cristina, Antonietta; Pipitone, Rosaria M; Grimaudo, Stefania; Tolomeo, Manlio

    2009-01-01

    A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1 microM (0.0153 microM in SR leukemia) causing a block in G0-G1 phase of cell cycle. Analysis of pRb expression showed that these two compounds increased the ratio between underphosphorylated pRb and total pRb. The X-ray structure of 10w, confirmed the 3-amino-N-phenyl-1H-indazole-1-carboxamide structure of compounds 10.

  18. Synthesis, Antiproliferative and Antifungal Activities of 1,2,3-Triazole-Substituted Carnosic Acid and Carnosol Derivatives

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    Mariano Walter Pertino

    2015-05-01

    Full Text Available Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1–3 were the most active antiproliferative compounds of the series, with IC50 values in the range of 43.4–46.9 μM and 39.2–48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL−1. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition at 250 µg∙mL−1 In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL−1.

  19. Antiproliferative activity of O4-benzo[c]phenanthridine alkaloids against HCT-116 and HL-60 tumor cells.

    Science.gov (United States)

    Hatae, Noriyuki; Fujita, Erina; Shigenobu, Saori; Shimoyama, Sayumi; Ishihara, Yuhsuke; Kurata, Yuhki; Choshi, Tominari; Nishiyama, Takashi; Okada, Chiaki; Hibino, Satoshi

    2015-07-15

    The O4-benzo[c]phenanthridine alkaloids exhibit potent antiproliferative activity against cancer cells, which is derived from their ability to inhibit of topoisomerase I and II. It has been reported that in the alkaloids a cationic quaternary ammonium atom, which results in resonance effects between ring A and B, is necessary for increased antiproliferative activity. These findings indicate the role of their substituents at ring A on inhibition of tumor cell proliferation. In the present study, we systematically assessed the cytotoxic activities of naturally occurring alkaloids and their derivatives containing various ring A substituents against two tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. Among the cationic iminium alkaloids, which displayed more potent activity than the corresponding neutral derivatives, and the 7,8-oxygenated benzo[c]phenanthridine alkaloids, chelerythrine and NK109, exhibited stronger antiproliferative activity than the 8,9- and 9,10-oxygenated alkaloids. The activity of cationic iminium alkaloids could be correlated with the bond lengths of their ring A substituents and the electrostatic potentials of their ammonium molecules by DFT calculation.

  20. Evaluation of antiproliferative and anti-inflammatory activities of methanol extract and its fractions from the Mediterranean sponge

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    Dellai Afef

    2012-05-01

    Full Text Available Abstract Background Without doubt, natural products have been, and still are, the cornerstone of the health care armamentarium. Of all natural sources, the marine environment is clearly the last great frontier for pharmaceutical and medical research. Methods This work progresses in the direction of identifying component(s from the Mediterranean sponge, Spongia officinalis with pharmacological activities. In the present study we investigated the efficacy of methanol extract and its semi-purified fractions (F2, F3 from Spongia officinalis for their in vivo anti-inflammatory activity using the carrageenan-induced paw edema in rats and their in vitro antiproliferative effects by their potential cytotoxic activity using the MTT colorimetric method and clonogenic inhibition against three human cancer cell lines (A549, lung cell carcinoma, HCT15, colon cell carcinoma and MCF7, breast adenocarcinoma. Results The fractions F2 and F3 showed interesting anti-inflammatory and antiproliferative activities in a dose dependent manner. Conclusions The present study indicates that the methanolic extrac and its fractions from Spongia officinalis are a significant source of compounds with the antiproliferative and anti-inflammatory activities, and this may be useful for developing potential chemopreventive substances.

  1. Antiproliferative activity of VLC fractions obtained from Asparagopsis armata associated bacteria

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    João Fonseca Francisco

    2014-06-01

    Full Text Available Many studies are showing the presence of bioactive compounds in marine organisms, such as algae and algae associated bacteria. Cancer is one of the major causes of death in the world, consequently research for new antitumor compounds is continuous and have high importance for the human health. The aim of this study was to evaluate the antitumor activity of Shewanella sp. associated bacteria from Asparagopsis armata. Crude extract of associated bacteria was obtained with methanol and dichloromethane (1:1 extraction. Then the crude extract was fractioned by vacuum liquid chromatography (VLC using cyclohexane with increasing amounts of 25% of ethyl acetate, in order to isolate different compounds obtained five fractions (F1-F5. The cell viability and the cell proliferation studies were performed on human breast adenocarcinoma cell line (MCF-7 cells according to MTT method. In cytotoxicity assay (1mg/ml; 24 hours, the highest reduction of MCF-7 viability was induced by F2 and F3 fractions (53.6% and 48.6% respectively. On the other hand in cell proliferation assay (1mg/ml; 24 hours, all fractions showed anti-proliferative activity (1mg/mL, however the highest inhibition of MCF-7 proliferation was exhibited by F3 and F5 fractions, 15% and 17,7%, respectively. These results suggest that the Shewanella sp. associated bacteria from Asparagopsis armata can be an interesting source of new antitumor drugs.

  2. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.

    Science.gov (United States)

    Lopez-Girona, A; Mendy, D; Ito, T; Miller, K; Gandhi, A K; Kang, J; Karasawa, S; Carmel, G; Jackson, P; Abbasian, M; Mahmoudi, A; Cathers, B; Rychak, E; Gaidarova, S; Chen, R; Schafer, P H; Handa, H; Daniel, T O; Evans, J F; Chopra, R

    2012-11-01

    Thalidomide and the immunomodulatory drug, lenalidomide, are therapeutically active in hematological malignancies. The ubiquitously expressed E3 ligase protein cereblon (CRBN) has been identified as the primary teratogenic target of thalidomide. Our studies demonstrate that thalidomide, lenalidomide and another immunomodulatory drug, pomalidomide, bound endogenous CRBN and recombinant CRBN-DNA damage binding protein-1 (DDB1) complexes. CRBN mediated antiproliferative activities of lenalidomide and pomalidomide in myeloma cells, as well as lenalidomide- and pomalidomide-induced cytokine production in T cells. Lenalidomide and pomalidomide inhibited autoubiquitination of CRBN in HEK293T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplified pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for lenalidomide resistance in H929 myeloma cell lines was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to both pomalidomide and lenalidomide, CRBN protein was undetectable. Our biophysical, biochemical and gene silencing studies show that CRBN is a proximate, therapeutically important molecular target of lenalidomide and pomalidomide.

  3. Antiproliferative activity of Eremanthus crotonoides extracts and centratherin demonstrated in brain tumor cell lines

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    Jonathas F. R. Lobo

    2012-12-01

    Full Text Available The genus Eremanthus is recognized by the predominance of sesquiterpene lactones from the furanoheliangolide type, a class of substances extensively tested against cancer cell lines. Thus, the species E. crotonoides (DC. Sch. Bip., Asteraceae, obtained on "restinga" vegetation was evaluated against U251 and U87-MG glioma cell lines using the MTT colorimetric assay. Dichloromethane fraction was cytotoxic to both glioblastoma multiforme cell lines. We then conducted UPLC-PDA-ESI-MS/MS analysis of the dichloromethane fraction, which allowed the identification of the sesquiterpene lactones centratherin and goyazensolide. The isolation of centratherin was performed using chromatographic techniques and the identification of this substance was confirmed according to NMR data. Cytotoxic activity of centratherin alone was also evaluated against both U251 and U87-MG cells, which showed IC50 values comparable with those obtained for the commercial anticancer drug doxorubicin. All the tested samples showed cytotoxic activity against glioblastoma multiforme cells which suggests that E. crotonoides extracts may be important sources of antiproliferative substances and that the centratherin may serve as prototype for developing new antiglioblastoma drugs.

  4. Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines.

    Science.gov (United States)

    Nguyen, Van-Son; Shi, Ling; Luan, Fang-Qian; Wang, Qiu-An

    2015-01-01

    Kaempferide (3,5,7-trihydroxy-4'-methoxyflavone, 1), a naturally occurring flavonoid with potent anticancer activity in a number of human tumour cell lines, was first semisynthesized from naringin. Based on Mannich reaction of kaempferide with various secondary amines and formaldehyde, nine novel kaempferide Mannich base derivatives 2-10 were synthesized. The aminomethylation occurred preferentially in the position at C-6 and C-8 of the A-ring of kaempferide. All the synthetic compounds were tested for antiproliferative activity against three human cancer cell lines (Hela, HCC1954, SK-OV-3) by the standard MTT method. The results showed that compounds 1, 2 and 5-10 were more potent against Hela cells with IC50 values of 12.47-28.24 μM than the positive control cis-platin (IC50 41.25 μM), compounds 5, 6, 8 and 10 were more potent against HCC1954 cells with IC50 values of 8.82-14.97 μM than the positive control cis-platin (IC50 29.68 μM), and compounds 2, 3, 5, 6 and 10 were more potent against SK-OV-3 cells with IC50 values of 7.67-18.50 μM than the positive control cis-platin (IC50 21.27 μM).

  5. Discovery of autophagy inhibitors with antiproliferative activity in lung and pancreatic cancer cells.

    Science.gov (United States)

    Nordstrøm, Lars Ulrik; Sironi, Juan; Aranda, Evelyn; Maisonet, Jorge; Perez-Soler, Roman; Wu, Peng; Schwartz, Edward L

    2015-02-12

    The autophagy inhibitors chloroquine (CQ) and hydroxychloroquine (HCQ) have single agent antiproliferative activity against human cancer cell lines; however, low potency may limit their antitumor efficacy clinically. We synthesized a series of chloroquine analogs that retained the 4-aminoquinoline subunit and incorporated different substituted triazoles into the target structure. These compounds were tested for growth inhibition against H460 and HCC827 human lung cancer and BxPC3 pancreatic cancer cells. The most potent compound, EAD1, had an IC50 of 5.8 μM in the BxPC3 cells and was approximately 8-fold more potent than CQ and HCQ. EAD1 inhibited autophagy, as judged by the cellular accumulation of the autophagy-related autophagosome proteins LC3-II and p62 and induced apoptosis. The increases in LC3-II levels by the analogues were highly correlated with their growth inhibitory IC50s, suggesting that autophagy blockade is closely linked to inhibition of cell proliferation. EAD1 is a viable lead compound for evaluation of the antitumor activity of autophagy inhibitors in vivo.

  6. Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ramaswamy Nagarajan

    2008-11-01

    Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

  7. New chalcone and pterocarpoid derivatives from the roots of Flemingia philippinensis with antiproliferative activity and apoptosis-inducing property.

    Science.gov (United States)

    Kang, Wen-Jia; Li, Da-Hong; Han, Tong; Sun, Lin; Fu, Yan-Bin; Sai, Chun-Mei; Li, Zhan-Lin; Hua, Hui-Ming

    2016-07-01

    Investigation of the roots of Flemingia philippinensis resulted in the isolation of two new chalcones, flemiphilippinones B (1) and C (2), and one new pterocarpoid, demethylwedelolactone-11-methyl ether (3), together with 12 known compounds (4-15). The antiproliferative activity against PC-3 cells was evaluated and most compounds showed cytotoxicity, among which, compound 2 exhibited GI50 value of 14.12μM. The antiproliferative activity of 2 against Bel-7402 and CaEs-17 cells was also measured, with GI50 values of 1.91 and 2.58μM, respectively. Intensive mechanism study showed that 2 caused cell-cycle arrest at S/G2 phase and induced apoptosis in Bel-7402 cells through mitochondria-related pathway.

  8. Benzo[f]azino[2,1-a]phthalazinium cations: novel DNA intercalating chromophores with antiproliferative activity.

    Science.gov (United States)

    Martínez, Valentín; Burgos, Carolina; Alvarez-Builla, Julio; Fernández, Gerónimo; Domingo, Alberto; García-Nieto, Raquel; Gago, Federico; Manzanares, Ignacio; Cuevas, Carmen; Vaquero, Juan J

    2004-02-26

    New azaquinolizinium-type cations have been obtained from isochromane. The synthesis was completed over seven steps and included as the key feature an intramolecular Westphal condensation. This first example of the intramolecular process allowed the preparation of benzo[f]pyrido[2,1-a]phthalazinium and benzo[f]quino[2,1-a]phthalazinium salts, which were evaluated as DNA intercalators, DNA topoisomerase I inhibitors, and antiproliferative compounds. Both cationic systems behave as DNA intercalators and exhibit antiproliferative activity. The pentacyclic benzo[f]quino[2,1-a]phthalazinium cations also have an inhibitory effect on the catalytic activity of DNA topoisomerase I, without trapping of cleavage complexes. Structural characterization using density functional theory indicates that the fused ring systems are slightly nonplanar, and additional molecular modeling studies suggest a preferred orientation for the intercalating chromophores within a typical CpG or TpG intercalation site.

  9. Pulsed electric field processing preserves the antiproliferative activity of the milk fat globule membrane on colon carcinoma cells.

    Science.gov (United States)

    Xu, S; Walkling-Ribeiro, M; Griffiths, M W; Corredig, M

    2015-05-01

    The present work evaluated the effect of processing on the antiproliferative activities of milk fat globule membrane (MFGM) extracts. The antiproliferative activity on human adenocarcinoma HT-29 cells of untreated MFGM extracts were compared with those extracted from pasteurized cream, thermally treated cream, or cream subjected to pulsed electrical field (PEF) processing. The PEF with a 37 kV/cm field strength applied for 1,705μs at 50 and 65°C was applied to untreated cream collected from a local dairy. Heating at 50 or 65°C for 3min (the passage time in the PEF chamber) was also tested to evaluate the heating effect during PEF treatments. The MFGM extracted from pasteurized cream did not show an antiproliferative activity. On the other hand, isolates from PEF-treated cream showed activity similar to that of untreated samples. It was also shown that PEF induced interactions between β-lactoglobulin and MFGM proteins at 65°C, whereas the phospholipid composition remained unaltered. This work demonstrates the potential of PEF not only a means to produce a microbiologically safe product, but also as a process preserving the biofunctionality of the MFGM.

  10. Antioxidant and Antiproliferative Activities of Heated Sterilized Pepsin Hydrolysate Derived from Half-Fin Anchovy (Setipinna taty

    Directory of Open Access Journals (Sweden)

    Dongfeng Wang

    2011-06-01

    Full Text Available In this paper we studied the antioxidant and antiproliferative activities of the heated pepsin hydrolysate from a marine fish half-fin anchovy (HAHp-H. Furthermore, we compared the chemical profiles including the amino acid composition, the browning intensity, the IR and UV-visible spectra, and the molecular weight distribution between the half-fin anchovy pepsin hydrolysate (HAHp and HAHp-H. Results showed that heat sterilization on HAHp improved the 1,1-diphenyl-2-picryl-hydrazil (DPPH radical-scavenging activity and reducing power. In addition, the antiproliferative activities were all increased for HAHp-H on DU-145 human prostate cancer cell line, 1299 human lung cancer cell line and 109 human esophagus cancer cell line. The contents of free amino acid and reducing sugar of HAHp-H were decreased (P < 0.05. However, hydrophobic amino acid residues and the browning intensity of HAHp-H were increased. FT-IR spectroscopy indicated that amide I and amide III bands of HAHp-H were slightly modified, whereas band intensity of amide II was reduced dramatically. Thermal sterilization resulted in the increased fractions of HAHp-H with molecular weight of 3000–5000 Da and below 500 Da. The enhanced antioxidant and antiproliferative activities of HAHp-H might be attributed to the Maillard reaction.

  11. Evaluation of the Antioxidant Activity and Antiproliferative Effect of the Jaboticaba (Myrciaria cauliflora Seed Extracts in Oral Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Wen-Hung Wang

    2014-01-01

    Full Text Available It is becoming increasingly evident that certain phytochemicals possess cancer chemopreventive properties. In this study, the antiproliferative activity of extracts from different parts of the jaboticaba (Myrciaria cauliflora plant was evaluated for its effect on human oral carcinoma cell lines. The cytotoxicities of various plant extract concentrations were examined and the 50% maximal inhibitory concentration (IC50 was determined. Water extracts of jaboticaba seeds showed concentration-dependent antiproliferative effects. Annexin V/propidium iodide positivity with active caspase-3 induction indicated that the treated cells underwent apoptosis. Several important regulatory proteins (Bcl-2, Bcl-xL, Bid, and survivin involved in apoptosis were also evaluated. The antioxidant activity of jaboticaba was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS assays, and the drug concentration eliciting 50% maximum stimulation (SC50 was determined. The present findings suggest that water extracts of jaboticaba seeds exhibit an antiproliferative effect against oral cancer cells by inducing apoptosis through downregulating survivin expression and thereby activating caspase-mediated Bid cleavage.

  12. NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins

    Directory of Open Access Journals (Sweden)

    Dahong Li

    2016-09-01

    Full Text Available A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO donor hybrids (10a–i were designed and synthesized from commercially available oridonin (1. These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC50 of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10a–i also showed cytotoxic selectivity between tumor and normal liver cells with IC50 ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations.

  13. Isolation and antiproliferative activity of Lotus corniculatus lectin towards human tumour cell lines.

    Science.gov (United States)

    Rafiq, Shaista; Majeed, Rabiya; Qazi, Asif Khurshid; Ganai, Bashir Ahmad; Wani, Ishfak; Rakhshanda, Syed; Qurishi, Yasrib; Sharma, P R; Hamid, Abid; Masood, Akbar; Hamid, Rabia

    2013-12-15

    The objective of the study was to investigate the anti cancer activity of a lectin isolated from Lotus corniculatus seeds. A tetrameric 70kDa galactose specific lectin was purified using two step simple purification protocol which involved affinity chromatography on AF-BlueHC650M and gel filtration on Sephadex G-100. The lectin was adsorbed on AF-BlueHC650M and desorbed using 1M NaCl in the starting buffer. Gel filtration on Sephadex G-100 yielded a major peak absorbance that gave two bands of 15kDa and 20kDa in SDS PAGE. Hemagglutination activity was completely preserved, when the temperature was in the range of 20-60°C. However, drastic reduction in activity occurred at temperatures above 60°C. Full hemagglutination activity was retained at ambient pH 4-12. Thereafter no activity was observed above pH 13. Hemaglutination of the lectin was inhibited by d-galactose. The lectin showed a strong antiproliferative activity towards human leukemic (THP-1) cancer cells followed by lung cancer (HOP62) cells and HCT116 with an IC50 of 39μg/ml and 50μg/ml and 60μg/ml respectively. Flow cytometry analysis showed an increase in the percentage of cells in sub G0G1 phase confirming that Lotus corniculatus lectin induced apoptosis. Morphological observations showed that Lotus corniculatus lectin (LCL) treated THP-1 cells displayed apparent apoptosis characteristics such as nuclear fragmentation, appearance of membrane enclosed apoptotic bodies and DNA fragmentation. Lotus corniculatus lectin (LCL) effectively inhibits the cell migration in a dose dependent manner as indicated by the wound healing assay.

  14. ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action.

    Science.gov (United States)

    Fletcher, Graham C; Brokx, Richard D; Denny, Trisha A; Hembrough, Todd A; Plum, Stacy M; Fogler, William E; Sidor, Carolyn F; Bray, Mark R

    2011-01-01

    ENMD-2076 is a novel orally active, small molecule kinase inhibitor with a mechanism of action involving several pathways key to tumor growth and survival: angiogenesis, proliferation, and the cell cycle. ENMD-2076 has selective activity against the mitotic kinase Aurora A, as well as kinases involved in angiogenesis (VEGFRs, FGFRs). ENMD-2076 inhibited the growth in vitro of a wide range of human solid tumor and hematopoietic cancer cell lines with IC(50) values ranging from 0.025 to 0.7 μmol/L. ENMD-2076 was also shown to induce regression or complete inhibition of tumor growth in vivo at well-tolerated doses in tumor xenograft models derived from breast, colon, melanoma, leukemia, and multiple myeloma cell lines. Pharmacodynamic experiments in vivo showed that in addition to inhibiting Aurora A, single doses of ENMD-2076 had sustained inhibitory effects on the activation of Flt3 as well as the angiogenic tyrosine kinases, VEGFR2/KDR and FGFR1 and 2. ENMD-2076 was shown to prevent the formation of new blood vessels and regress formed vessels in vivo at doses equivalent to those that gave substantial activity in tumor xenograft models. These results indicate that ENMD-2076 is a well-tolerated, orally active multitarget kinase inhibitor with a unique antiangiogenic/antiproliferative profile and provides strong preclinical support for use as a therapeutic for human cancers. Several phase 1 studies involving ENMD-2076 have been recently completed, and the compound is currently being evaluated in a phase 2 clinical trial in patients with platinum-resistant ovarian cancer. ©2010 AACR.

  15. Vegetable-derived isothiocyanates: anti-proliferative activity and mechanism of action.

    Science.gov (United States)

    Zhang, Yuesheng; Yao, Song; Li, Jun

    2006-02-01

    Many isothiocyanates (ITC), which are available to human subjects mainly through consumption of cruciferous vegetables, demonstrate strong cancer-preventive activity in animal models. Human studies also show an inverse association between consumption of ITC and risk of cancer in several organs. Whereas earlier studies primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes and induce carcinogen-detoxifying enzymes, more recent investigations have shown that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular stress, which may be the initiating event for these effects. These findings shed new light on the mechanism of action of ITC and indicate that ITC may be useful both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated apoptosis, apparently resulting from mitochondrial damage, and also activate caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted; critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2 and Cdc25C, are down regulated or inhibited, and tubulin polymerization and spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates). Studies show that these dithiocarbamates are similar to their parent ITC in exerting anti-proliferative activity. Taken together, dietary ITC are highly-promising anti-cancer agents, capable of targetting multiple cellular components that are important for tumour cell survival and proliferation.

  16. A hemagglutinin from northeast red beans with immunomodulatory activity and anti-proliferative and apoptosis-inducing activities toward tumor cells.

    Science.gov (United States)

    Chan, Yau Sang; Wong, Jack Ho; Fang, Evandro Fei; Pan, Wenliang; Ng, Tzi Bun

    2013-10-01

    A 64-kDa hemagglutinin from a Phaseolus vulgaris cultivar, the northeast red bean, was purified by a protocol composed of three chromatographic steps involving affinity chromatography on Affi-gel blue gel, cation exchange chromatography on SP-Sepharose and FPLC-gel filtration on Superdex 75. The purified hemagglutinin appeared as a single 32-kDa band in SDS-PAGE indicating its dimeric nature. The N-terminal amino acid sequence of the hemagglutinin resembled the sequences of lectins and hemagglutinins from a number of Phaseolus species. The hemagglutinin manifested moderate thermostability and pH stability. It retained full activity up to 65 °C and in the pH range 2-12. It did not interact with simple sugars such as glucose, mannose and galactose. The hemagglutinin exerted immunostimulatory effects by upregulating the expression of cytokines like interferon-γ and tumor necrosis factor-α. It also exhibited antiproliferative activity on a number of tumor cells including MCF7 (breast cancer), HepG2 (liver cancer), CNE1 and CNE2 (nasopharyngeal cancer) cells, with stronger activity toward MCF7 and CNE1 cells. The hemagglutinin induced phophatidylserine externalization, mitochondrial depolarization and DNA condensation in MCF7 cells, indicating initiation of apoptosis. However, at high hemagglutinin concentrations, severe damage to the MCF7 cells was detected.

  17. Structural Basis of the Antiproliferative Activity of Largazole a Depsipeptide Inhibitor of the Histone Deacetylases

    Energy Technology Data Exchange (ETDEWEB)

    K Cole; D Dowling; M Boone; A Phillips; D Christianson

    2011-12-31

    Largazole is a macrocyclic depsipeptide originally isolated from the marine cyanobacterium Symploca sp., which is indigenous to the warm, blue-green waters of Key Largo, Florida (whence largazole derives its name). Largazole contains an unusual thiazoline-thiazole ring system that rigidifies its macrocyclic skeleton, and it also contains a lipophilic thioester side chain. Hydrolysis of the thioester in vivo yields largazole thiol, which exhibits remarkable antiproliferative effects and is believed to be the most potent inhibitor of the metal-dependent histone deacetylases (HDACs). Here, the 2.14 {angstrom}-resolution crystal structure of the HDAC8-largazole thiol complex is the first of an HDAC complexed with a macrocyclic inhibitor and reveals that ideal thiolate-zinc coordination geometry is the key chemical feature responsible for its exceptional affinity and biological activity. Notably, the core structure of largazole is conserved in romidepsin, a depsipeptide natural product formulated as the drug Istodax recently approved for cancer chemotherapy. Accordingly, the structure of the HDAC8-largazole thiol complex is the first to illustrate the mode of action of a new class of therapeutically important HDAC inhibitors.

  18. PDE5 Inhibitors-Loaded Nanovesicles: Physico-Chemical Properties and In Vitro Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Roberta F. De Rose

    2016-05-01

    Full Text Available Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP. Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase. Nanoliposomes, made up of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine monohydrate (DPPC, cholesterol, and N-(carbonyl-methoxypolyethylene glycol-2000-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-mPEG2000 (6:3:1 molar ratio, were characterized by a mean diameter of ~100 nm, a very low polydispersity index (~0.1 and a negative surface charge. The drugs did not influence the physico-chemical properties of the systems and were efficiently retained in the colloidal structure. By using cell count and MTT assay, we found a significant reduction of the viability in both cell lines following 24 h treatment with both nanoliposomal-encapsulated drugs, notably greater than the effect of the free drugs. Our findings demonstrate that nanoliposomes increase the antiproliferative activity of phosphodiesterase-5 inhibitors, providing a useful novel formulation for the treatment of thyroid carcinoma.

  19. A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics

    Science.gov (United States)

    Tan, Qunyou; Wu, Jianyong; Li, Yi; Mei, Hu; Zhao, Chunjing; Zhang, Jingqing

    2013-01-01

    The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca2+ accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.

  20. Assessment of antiproliferative and antiplasmodial activities of five selected Apocynaceae species

    Directory of Open Access Journals (Sweden)

    Abdullah Noor

    2011-01-01

    Full Text Available Abstract Background Studies have shown that the barks and roots of some Apocynaceae species have anticancer and antimalarial properties. In this study, leaf extracts of five selected species of Apocynaceae used in traditional medicine (Alstonia angustiloba, Calotropis gigantea, Dyera costulata, Kopsia fruticosa and Vallaris glabra were assessed for antiproliferative (APF and antiplasmodial (APM activities, and analysed for total alkaloid content (TAC, total phenolic content (TPC and radical-scavenging activity (RSA. As V. glabra leaf extracts showed wide spectrum APF and APM activities, they were further screened for saponins, tannins, cardenolides and terpenoids. Methods APF and APM activities were assessed using the sulphorhodamine B and lactate dehydrogenase assays, respectively. TAC, TPC and RSA were analysed using Dragendorff precipitation, Folin-Ciocalteu and DPPH assays, respectively. Screening for saponins, tannins, cardenolides and terpenoids were conducted using the frothing, ferric chloride, Kedde and vanillin-H2SO4 tests, respectively. Results Leaf extracts of A. angustiloba, C. gigantea and V. glabra displayed positive APF activity. Dichloromethane (DCM extract of C. gigantea, and DCM and DCM:MeOH extracts of V. glabra showed strong APF activity against all six human cancer cell lines tested. DCM extract of A. angustiloba was effective against three cancer cell lines. Against MCF-7 and MDA-MB-231 cell lines, DCM extract of C. gigantea was stronger than standard drugs of xanthorrhizol, curcumin and tamoxifen. All five species were effective against K1 strain of Plasmodium falciparum and three species (C. gigantea, D. costulata and K. fruticosa were effective against 3D7 strain. Against K1 strain, all four extracts of V. glabra displayed effective APM activity. Extracts of D. costulata were effective against 3D7 strain. Selectivity index values of extracts of A. angustiloba, C. gigantea and V. glabra suggested that they are

  1. Characterization and anti-proliferative activity of curcumin loaded chitosan nanoparticles in cervical cancer.

    Science.gov (United States)

    Khan, Md Asad; Zafaryab, Md; Mehdi, Syed Hassan; Ahmad, Irfan; Rizvi, M Moshahid A

    2016-12-01

    In the present study the chitosan nanoparticles (CsNPs) and curcumin loaded chitosan nanoparticles (CLCsNPs) were synthesized by tripolyphosphate (TPP) cross-linking method. The nanoparticles were prepared within a zone of appropriate chitosan and TPP concentrations. The average size of CsNPs and CLCsNPs were approximately 189±11.8nm and 197±16.8nm, exhibited a zeta potential of +76±5.6mV and +71±6.4mV respectively and drug entrapment efficiency was ≈85%. The CLCsNPs and CsNPs were further characterized by different physicochemical methods like transmission electron microscopy (TEM), dynamic light scattering (DLS), HPLC, MALDI-TOF, FT-IR, XRD and UV-vis Spectroscopy. In vitro studies revealed a fast release of ≈35% at pH 5 and ≈25% at pH 7.4 of the drug during the first 3h, followed by controlled release of curcumin over a period of 120h and sustained anti-proliferative activity of the drug in a dose and time dependent manner of CLCsNPs and combination with methyl jasmonate. The higher cytotoxicity effect of CLCsNPs may be due to their higher cellular uptake as compared to curcumin. Chitosan nanoparticles were not only stable but also a nontoxic. Our data suggested that curcumin loaded nanoformulations, therefore, might be promising candidates in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Potentiation of the antiproliferative activity of MKT-077 by loperamide, diltiazem and tamoxifen.

    Science.gov (United States)

    Abdul, Mansoor; Hoosein, Naseema

    2003-01-01

    MKT-077, a delocalized lipophilic cation, selectively targets cancer cells. MKT-077 has been reported to inhibit the growth of several tumor types and has undergone phase I clinical testing. We have examined the effect of MKT-077, alone and in combination with the antidiarrheal drug loperamide. Ten human cancer cell lines, four prostate (PC3, DU145, LNCaP, MDA-PCA-2B), two breast (MCF-7 and MDA-MB-231) and four colon (LoVo, Colo320DM, SW1116 and LS174t) were tested in vitro. Cells were grown to confluency prior to treatment. Loperamide potentiated the antiproliferative effect of MKT-077 in all ten cell lines, in a dose-dependent manner. The sensitivity of MDA-PCA-2B cells, the two breast and four colon cancer cell lines to MKT-077 was relatively low (>2.5 microg/ml MKT-077 required to inhibit growth by 95%). In these cell lines, 0.5-5 microg/ml (1-10 microM) loperamide caused a marked increase in the response to MKT-077. Loperamide is known to activate micro-opioid receptors at nanomolar concentrations and block voltage-gated calcium channels at micromolar doses. We found that calcium channel-blockers diltiazem and nifedipine (10-20 microg/ml), as well as tamoxifen (1.5-2.5 microg/ml) can also potentiate the growth-inhibitory effects of MKT-077. These synergistic interactions could be exploited for therapeutic benefit.

  3. The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells.

    Science.gov (United States)

    Palombo, John D; Ganguly, Aniruddha; Bistrian, Bruce R; Menard, Michael P

    2002-03-28

    The antiproliferative effects of two commercial preparations of conjugated linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA, c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT-29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium. The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer.

  4. Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex.

    Science.gov (United States)

    Jdir, Hamida; Khemakham, Bassem; Najjaa, Hanen; Chakroun, Mouna; Jridi, Mourad; Ben Arfa, Abdelkarim; Ben Ali, Yassine; Zouari, Nacim

    2016-10-01

    Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae). Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers. Materials and methods The anti-proliferative activity of the extracts (10-70 μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5-7.5 mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200 mg/kg) or indomethacin (50 mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods. Results Flower extracts contained a high level of polyphenolics (17.10-52.70 mg GAE/g) and flavonoids (74.20-100.60 mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC50 value: 12.50-27.10 μg/mL), DPPH(•) radical-scavenging (IC50 value: 0.20-0.40 mg/mL), Fe(3+ )reducing (EC50 value: 0.10-0.14 mg/mL) and Fe(2+ )chelating (IC50 value: 0.20-0.60 mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC50 value: 62.0-63.25 μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC50 value: 2.97 mg/mL) and reduced the paw oedema in mice (from 0.38 ± 0.01 to 0.24 ± 0.01 cm), 4 h post-carrageenan challenge. Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer.

  5. Antiproliferative, anti-aromatase, anti-17beta-HSD and antioxidant activities of lignans isolated from Myristica argentea.

    Science.gov (United States)

    Filleur, F; Le Bail, J C; Duroux, J L; Simon, A; Chulia, A J

    2001-11-01

    Four lignans were isolated from the petrol extract of Myristica argentea mace (Myristicaceae) and their structures were elucidated by means of NMR and mass spectrometry. Although they have been previously described, NMR data are only available for threo-austrobailignan-5, which has been isolated only once, and is incomplete. Three of them, erythro-austrobailignan-6, meso-dihydroguaiaretic acid and nectandrin-B, exert an antiproliferative effect on MCF-7 cells as well as antioxidant activity on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, but not the threo-austrobailignan-5. Nectandrin-B also possesses anti-17beta-hydroxysteroid dehydrogenase and anti-aromatase activities.

  6. 2-Anilino-4-(benzimidazol-2-yl)pyrimidines--a multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines.

    Science.gov (United States)

    Determann, Renate; Dreher, Jan; Baumann, Knut; Preu, Lutz; Jones, Peter G; Totzke, Frank; Schächtele, Christoph; Kubbutat, Michael H G; Kunick, Conrad

    2012-07-01

    2-Anilino-4-(benzimidazol-2-yl)-pyrimidines, synthesized by reaction of a readily available benzimidazole-substituted enaminone with suitable arylguanidines, were shown to inhibit four cancer-related protein kinases (Aurora B, PLK1, FAK, and VEGF-R2). The most potent derivative exhibited antiproliferative activity for several cancer cell lines of the NCI in vitro cell line panel in submicromolar concentrations. Both the anilinopyrimidine structure and the substitution pattern at the aniline ring appear to be important for the protein kinase inhibitory activity.

  7. Comparative antioxidant and antiproliferative activities of red and white pitayas and their correlation with flavonoid and polyphenol content.

    Science.gov (United States)

    Kim, HyoenJi; Choi, Hyung-Kyoon; Moon, Jeong Yong; Kim, Young Suk; Mosaddik, Ashik; Cho, Somi Kim

    2011-01-01

    Pitaya, commonly known as dragon fruit, has generated considerable consumer interest because of its attractive color and micronutrient content. The present study investigated the total polyphenol and flavonoid content, antioxidant activity against various free radicals, and antiproliferative effect on several cancer cell lines of extracts of flesh and peel of white and red pitayas, collected from Jeju Island, Korea. The total polyphenol and flavonoid contents of 80% methanol extracts of red pitaya peel (RPP) and white pitaya peel (WPP) were approximately 3- and 5-fold higher than those of red pitaya flesh (RPF) and white pitaya flesh (WPF), respectively. Overall, the total flavonoid and polyphenol contents of these extracts were RPP>WPP>RPF>WPF and WPP>RPP>RPF>WPF, respectively. In addition, a study involving nontargeted high-performance liquid chromatography coupled with a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA-ESI-MS) of different pitaya extracts indicated the presence of phenolic, hydroxycinnamic acid derivatives, flavonol glycosides, betacyanin, and its derivatives with a few unknown compounds. Separately, peel extracts of both red and white pitayas showed higher 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, and alkyl radical-scavenging activity than did the corresponding flesh extracts. Both peel extracts also showed stronger antiproliferative activity against AGS and MCF-7 cancer cells than either flesh extract. There was a direct correlation between the phenolic content and antioxidant effect, but no correlation observed between antioxidant activity and antiproliferative activity. These results suggest that the peel of white and red pitaya may be a valuable ingredient in foods and may also be useful in cosmetic, nutraceutical, and pharmaceutical applications.

  8. Synthesis and antiproliferative activity of benzophenone tagged pyridine analogues towards activation of caspase activated DNase mediated nuclear fragmentation in Dalton's lymphoma.

    Science.gov (United States)

    Al-Ghorbani, Mohammed; Thirusangu, Prabhu; Gurupadaswamy, H D; Girish, V; Shamanth Neralagundi, H G; Prabhakar, B T; Khanum, Shaukath Ara

    2016-04-01

    A series of benzophenones possessing pyridine nucleus 8a-l were synthesized by multistep reaction sequence and evaluated for antiproliferative activity against DLA cells by in vitro and in vivo studies. The results suggested that, compounds 8b with fluoro group and 8e with chloro substituent at the benzoyl ring of benzophenone scaffold as well as pyridine ring with hydroxy group exhibited significant activity. Further investigation in mouse model suggests that compounds 8b and 8e have the potency to activate caspase activated DNase (endonuclease) which is responsible for DNA fragmentation, a primary hallmark of apoptosis and thereby inhibits the Dalton's lymphoma ascites tumour growth.

  9. Antiproliferative activity in tumor cell lines, antioxidant capacity and total phenolic, flavonoid and tannin contents of Myrciaria floribunda

    Directory of Open Access Journals (Sweden)

    LUIS A.C. TIETBOHL

    Full Text Available ABSTRACT Myrciaria floribunda (H. West ex Willd. O. Berg, Myrtaceae, is a native plant species of the Atlantic Rain Forest, from north to south of Brazil. The lyophilized ethyl acetate extract from the leaves of M. floribunda was investigated for its antiproliferative activity in tumor cell lines, antioxidant capacity and its total phenolic, flavonoid and tannin contents. Antiproliferative activity was tested in vitro against seven human cancer cells and against immortalized human skin keratinocytes line (HaCat, no cancer cell. Antioxidant activity was determined using 1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging and oxygen radical absorbing capacity (ORAC assays and total phenolic, flavonoid and tannin contents were determined by spectrophotometric techniques. Ethyl acetate extract of M. floribunda exhibited antiproliferative activity against cancer cell lines with total growth inhibition (TGI between 69.70 and 172.10 µg/mL. For HaCat cell, TGI value was 213.60 µg/mL. M. floribunda showed a strong antioxidant potential: EC50 of 45.89±0.42 µg/mL and 0.55±0.05 mmol TE/g for DPPH and ORAC, respectively. Total phenolic content was 0.23±0.013g gallic acid equivalents (GAE/g extract and exhibited 13.10±1.60% of tannins content. The content of flavonoid was 24.08±0.44% expressed as rutin equivalents. These results provide a direction for further researches about the antitumoral potential of M. floribunda.

  10. In vitro and in vivo antiproliferative activity of Calotropis procera stem extracts

    Directory of Open Access Journals (Sweden)

    Hemerson I.F. Magalhães

    2010-06-01

    Full Text Available The cytotoxic potential of stem organic extracts from Calotropis procera (Asclepiadaceae was firstly evaluated against cancer cell lines by MTT assay. Subsequently, samples considered cytotoxic were tested for antimitotic activity on sea urchin egg development and for in vivo antiproliferative activity in mice bearing Sarcoma 180 tumor. Among the five extracts (hexane, dichloromethane, ethyl acetate, acetone and methanol, ethyl acetate and acetone extracts displayed higher cytotoxic potential against tumor cells, with IC50 ranging from 0.8 to 4.4 μg/mL, while methanolic extract was weakly cytotoxic. Cytotoxic extracts also exhibited cell division inhibition capacity by antimitotic assay, revealing IC50 values lower than 5 μg/mL. In the in vivo antitumor assessments, ethyl acetate- and acetone-treated animals showed tumor growth inhibition ratios of 64.3 and 53.1%, respectively, with reversible toxic effects on liver and kidneys. Further studies are in progress in order to identify C. procera cytotoxic compound(s and to understand the mechanism of action responsible for this tumor-decreasing potential.O potencial citotóxico de extratos orgânicos do caule de Calotropis procera (Asclepiadaceae foi primeiramente avaliado frente a linhagens de células tumorais através do ensaio de MTT. Aquelas amostras consideradas citotóxicas foram sub-sequentemente testadas para atividade antimitótica sobre o desenvolvimento de ovos de ouriço-do-mar e para atividade antiproliferativa in vivo em camundongos transplantados com tumor Sarcoma 180. Dentre os cinco extratos estudados (hexano, diclorometano, acetato de etila, acetona e metanol, os extratos acetato de etila e acetona mostraram maior potencial citotóxico contra células tumorais, com CI50 variando de 0,8 to 4,4 μg/mL, enquanto o extrato metanólico revelou ser fracamente citotóxico. s extratos citotóxicos também exibiram capacidade de inibição da divisão celular com valores de CI50 menores

  11. ASSOCIATION BETWEEN ANTI-PROLIFERATIVE ACTIVITY OF EVERNIA PRUNASTRI WITH THE CELLULAR APOPTOTIC PATHWAYS

    OpenAIRE

    YUMRUTAŞ, Önder; Güven, Celal; Ozay, Yusuf; Albeniz, Işıl; ahbap, Mufide Aydogan; Bozgeyik, Ibrahim; Yıldız, Atilla; Bagıs, Haydar; Sener, Leyla Turker

    2017-01-01

    Lichens have been used for medical purposes formany years. Evernia prunastri (L.)Ach, belonging to Parmeliaceae, is an important lichen species in Turkey.Previous studies was reported that E.prunastri have significant antioxidant, antimicrobial and anticancercompounds in its structure. Although the antiproliferative effects of E. prunastri are determined in sometypes of cancer, there is little information about the pathway of thisactivity. Accordingly, we aimed to determine the association be...

  12. Evaluation of the antiproliferative activity of the leaves from Arctium lappa by a bioassay-guided fractionation.

    Science.gov (United States)

    Machado, Fabio Bahls; Yamamoto, Rafael Eidi; Zanoli, Karine; Nocchi, Samara Requena; Novello, Cláudio Roberto; Schuquel, Ivânia Teresinha Albrecht; Sakuragui, Cássia Mônica; Luftmann, Heinrich; Ueda-Nakamura, Tânia; Nakamura, Celso Vataru; de Mello, João Carlos Palazzo

    2012-02-14

    Arctium lappa L. (Asteraceae) is used in folk medicine around the World, and shows several kinds of biological activity, particularly in vitro antitumor activity in different cell lines. This study evaluated the antiproliferative activity of the crude extract, semipurified fractions, and isolated compounds from the leaves of A. lappa, through bioassay-guided testing in Caco-2 cells. The crude extract was obtained with a 50% hydroethanolic extract and then partitioned with hexane, ethyl acetate, and n-butanol. The ethyl-acetate fraction (EAF) showed antiproliferative activity. This fraction was subjected to sequential column chromatography over silica gel to afford onopordopicrin (1), mixtures of 1 with dehydromelitensin-8-(4'-hydroxymethacrylate) (2), a mixture of 2 with dehydromelitensin (3), mixture of 1 with melitensin (4), dehydrovomifoliol (5), and loliolide (6). The compounds were identified by spectroscopic methods (NMR, MS) and comparison with literature data. This is the first description of compounds 2-5 from this species. The compounds tested in Caco-2 cells showed the following CC(50) (µg/mL) values: 1: 19.7 ± 3.4, 1 with 2: 24.6 ± 1.5, 2 with 3: 27 ± 11.7, 1 with 4: 42 ± 13.1, 6 30 ± 6.2; compound 5 showed no activity.

  13. Evaluation of the Antiproliferative Activity of the Leaves from Arctium lappa by a Bioassay-Guided Fractionation

    Directory of Open Access Journals (Sweden)

    Celso Vataru Nakamura

    2012-02-01

    Full Text Available Arctium lappa L. (Asteraceae is used in folk medicine around the World, and shows several kinds of biological activity, particularly in vitro antitumor activity in different cell lines. This study evaluated the antiproliferative activity of the crude extract, semipurified fractions, and isolated compounds from the leaves of A. lappa, through bioassay-guided testing in Caco-2 cells. The crude extract was obtained with a 50% hydroethanolic extract and then partitioned with hexane, ethyl acetate, and n-butanol. The ethyl-acetate fraction (EAF showed antiproliferative activity. This fraction was subjected to sequential column chromatography over silica gel to afford onopordopicrin (1, mixtures of 1 with dehydromelitensin-8-(4'-hydroxymethacrylate (2, a mixture of 2 with dehydromelitensin (3, mixture of 1 with melitensin (4, dehydrovomifoliol (5, and loliolide (6. The compounds were identified by spectroscopic methods (NMR, MS and comparison with literature data. This is the first description of compounds 2–5 from this species. The compounds tested in Caco-2 cells showed the following CC50 (µg/mL values: 1: 19.7 ± 3.4, 1 with 2: 24.6 ± 1.5, 2 with 3: 27 ± 11.7, 1 with 4: 42 ± 13.1, 6 30 ± 6.2; compound 5 showed no activity.

  14. Synthesis and antiproliferative activity of the ring system [1,2]oxazolo[4,5-g]indole.

    Science.gov (United States)

    Barraja, Paola; Caracausi, Libero; Diana, Patrizia; Spanò, Virginia; Montalbano, Alessandra; Carbone, Anna; Parrino, Barbara; Cirrincione, Girolamo

    2012-11-01

    Brand new ring: A series of 27 derivatives of the new ring system [1,2]oxazolo[4,5-g]indole were conveniently prepared and tested at the NCI for antiproliferative studies. Several of them showed good inhibitory activity toward all tested cell lines, reaching GI50 values generally at the micromolar and sub-micromolar levels and in some cases at nanomolar concentrations. The mean GI50 values, calculated on the full panel, were in the range 0.25-7.08 μM.

  15. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tao; Meng, Lingjun [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States); Tsai, Robert Y.L., E-mail: rtsai@ibt.tamhsc.edu [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States)

    2011-10-22

    Highlights: {yields} Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. {yields} Cell type-dependent synergy between MPA and anti-proliferative agents. {yields} The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. {yields} The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  16. Determination of the Antiproliferative Activity of New Theobromine Derivatives and Evaluation of Their In Vitro Hepatotoxic Effects.

    Science.gov (United States)

    Georgieva, Maya; Kondeva-Burdina, Magdalena; Mitkov, Javor; Tzankova, Virginia; Momekov, Georgi; Zlatkov, Alexander

    2016-01-01

    A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized. Their anti-proliferative activity against human chronic myelocytic leukemia cell K562, human T-cell leukemia cell SKW-3 and human acute myeloid leukemia HL-60 was evaluated. For the tested compounds a concentrationdependent cytotoxic activity was observed, with 7g outlined as the most active compound within the series. The targed compounds were obtained in yields of 56 to 85% and their structures were elucidated by FTIR, (1)H NMR, (13)C NMR and microanalyses. The compounds purity was proven by elemental analysis and spectral data. In general, the compounds showed low hepatotoxicity on sub-cellular and cellular level. On isolated rat microsomes only 7d showed toxic effect while theobromine, 1-benzyl-theobromine-thioacetic acid (BTTA) and the other new theobromine derivatives were devoid of toxicity. In isolated rat hepatocytes, when compared to theobromine and BTTA, 7f showed lower cytotoxic effects, and 7d exerted higher cytotoxicity. The results indicate 7g as a promising structure for the design of future compounds with low hepatotoxicity and good antiproliferative activity.

  17. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells.

    Science.gov (United States)

    Liao, Wenzhen; Chen, Luying; Ma, Xiang; Jiao, Rui; Li, Xiaofeng; Wang, Yong

    2016-05-23

    The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction.

  18. Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest.

    Directory of Open Access Journals (Sweden)

    Md Sultan Ahamad

    Full Text Available A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p<0.01 with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed statistically significant (p<0.001 dose-related increment in ROS production for naringenin. It also caused naringenin-mediated epidermoid carcinoma apoptosis by inducing mitochondrial depolarization. Cell cycle study showed that naringenin induced cell cycle arrest in G0/G1 phase of cell cycle and caspase-3 analysis revealed a dose dependent increment in caspase-3 activity which led to cell apoptosis. This study confirms the efficacy of naringenin that lead to cell death in epidermoid carcinoma cells via inducing ROS generation, mitochondrial depolarization, nuclear condensation, DNA fragmentation, cell cycle arrest in G0/G1 phase and caspase-3 activation.

  19. Potential antimicrobial and antiproliferative activities of autochthonous starter cultures and protease EPg222 in dry-fermented sausages.

    Science.gov (United States)

    Fernández, Margarita; Ruiz-Moyano, Santiago; Benito, María José; Martín, Alberto; Hernández, Alejandro; Córdoba, María de Guía

    2016-05-18

    This work studied the presence of nitrogen compounds with bioactive properties in Iberian pork sausages that were manufactured using different autochthonous starter cultures (Pediococcus acidilactici MS200 and Staphylococcus vitulus RS34) and protease EPg222. Nitrogen compounds were extracted and evaluated for their antimicrobial effect against spoilage and pathogenic bacteria, such as Bacillus cereus, Escherichia coli, Salmonella choleraesuis, Staphylococcus aureus and Listeria monocytogenes, and antiproliferative activity on the HT-29 colon adenocarcinoma cell line. Dry-fermented sausages elaborated with starter cultures P200S34 and protease EPg222 generate extracts that cause inhibition of the growth of pathogens reaching 25% inhibition of Bacillus cereus, making this a promising tool for biocontrol in the meat industry. On the other hand, the inoculation of well-adapted starter cultures with high proteolytic activity also increased the antiproliferative activity of these extracts, around 45% inhibition at 72 h, mainly due to an increase in free amino acids, such as Lys and Pro, but also small peptides.

  20. Antiproliferative Activity and in Vivo Toxicity of Double-Point Modified Analogs of 1,25-Dihydroxyergocalciferol.

    Science.gov (United States)

    Trynda, Justyna; Turlej, Eliza; Milczarek, Magdalena; Pietraszek, Anita; Chodyński, Michał; Kutner, Andrzej; Wietrzyk, Joanna

    2015-10-20

    Analogs of 1,25-dihydroxyergocalciferol, modified in the side-chain and in the A-ring, were tested for their antiproliferative activity against a series of human cancer cell lines in vitro and in vivo toxicity. The proliferation inhibition caused by the analogs was higher than that of the parent compounds, while the toxicity, measured as the serum calcium level, was lower. All analogs were able to induce, in HL-60 and MV4-11 leukemic cells, G₀/G₁ cell cycle arrest and differentiation expressed as morphological signs typical for monocytes. The analogs also induced the expression of CD11b and/or CD14 cell-differentiation markers. The most potent analogs, PRI-5105, PRI-5106, PRI-5201 and PRI-5202, were also able to induce vitamin D receptor (VDR) protein expression, mainly in the cytoplasmic fraction of HL-60 or MV4-11 cells. The most active analogs were the 19-nor ones with an extended and rigidified side-chain (PRI-5201 and PRI-5202), as in the former analogs PRI-1906 and PRI-1907. Epimerization at C-24 (PRI-5101) or introduction of an additional hydroxyl at C-23 (PRI-5104) reduced the toxicity of the analog with retained antiproliferative activity.

  1. Antiproliferative Activity and in Vivo Toxicity of Double-Point Modified Analogs of 1,25-Dihydroxyergocalciferol

    Directory of Open Access Journals (Sweden)

    Justyna Trynda

    2015-10-01

    Full Text Available Analogs of 1,25-dihydroxyergocalciferol, modified in the side-chain and in the A-ring, were tested for their antiproliferative activity against a series of human cancer cell lines in vitro and in vivo toxicity. The proliferation inhibition caused by the analogs was higher than that of the parent compounds, while the toxicity, measured as the serum calcium level, was lower. All analogs were able to induce, in HL-60 and MV4-11 leukemic cells, G0/G1 cell cycle arrest and differentiation expressed as morphological signs typical for monocytes. The analogs also induced the expression of CD11b and/or CD14 cell-differentiation markers. The most potent analogs, PRI-5105, PRI-5106, PRI-5201 and PRI-5202, were also able to induce vitamin D receptor (VDR protein expression, mainly in the cytoplasmic fraction of HL-60 or MV4-11 cells. The most active analogs were the 19-nor ones with an extended and rigidified side-chain (PRI-5201 and PRI-5202, as in the former analogs PRI-1906 and PRI-1907. Epimerization at C-24 (PRI-5101 or introduction of an additional hydroxyl at C-23 (PRI-5104 reduced the toxicity of the analog with retained antiproliferative activity.

  2. Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and their in vitro antiproliferative activity.

    Science.gov (United States)

    Pandey, Renu; Mahar, Rohit; Hasanain, Mohammad; Shukla, Sanjeev K; Sarkar, Jayanta; Rameshkumar, K B; Kumar, Brijesh

    2016-11-15

    Efficient and sensitive LC-MS/MS methods have been developed for the rapid screening and determination of bioactive compounds in different fruit parts of four Myristica species, viz., Myristica beddomeii, Myristica fragrans, Myristica fatua and Myristica malabarica. Twenty-one compounds were identified and characterized on the basis of their accurate mass and MS/MS fragmentation pattern using HPLC-QTOF-MS/MS and NMR analysis. Quantitative determination of five major bioactive compounds was performed using multiple-reaction monitoring mode with continuous polarity switching by UHPLC-QqQLIT-MS/MS. Moreover, in vitro antiproliferative activity of these Myristica species was evaluated against five human cancer cell lines A549, DLD-1, DU145, FaDu and MCF-7 using SRB assay. Seventeen phytoconstituents were identified and reported for the first time from M. beddomeii and sixteen from M. fatua. Quantification result showed highest total content of five major bioactive compounds in mace of M. fragrans. Evaluation of in vitro antiproliferative activity revealed potent activity in all investigated species except M. fragrans.

  3. Evaluation of different extraction methods from pomegranate whole fruit or peels and the antioxidant and antiproliferative activity of the polyphenolic fraction.

    Science.gov (United States)

    Masci, Alessandra; Coccia, Andrea; Lendaro, Eugenio; Mosca, Luciana; Paolicelli, Patrizia; Cesa, Stefania

    2016-07-01

    Pomegranate is a functional food of great interest, due to its multiple beneficial effects on human health. This fruit is rich in anthocyanins and ellagitannins, which exert a protective role towards degenerative diseases. The aim of the present work was to optimize the extraction procedure, from different parts of the fruit, to obtain extracts enriched in selected polyphenols while retaining biological activity. Whole fruits or peels of pomegranate cultivars, with different geographic origin, were subjected to several extraction methods. The obtained extracts were analyzed for polyphenolic content, evaluated for antioxidant capacity and tested for antiproliferative activity on human bladder cancer T24 cells. Two different extraction procedures, employing ethyl acetate as a solvent, were useful in obtaining extracts enriched in ellagic acid and/or punicalagins. Antioxidative and antiproliferative assays demonstrated that the antioxidant capability is directly related to the phenolic content, whereas the antiproliferative activity is to be mainly attributed to ellagic acid.

  4. Evaluation of the Volatile Oil Composition and Antiproliferative Activity of Laurus nobilis L. (Lauraceae on Breast Cancer Cell Line Models

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    Rana Abu-Dahab

    2014-03-01

    Full Text Available Volatile oil composition and antiproliferative activity of Laurus nobilis L. (Lauraceae fruits and leaves grown in Jordan were investigated. GC-MS analysis of the essential oil of the fruits resulted in the identification of 45 components representing 99.7 % of the total oil content, while the leaf essential oil yielded 37 compounds representing 93.7% of the total oil content. Oxygenated monoterpene 1,8-cineole was the main component in the fruit and leaf oils. Using sulphorhodamine B assay; the crude ethanol fraction, among other solvent extracts, showed strong antiproliferative activity for both leaves and fruits, nevertheless, the fruits were more potent against both breast cancer cell models (MCF7 and T47D. At IC 50 values ; the mechanism of apoptosis was nevertheless different: where L. nobilis fruit proapoptotic efficacy was not regulated by either p53 or p21, L. nobilis leaf extract components enhanced the p53 levels substantially. In both extracts, apoptosis was not caspase-8 or Fas Ligand and sFas (Fas/APO-1 dependent. Our studies highlight L. nobilis as a potential natural agent for breast cancer therapy. Compared with non induced basal cells, both L. nobilis fruits and leaves induced a significant enrichment in the cytoplasmic mono- and oligonucleosomes after assumed induction of programmed MCF7 cell death.

  5. Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells.

    Science.gov (United States)

    Pilarski, Radosław; Poczekaj-Kostrzewska, Magdalena; Ciesiołka, Danuta; Szyfter, Krzysztof; Gulewicz, Krzysztof

    2007-01-01

    The woody Amazonian vine Uncaria tomentosa (cat's claw) has been recently more and more popular all over the world as an immunomodulatory, antiinflammatory and anti-cancer remedy. This study investigates anti-proliferative potency of several cat's claw preparations with different quantitative and qualitative alkaloid contents on HL-60 acute promyelocytic human cells by applying trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay (MTT). By standardization and statistical comparison of the obtained results pteropodine and isomitraphylline are indicated to be most suitable for standardization of medical cat's claw preparations.

  6. Novel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity

    Science.gov (United States)

    Kale, Sangram S.; Jedhe, Ganesh S.; Meshram, Sachin N.; Santra, Manas K.; Hamel, Ernest; Sanjayan, Gangadhar J.

    2015-01-01

    We describe the design, synthesis and SAR profiling of a series of novel combretastatin–nocodazole conjugates as potential anticancer agents. The thiophene ring in the nocodazole moiety was replaced by a substituted phenyl ring from the combretastatin moiety to design novel hybrid analogues. The hydroxyl group at the ortho position in compounds 2, 3 and 4 was used as the conformationally locking tool by anticipated six-membered hydrogen bonding. The bioactivity profiles of all compounds as tubulin polymerization inhibitors and as antiproliferative agents against the A-549 human lung cancer cell line were investigated Compounds 1 and 4 showed μM IC50 values in both assays. PMID:25817588

  7. Synthesis of Aromatic Retinoids and Curcuminoids and Evaluation of their Antiproliferative, Antiradical, and Anti‐inflammatory Activities

    Science.gov (United States)

    Morzycki, Jacek W.; Rárová, Lucie; Grúz, Jiři; Sawczuk, Tomasz; Kiełczewska, Urszula; Siergiejczyk, Leszek

    2016-01-01

    Abstract Natural retinoids and curcuminoids are known for their broad spectrum of biological properties, such as antioxidant, anti‐inflammatory, antitumor, and so forth. In this work, a convenient synthesis of aromatic retinoids and curcuminoids from vinyl or allyl ketones, and the corresponding alcohols, using olefin metathesis as a key reaction, was elaborated. The best yields and diastereoselectivities were obtained from allylic or homoallylic alcohols by employing the two‐step cross‐metathesis/oxidation procedure. The synthesized analogues were tested for their antiproliferative activity on human cancer cell lines of various origin (leukemia CEM, adenocarcinoma MCF7, cervical carcinoma HeLa) as well as for their antioxidant and anti‐inflammatory activity in vitro. All examined derivatives exhibited strong anti‐inflammatory activity in vitro without affecting cell viability. They also showed strong cytotoxicity against leukemia cell line CEM, except for 18 and 35. The antioxidant activity of the tested compounds was rather weak. PMID:27547644

  8. Striking difference in antiproliferative activity of ruthenium- and osmium-nitrosyl complexes with azole heterocycles.

    Science.gov (United States)

    Büchel, Gabriel E; Gavriluta, Anatolie; Novak, Maria; Meier, Samuel M; Jakupec, Michael A; Cuzan, Olesea; Turta, Constantin; Tommasino, Jean-Bernard; Jeanneau, Erwann; Novitchi, Ghenadie; Luneau, Dominique; Arion, Vladimir B

    2013-06-03

    Ruthenium nitrosyl complexes of the general formulas (cation)(+)[cis-RuCl4(NO)(Hazole)](-), where (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (Hind) (1c), (cation)(+) = (H2pz)(+), Hazole = 1H-pyrazole (Hpz) (2c), (cation)(+) = (H2bzim)(+), Hazole = 1H-benzimidazole (Hbzim) (3c), (cation)(+) = (H2im)(+), Hazole = 1H-imidazole (Him) (4c) and (cation)(+)[trans-RuCl4(NO)(Hazole)](-), where (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (1t), (cation)(+) = (H2pz)(+), Hazole = 1H-pyrazole (2t), as well as osmium analogues of the general formulas (cation)(+)[cis-OsCl4(NO)(Hazole)](-), where (cation)(+) = (n-Bu4N)(+), Hazole =1H-indazole (5c), 1H-pyrazole (6c), 1H-benzimidazole (7c), 1H-imidazole (8c), (cation)(+) = Na(+); Hazole =1H-indazole (9c), 1H-benzimidazole (10c), (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (11c), (cation)(+) = H2pz(+), Hazole = 1H-pyrazole (12c), (cation)(+) = (H2im)(+), Hazole = 1H-imidazole (13c), and (cation)(+)[trans-OsCl4(NO)(Hazole)](-), where (cation)(+) = n-Bu4N(+), Hazole = 1H-indazole (5t), 1H-pyrazole (6t), (cation)(+) = Na(+), Hazole = 1H-indazole (9t), (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (11t), (cation)(+) = (H2pz)(+), Hazole = 1H-pyrazole (12t), have been synthesized. The compounds have been comprehensively characterized by elemental analysis, ESI mass spectrometry, spectroscopic techniques (IR, UV-vis, 1D and 2D NMR) and X-ray crystallography (1c·CHCl3, 1t·CHCl3, 2t, 3c, 6c, 6t, 8c). The antiproliferative activity of water-soluble compounds (1c, 1t, 3c, 4c and 9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c) in the human cancer cell lines A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma) has been assayed. The effects of metal (Ru vs Os), cis/trans isomerism, and azole heterocycle identity on cytotoxic potency and cell line selectivity have been elucidated. Ruthenium complexes (1c, 1t, 3c, and 4c) yielded IC50 values in the low micromolar concentration range. In contrast to most

  9. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    Directory of Open Access Journals (Sweden)

    Bagora Bayala

    Full Text Available This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78% and β-caryophyllene (10.54% for Ocimum basilicum; 1, 8-cineol (31.22%, camphor (12.730%, α-pinene (6.87% and trans α-bergamotene (5.32% for Ocimum americanum; β-caryophyllene (21%, α-pinene (20.11%, sabinene (10.26%, β-pinene (9.22% and α-phellandrene (7.03% for Hyptis spicigera; p-cymene (25.27%, β-caryophyllene (12.70%, thymol (11.88, γ-terpinene (9.17% and thymyle acetate (7.64% for Lippia multiflora; precocene (82.10%for Ageratum conyzoides; eucalyptol (59.55%, α-pinene (9.17% and limonene (8.76% for Eucalyptus camaldulensis; arcurcumene (16.67%, camphene (12.70%, zingiberene (8.40%, β-bisabolene (7.83% and β-sesquiphellandrène (5.34% for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides showed the

  10. Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

    Science.gov (United States)

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  11. Chemical Composition, Antioxidant, Anti-Inflammatory and Anti-Proliferative Activities of Essential Oils of Plants from Burkina Faso

    Science.gov (United States)

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A.; Simpore, Jacques

    2014-01-01

    This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography–mass spectrometry and gas chromatography–flame ionization detector. Major constituents were α-terpineol (59.78%) and β-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; β-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), β-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), β-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), β-bisabolene (7.83%) and β-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides

  12. The flavonoid content and antiproliferative, hypoglycaemic, anti-inflammatory and free radical scavenging activities of Annona dioica St. Hill

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    Formagio Anelise S N

    2013-01-01

    Full Text Available Abstract Background Annona dioica St. Hill (Annonacaeae is a Brazilian plant used in folk medicine for the treatment of several types of rheumatisms and diarrhoea. The focus of this work was to evaluate the in vitro antiproliferative and antioxidant activity and the in vivo hypoglycaemic and anti-inflammatory activity of A. dioica and identify the principal constituents of this plant. Methods The crude methanol extract (EAD and hexane (HF, chloroform (CF, ethyl acetate (EAF and hydromethanol fractions (HMF were evaluated for free radical scavenging activity using the DPPH assay. The EAD and EAF were assayed for hypoglycaemic activity in rats. The EAD was tested in an antiproliferation assay and for anti-inflammatory effects in paw oedema, in addition to myeloperoxidase activity induced by carrageenan (Cg in mice. The EAF was assayed using chromatographic methods. Results The fractionation of the EAF through chromatographic methods identified derivatives of the flavonoids quercetin and kaempferol. Among all the tested fractions, the ethyl acetate and hydromethanol fractions were the most potent, exhibiting an IC50 of 8.53 and 10.57 μg/mL, respectively, which is comparable to that of the commercial antioxidant butylated hydroxytoluene (BHT. The oral administration of the EAD (100 mg/kg and EAF (15 mg/kg inhibited the increase of glucose levels, resulting in a hypoglycaemic effect. The EAD (30 to 300 mg/kg exhibited an anti-oedematogenic effect in Cg-induced paw oedema in a time- and dose-dependent manner. The results showed a reduction of MPO activity by A. dioica 6 h after the induction of paw oedema at all doses tested with maximal inhibition at 300 mg/kg. Conclusions Our results reveal for the first time that compounds contained in the A. dioica leaves exert anti-inflammatory, hypoglycaemic, antiproliferative, and antioxidant effects. The antioxidant activity may be associated with the presence of flavonoids.

  13. Assessment of white grape pomace from winemaking as source of bioactive compounds, and its antiproliferative activity.

    Science.gov (United States)

    Jara-Palacios, M José; Hernanz, Dolores; Cifuentes-Gomez, Tania; Escudero-Gilete, M Luisa; Heredia, Francisco J; Spencer, Jeremy P E

    2015-09-15

    The antiproliferative effects of a purified white grape pomace extract (PWGPE), as well as of some phenolic standards on colon cancer cells were examined. The phenolic composition of the PWGPE was determined by rapid resolution liquid chromatography/mass spectrometry (RRLC/MS). The PWGPE had 92.6, 43.3 and 6.01mg/g of flavanols, flavonols and phenolic acids, respectively and, along with pure catechin, epicatechin, quercetin and gallic acid, they were all found capable of inhibiting cellular proliferation. PWGPE (100μg/ml) inhibited the proliferation of cells by 52.1% at 48h, whilst catechin, epicatechin, quercetin and gallic acid (60μg/ml) inhibited growth by 65.2%, 62.2%, 81.0% and 71.0%, respectively, at 72h. The PWGPE is an interesting source of phenolic compounds with antiproliferative properties, that could be of interest in the food and pharmaceutical industries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides.

    Science.gov (United States)

    Quintana-Espinoza, Patricia; García-Luis, Jonay; Amesty, Angel; Martín-Rodríguez, Patricia; Lorenzo-Castrillejo, Isabel; Ravelo, Angel G; Fernández-Pérez, Leandro; Machín, Félix; Estévez-Braun, Ana

    2013-11-01

    A series of arylnaphthalimides were designed and synthesized to overcome the dose-limiting cytotoxicity of N-acetylated metabolites arising from amonafide, the prototypical antitumour naphthalimide whose biomedical properties have been related to its ability to intercalate the DNA and poison the enzyme Topoisomerase II. Thus, these arylnaphthalimides were first evaluated for their antiproliferative activity against two tumour cell lines and for their antitopoisomerase II in vitro activities, together with their ability to intercalate the DNA in vitro and also through docking modelization. Then, the well-known DNA damage response in Saccharomyces cerevisiae was employed to critically evaluate whether these novel compounds can damage the DNA in vivo. By performing all these assays we conclude that the 5-arylsubstituted naphthalimides not only keep but also improve amonafide's biological activities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents.

    Science.gov (United States)

    Lobb, Karen L; Hipskind, Philip A; Aikins, James A; Alvarez, Enrique; Cheung, Yiu-Yin; Considine, Eileen L; De Dios, Alfonso; Durst, Gregory L; Ferritto, Rafael; Grossman, Cora Sue; Giera, Deborah D; Hollister, Beth A; Huang, Zhongping; Iversen, Philip W; Law, Kevin L; Li, Tiechao; Lin, Ho-Shen; Lopez, Beatriz; Lopez, Jose E; Cabrejas, Luisa M Martin; McCann, Denis J; Molero, Victoriano; Reilly, John E; Richett, Michael E; Shih, Chuan; Teicher, Beverly; Wikel, James H; White, Wesley T; Mader, Mary M

    2004-10-21

    Two closely related diaryl acylsulfonamides were recently reported as potent antitumor agents against a broad spectrum of human tumor xenografts (colon, lung, breast, ovary, and prostate) in nude mice. Especially intriguing was their activity against colorectal cancer xenografts. In this paper, rapid parallel synthesis along with traditional medicinal chemistry techniques were used to quickly delineate the structure-activity relationships of the substitution patterns in both phenyl rings of the acylsufonamide anti-proliferative scaffold. Although the molecular target of the compounds remains unclear, we determined that the vascular endothelial growth factor-dependent human umbilical vein endothelial cells assay in combination with a soft agar disk diffusion assay allowed for optimization of potency in the series. The pharmacokinetic properties and in vivo activity in an HCT116 xenograft model are reported for representative compounds.

  16. Molecular association of 2-(n-alkylamino)-1,4-naphthoquinone derivatives: Electrochemical, DFT studies and antiproliferative activity against leukemia cell lines

    Science.gov (United States)

    Patil, Rishikesh; Bhand, Sujit; Konkimalla, V. Badireenath; Banerjee, Priyabrata; Ugale, Bharat; Chadar, Dattatray; Saha, Sourav Kr.; Praharaj, Prakash Priyadarshi; Nagaraja, C. M.; Chakrovarty, Debamitra; Salunke-Gawali, Sunita

    2016-12-01

    Molecular structures and their molecular association of 2-(n-alkylamino)-1,4-naphthoquinone, viz., LH-3; propyl, LH-4; butyl and LH-8; octyl derivatives were studied by single crystal X-ray diffraction studies. Synthesis and characterization of 2-octylamino-1,4-naphthoquinone; LH-8 was discussed. The molecule of LH-3 crystallizes in orthorhombic space group P21/c, while the LH-4 and LH-8 molecule crystallizes in triclinic space group P-1. LH-3, LH-4 and LH-8 showed intermolecular N-H⋯O and C-H⋯O interactions, LH-3 showed unique C(3)-H(3)⋯O(1) interaction. Interchain π-π stacking, slipped π-π stacking and C⋯O close contacts was respectively observed in LH-3, LH-4 and LH-8. Electrochemical studies were performed on first eight members of homologous series of 2-(n-alkylamino)-1,4-naphthoquinone (LH-1 to LH-8) by cyclic voltammetry. Naphthoquinone to naphthosemiquinone reversible redox couple was observed in all compounds ∼ E1/2 = -0.657 ± 0.05 V. HOMO-LUMO band gap was determined for the neutral form as well as the monoanionic radical form viz. naphthosemiquinone form of selected derivatives by DFT studies. It has been observed that the electron density is delocalized in the naphthoquinone ring in both neutral as well as one electron reduced form of compounds. Antiproliferative activity of LH-1 to LH-8 was evaluated against two cancer cell lines, THP1(acute monocytic leukemia) and K562(human immortalized myelogenous leukemia cell line) cells. It was observed that, in THP1 cells, compounds LH-2 and LH-3 are very active while LH-1, LH-4 and LH-6 were moderately active and LH-5, LH-7 and LH-8 were totally inactive. Contrastingly, in K562 cells all of the compounds were moderately active.

  17. Isolation of a glucosamine binding leguminous lectin with mitogenic activity towards splenocytes and anti-proliferative activity towards tumor cells.

    Directory of Open Access Journals (Sweden)

    Yau Sang Chan

    Full Text Available A dimeric 64-kDa glucosamine-specific lectin was purified from seeds of Phaseolus vulgaris cv. "brown kidney bean." The simple 2-step purification protocol involved affinity chromatography on Affi-gel blue gel and gel filtration by FPLC on Superdex 75. The lectin was absorbed on Affi-gel blue gel and desorbed using 1M NaCl in the starting buffer. Gel filtration on Superdex 75 yielded a major absorbance peak that gave a single 32-kDa band in SDS-PAGE. Hemagglutinating activity was completely preserved when the ambient temperature was in the range of 20 °C-60 °C. However, drastic reduction of the activity occurred at temperatures above 65 °C. Full hemagglutinating activity of the lectin was observed at an ambient pH of 3 to 12. About 50% activity remained at pH 0-2, and only residual activity was observed at pH 13-14. Hemagglutinating activity of the lectin was inhibited by glucosamine. The brown kidney bean lectin elicited maximum mitogenic activity toward murine splenocytes at 2.5 µM. The mitogenic activity was nearly completely eliminated in the presence of 250 mM glucosamine. The lectin also increased mRNA expression of the cytokines IL-2, TNF-α and IFN-γ. The lectin exhibited antiproliferative activity toward human breast cancer (MCF7 cells, hepatoma (HepG2 cells and nasopharyngeal carcinoma (CNE1 and CNE2 cells with IC(50 of 5.12 µM, 32.85 µM, 3.12 µM and 40.12 µM respectively after treatment for 24 hours. Flow cytometry with Annexin V and propidum iodide staining indicated apoptosis of MCF7 cells. Hoechst 33342 staining also indicated formation of apoptotic bodies in MCF7 cells after exposure to brown kidney bean lectin. Western blotting revealed that the lectin-induced apoptosis involved ER stress and unfolded protein response.

  18. Isolation of a glucosamine binding leguminous lectin with mitogenic activity towards splenocytes and anti-proliferative activity towards tumor cells.

    Science.gov (United States)

    Chan, Yau Sang; Wong, Jack Ho; Fang, Evandro Fei; Pan, Wenliang; Ng, Tzi Bun

    2012-01-01

    A dimeric 64-kDa glucosamine-specific lectin was purified from seeds of Phaseolus vulgaris cv. "brown kidney bean." The simple 2-step purification protocol involved affinity chromatography on Affi-gel blue gel and gel filtration by FPLC on Superdex 75. The lectin was absorbed on Affi-gel blue gel and desorbed using 1M NaCl in the starting buffer. Gel filtration on Superdex 75 yielded a major absorbance peak that gave a single 32-kDa band in SDS-PAGE. Hemagglutinating activity was completely preserved when the ambient temperature was in the range of 20 °C-60 °C. However, drastic reduction of the activity occurred at temperatures above 65 °C. Full hemagglutinating activity of the lectin was observed at an ambient pH of 3 to 12. About 50% activity remained at pH 0-2, and only residual activity was observed at pH 13-14. Hemagglutinating activity of the lectin was inhibited by glucosamine. The brown kidney bean lectin elicited maximum mitogenic activity toward murine splenocytes at 2.5 µM. The mitogenic activity was nearly completely eliminated in the presence of 250 mM glucosamine. The lectin also increased mRNA expression of the cytokines IL-2, TNF-α and IFN-γ. The lectin exhibited antiproliferative activity toward human breast cancer (MCF7) cells, hepatoma (HepG2) cells and nasopharyngeal carcinoma (CNE1 and CNE2) cells with IC(50) of 5.12 µM, 32.85 µM, 3.12 µM and 40.12 µM respectively after treatment for 24 hours. Flow cytometry with Annexin V and propidum iodide staining indicated apoptosis of MCF7 cells. Hoechst 33342 staining also indicated formation of apoptotic bodies in MCF7 cells after exposure to brown kidney bean lectin. Western blotting revealed that the lectin-induced apoptosis involved ER stress and unfolded protein response.

  19. Mitogenic and anti-proliferative activity of a lectin from the tubers of Voodoo lily (Sauromatum venosum).

    Science.gov (United States)

    Singh Bains, Jagmohan; Singh, Jatinder; Kamboj, Sukhdev Singh; Nijjar, Kamaljeet Kaur; Agrewala, Javed N; Kumar, Vinod; Kumar, Ashok; Saxena, A K

    2005-05-25

    A new lectin with the potent mitogenic and in vitro anti-proliferative activity was isolated from the tubers of a wild monocotyledonous plant Sauromatum venosum (Schott), from the family Araceae, by affinity chromatography on the asialofetuin linked amino-activated silica beads. The apparent native molecular mass of S. venosum lectin (SVL), as determined by gel filtration chromatography, was 54 kDa. In HPLC, size exclusion and cation exchange chromatography, SVL gave a single peak and also a single band of 13.5 kDa in SDS-PAGE, pH 8.3, under reducing and non-reducing conditions, indicating that the lectin is composed of four identical subunits. S. venosum lectin agglutinated rabbit, rat, sheep and guinea pig erythrocytes but reacted with goat erythrocytes after the neuraminidase treatment. However, SVL was unable to agglutinate human ABO blood group erythrocytes even after treatment with neuraminidase. SVL was inhibited by N-acetyl-D-Lactosamine (LacNAc), which is an important marker in various carcinomas and a complex desialylated glycoprotein, asialofetuin. The amino acid composition showed that lectin contained a high amount of aspartic acid and glycine but totally devoid of cysteine. However, trace amounts of methionine was present. The lectin showed a potent mitogenic response towards BALB/c splenocytes and human lymphocytes. As the mitogenic stimulation was more than that of Con A, a standard well-known plant mitogen and the response of this lectin was almost double than that of Con A. This lectin is endowed with proliferation of T cells as revealed by IL-2 bioassay but showed no production of immunoglobulins thus indicating the non-stimulation of B cells. SVL significantly inhibited the proliferation of murine cancer cell-lines, i.e., WEHI-279 to 84.6%, J774 to 81%, P388D1 to 74% and A-20 to 47%. In addition, the in vitro anti-proliferative activity of SVL was also evaluated against nine human cancer cell lines representing different organs and tissues

  20. New catechol derivatives of safrole and their antiproliferative activity towards breast cancer cells.

    Science.gov (United States)

    Madrid Villegas, Alejandro; Espinoza Catalán, Luis; Montenegro Venegas, Iván; Villena García, Joan; Carrasco Altamirano, Héctor

    2011-06-03

    Catechols were synthesized from safrole. Nine derivatives were prepared and assessed for antiproliferative effects using different human cell lines. The in vitro growth inhibition assay was based on the sulphorhodamine dye to quantify cell viability. The derivatives 4-allylbenzene-1,2-diol (3), 4 4-[3-(acetyloxy)propyl]-1,2-phenylene diacetate (6) and 4-[3-(acetyloxy)propyl]-5-nitro-1,2-phenylene diacetate (10) showed higher cytotoxicity than the parent compound 2 in tests performed on two breast cancer cell lines (MCF-7 and MDA-MB-231). The IC₅₀ values of 40.2 ± 6.9 μM, 5.9 ± 0.8 μM and 33.8 ± 4.9 μM, respectively, were obtained without toxicity towards dermal human fibroblast (DHF cells).

  1. A peptide with potent antifungal and antiproliferative activities from Nepalese large red beans.

    Science.gov (United States)

    Ma, D Z; Wang, H X; Ng, T B

    2009-12-01

    An antifungal defensin-like peptide with a molecular mass of 7.1kDa was isolated from dried Nepalese large red beans (Phaseolus angularis). The purification protocol employed included ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The antifungal peptide was unadsorbed on DEAE-cellulose, and adsorbed on Affi-gel blue gel and SP-Sepharose. The antifungal peptide inhibited mycelial growth in Fusarium oxysporum and Mycosphaerella arachidicola with an IC(50) value of 1.4 and 1.8 microM, respectively. It did not inhibit HIV-1 reverse transcriptase when tested up to 200 microM. It exerted an antiproliferative action on L1210 leukemia cells and MBL2 lymphoma cells with an IC(50) of 15 and 60 microM, respectively.

  2. Regulation of polyamine biosynthetic activity by spermidine and spermine analogs--a novel antiproliferative strategy.

    Science.gov (United States)

    Porter, C W; Bergeron, R J

    1988-01-01

    Interference with polyamine biosynthesis by analog-mediated regulatory mechanisms represents a viable alternative to the use of specific enzyme inhibitors as an antiproliferative strategy. The approach is unique among antimetabolite approaches and is made possible by unusual characteristics inherent to the polyamines and their biosynthetic pathway. Current antitumor data obtained with these analogs provides indication of their potential usefulness as antitumor agents but, at the same time, demonstrates the need for improvement. This latter might be attained by the rational design of analogs which (a) bind more tightly at enzyme regulatory sites, (b) which are less able to substitute for natural polyamines in growth related functions and (c) which are eliminated less rapidly from tumor-bearing animals. At the same time, the continued preclinical development of available analogs might proceed most productively by targeting large cell lung carcinoma and melanoma and by examining the generality of the relationship between oncogene expression and the accompanying sensitivity to regulatory analogs.

  3. New Catechol Derivatives of Safrole and Their Antiproliferative Activity towards Breast Cancer Cells

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    Héctor Carrasco Altamirano

    2011-06-01

    Full Text Available Catechols were synthesized from safrole. Nine derivatives were prepared and assessed for antiproliferative effects using different human cell lines. The in vitro growth inhibition assay was based on the sulphorhodamine dye to quantify cell viability. The derivatives 4-allylbenzene-1,2-diol (3, 4 4-[3-(acetyloxypropyl]-1,2-phenylene diacetate (6 and 4-[3-(acetyloxypropyl]-5-nitro-1,2-phenylene diacetate (10 showed higher cytotoxicity than the parent compound 2 in tests performed on two breast cancer cell lines (MCF-7 and MDA-MB-231. The IC50 values of 40.2 ± 6.9 μM, 5.9 ± 0.8 μM and 33.8 ± 4.9 μM, respectively, were obtained without toxicity towards dermal human fibroblast (DHF cells.

  4. Antiproliferative activities of lesser galangal (Alpinia officinarum Hance Jam1), turmeric (Curcuma longa L.), and ginger (Zingiber officinale Rosc.) against acute monocytic leukemia.

    Science.gov (United States)

    Omoregie, Samson N; Omoruyi, Felix O; Wright, Vincent F; Jones, Lemore; Zimba, Paul V

    2013-07-01

    Acute monocytic leukemia (AML M5 or AMoL) is one of the several types of leukemia that are still awaiting cures. The use of chemotherapy for cancer management can be harmful to normal cells in the vicinity of the target leukemia cells. This study assessed the potency of the extracts from lesser galangal, turmeric, and ginger against AML M5 to use the suitable fractions in neutraceuticals. Aqueous and organic solvent extracts from the leaves and rhizomes of lesser galangal and turmeric, and from the rhizomes only of ginger were examined for their antiproliferative activities against THP-1 AMoL cells in vitro. Lesser galangal leaf extracts in organic solvents of methanol, chloroform, and dichloromethane maintained distinctive antiproliferative activities over a 48-h period. The turmeric leaf and rhizome extracts and ginger rhizome extracts in methanol also showed distinctive anticancer activities. The lesser galangal leaf methanol extract was subsequently separated into 13, and then 18 fractions using reversed-phase high-performance liquid chromatography. Fractions 9 and 16, respectively, showed the greatest antiproliferative activities. These results indicate that the use of plant extracts might be a safer approach to finding a lasting cure for AMoL. Further investigations will be required to establish the discriminatory tolerance of normal cells to these extracts, and to identify the compounds in these extracts that possess the antiproliferative activities.

  5. Comparison of the antiproliferative activity of crude ethanol extracts of nine salvia species grown in Jordan against breast cancer cell line models

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    Rana Abu-Dahab

    2012-01-01

    Full Text Available Background: The antiproliferative activity of Salvia species grown in Jordan has not been fully evaluated yet. The aim of this work was to study the antiproliferative activity of crude ethanol extracts from nine Salvia species grown in Jordan against a panel of breast cancer cell lines. Material and Methods: Cytotoxic activity was evaluated in human tumor models of breast cancer; MCF-7, T47D, ZR-75-1, and BT 474 by the sulforhodamine B assay. In addition, the extracts were evaluated using a non-transformed cell line (Vero and normal fibroblast cells in order to demonstrate their selectivity and safety. Results: From the nice ethanol extracts under investigation, those of S. dominica and S. fruticosa showed an inhibitory concentration of 50% of cells (IC 50 in concentrations less than 30μg/mL against the four cell lines under investigation. S. syriaca and S. hormium showed an IC 50 below 30μg/ml for two out of the four cell lines. S. fruticosa, S. hormium and S. syriaca showed selectivity in their antiproliferative activity against estrogen receptor positive cell lines with minimal toxicity against normal human periodontal fibroblasts. Phytochemical screening using thin layer chromatography indicated the presence of terpenoids, flavonoids and coumarins in all examined extracts. Conclusion: Three of the plant extracts under investigation exhibited antiproliferative activity against breast cancer cells and were shown to be safe and selective. These could be considered as a potential source for novel anticancer therapy.

  6. Irinotecan Synergistically Enhances the Antiproliferative and Proapoptotic Effects of Axitinib In Vitro and Improves Its Anticancer Activity In Vivo

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    Bastianina Canu

    2011-03-01

    Full Text Available Aims: To demonstrate the synergistic antiproliferative and proapoptotic activity of irinotecan and axitinib in vitro and the improvement of the in vivo effects on angiogenesis and pancreatic cancer. Methods: Proliferation and apoptotic assays were performed on human dermal microvascular endothelial cells and pancreas cancer (MIAPaCa-2, Capan-1 cell lines exposed to SN-38, the active metabolite of irinotecan, axitinib, or their simultaneous combination for 72 hours. ERK1/2 and Akt phosphorylation, the vascular endothelial growth factor (VEGF, VEGF receptor-2, and thrombospondin-1 (TSP-1 concentration were measured by ELISAs. ATP7A and ABCG2 gene expression was performed with real-time polymerase chain reaction and SN-38 intracellular concentrations were measured by high-performance liquid chromatography. Capan-1 xenografts in nude mice were treated with irinotecan and axitinib alone or in simultaneous combination. Results: A strong synergistic effect on antiproliferative and proapoptotic activity was found with the axitinib/SN-38 combination on endothelial and cancer cells. ERK1/2 and Akt phosphorylation were significantly inhibited by lower concentrations of the combined drugs in all the cell lines. Axitinib and SN-38 combined treatment greatly inhibited the expression of the ATP7A and ABCG2 genes in endothelial and cancer cells, increasing the SN-38 intracellular concentration. Moreover, TSP-1 secretion was increased in cells treated with both drugs, whereas VEGFR-2 levels significantly decreased. In vivo administration of the simultaneous combination determined an almost complete regression of tumors and tumor neovascularization. Conclusions:In vitro results show the highly synergistic properties of simultaneous combination of irinotecan and axitinib on endothelial and pancreas cancer cells, suggesting a possible translation of this schedule into the clinics.

  7. Antiproliferative activity of mixed-ligand dien-Cu(II) complexes with thiazole, thiazoline and imidazole derivatives.

    Science.gov (United States)

    Bolos, C A; Papazisis, K T; Kortsaris, A H; Voyatzi, S; Zambouli, D; Kyriakidis, D A

    2002-01-01

    The reaction of [Cu(dien)NO(3)]NO(3) with 2-amino-5-methylthiazole (2A5MT), 2-amino-2-thiazoline (2A-2Tzn), imidazole (im), N,N'-thiocarbonyldiimidazole (Tcdim), 2-aminothiazole (2AT) and 2-ethylimidazole (2Etim), gave a new series of mixed-ligand compounds of the general formula [Cu(dien)(B)NO(3))]NO(3); (dien, diethylenetriamine; B, 2A5MT, 2A-2Tzn, im, Tcdim, 2AT and 2Etim). The complexes have been characterised by elemental analysis, molar conductivity and magnetic measurements, as well as by electronic and IR spectral studies. According to the above measurements the possible structure of the compounds is the square pyramidal in the solid state and the square planar in aqueous solution. We tested all complexes for antiproliferative (cytostatic and cytotoxic) activity against a panel of cell lines (HeLa, L929, HT-29 and T47D). All [(dien)Cu(B)NO(3))](NO(3)) complexes had an activity against colon cancer cells (HT-29), inducing G2/M cell cycle arrest, an effect that for most of the complexes could be attributed to p34cdc2 inhibition by tyrosine-phosphorylation and/or to induction of (cyclin-dependent kinase inhibitor) p21(WAF1). Other cell lines were resistant to the majority of the complexes, except [Cu(dien)(2A5MT)NO(3))](NO(3)), that had showed the highest anti-proliferative activity against HT-29 cells also. The predilection for colon cancer cells and the relatively low toxicity against normal (L929) cells justify further investigation of this group of compounds.

  8. Synthesis, crystal structure determination and antiproliferative activity of novel 2-amino-4-aryl-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazoles

    Science.gov (United States)

    Hranjec, Marijana; Pavlović, Gordana; Karminski-Zamola, Grace

    2012-01-01

    This manuscript describes the synthesis of novel 2-amino-4-aryl-4,10-dihydro-[1,3,5]triazino[1,2- a]benzimidazoles as hydrochloride salts 4a-n and 5b which were prepared in the reaction of cyclocondensation between 2-guanidinobenzimidazole and versatile heteroaromatic aldehydes. Structures of all prepared compounds have been studied by using 1H and 13C NMR, IR and UV/Vis spectroscopy. The crystal and molecular structure of 4f was determined by X-ray diffraction on single crystals. The molecule of 2-amino-4-(4'-methylphenyl)-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole hydrochloride 4f (C 16H 16N 5+·Cl -) exists in the solid state in one of the possible tautomeric forms, being protonated at the one of the nitrogen atoms of the 1,4-dihydrotriazine ring. The molecule is highly delocalized within the 4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole moiety with the highest deviation from the plane for the methine carbon atom and the protonated nitrogen atom of the 1,4-dihydrotriazine ring. The cations are joined via N-H⋯N hydrogen bonds into R22(8) centrosymmetric dimers. Cation dimers are further connected with Cl - ions via N-H⋯Cl and C-H⋯Cl hydrogen bonds into 2D chains spreading along the b axis. The obtained single-crystal X-ray structure determination unequivocally confirms tautomeric form of the compound present in the solid-state and can represent tantative pattern for other prepared compounds. All prepared compounds were tested on their antiproliferative activity in vitro on several human cancer cell lines. Compound 4m was the most active one (IC 50 ≈ 20 μM), while compounds 4d, 4f, 4k, 4l4m showed moderate, but non-selective, antiproliferative activity with IC 50 25-60 μM.

  9. Antiproliferative Pt(IV) complexes: synthesis, biological activity, and quantitative structure-activity relationship modeling.

    Science.gov (United States)

    Gramatica, Paola; Papa, Ester; Luini, Mara; Monti, Elena; Gariboldi, Marzia B; Ravera, Mauro; Gabano, Elisabetta; Gaviglio, Luca; Osella, Domenico

    2010-09-01

    Several Pt(IV) complexes of the general formula [Pt(L)2(L')2(L'')2] [axial ligands L are Cl-, RCOO-, or OH-; equatorial ligands L' are two am(m)ine or one diamine; and equatorial ligands L'' are Cl- or glycolato] were rationally designed and synthesized in the attempt to develop a predictive quantitative structure-activity relationship (QSAR) model. Numerous theoretical molecular descriptors were used alongside physicochemical data (i.e., reduction peak potential, Ep, and partition coefficient, log Po/w) to obtain a validated QSAR between in vitro cytotoxicity (half maximal inhibitory concentrations, IC50, on A2780 ovarian and HCT116 colon carcinoma cell lines) and some features of Pt(IV) complexes. In the resulting best models, a lipophilic descriptor (log Po/w or the number of secondary sp3 carbon atoms) plus an electronic descriptor (Ep, the number of oxygen atoms, or the topological polar surface area expressed as the N,O polar contribution) is necessary for modeling, supporting the general finding that the biological behavior of Pt(IV) complexes can be rationalized on the basis of their cellular uptake, the Pt(IV)-->Pt(II) reduction, and the structure of the corresponding Pt(II) metabolites. Novel compounds were synthesized on the basis of their predicted cytotoxicity in the preliminary QSAR model, and were experimentally tested. A final QSAR model, based solely on theoretical molecular descriptors to ensure its general applicability, is proposed.

  10. Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines with potent photo-antiproliferative activity.

    Science.gov (United States)

    Spanò, Virginia; Giallombardo, Daniele; Cilibrasi, Vincenzo; Parrino, Barbara; Carbone, Anna; Montalbano, Alessandra; Frasson, Ilaria; Salvador, Alessia; Richter, Sara N; Doria, Filippo; Freccero, Mauro; Cascioferro, Stella; Diana, Patrizia; Cirrincione, Girolamo; Barraja, Paola

    2017-03-10

    Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines were synthesized as a new class of tricyclic system in which the pyridine ring is annelated to a cycloheptapyrrole scaffold, with the aim of obtaining new photosensitizing agents with improved antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached, which allowed the isolation of derivatives of the title ring system with a good substitution pattern on the pyrrole moiety. Photobiological studies revealed that the majority of the new compounds showed a potent cytotoxic effect upon photoactivation with light of the proper wavelength, especially when decorated with a 2-ethoxycabonyl group and a N-benzyl substituted moiety, with EC50 values reaching the submicromolar level. The mechanism of action was evaluated.

  11. ANTIPROLIFERATIVE ACTIVITY OF ETHANOLIC FLOWER EXTRACT FROM NYMPHAEA PUBESCENS WILLD AGAINST HUMAN CERVICAL AND BREAST CARCINOMA IN VITRO

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    Selvakumari E

    2012-01-01

    Full Text Available Nymphaea pubescens Willd (Nymphaeaceae is a fascinating aquatic plant mentioned in siddha system of medicine, in the treatment of bleeding piles, diabetes and as cardiotonic in palpitation of the heart. Nymphaea species was traditionally used for treating cancer. The present study was designed to evaluate the invitro antiproliferative activity of Nymphaea pubescens Willd. The ethanolic extract of different parts such as rhizome, leaf, flower and fruit was subjected for MTT assay. The ethanolic extract of flower part was found to be cytotoxic against human cervical carcinoma Hela cell lines and human breast carcinoma MCF cell lines. The IC50 value of ethanolic flower extract was 91.57µg/ml against Hela cell lines and 99.6µg/ml against MCF-7 cell lines. Significant results were observed thereby justifying the use of plant in the traditional system of medicine.

  12. Osmium(IV) complexes with 1H- and 2H-indazoles: tautomer identity versus spectroscopic properties and antiproliferative activity.

    Science.gov (United States)

    Büchel, Gabriel E; Stepanenko, Iryna N; Hejl, Michaela; Jakupec, Michael A; Keppler, Bernhard K; Heffeter, Petra; Berger, Walter; Arion, Vladimir B

    2012-08-01

    A one-pot synthesis of osmium(IV) complexes with two different tautomers of indazole, 1H-indazole and 2H-indazole, namely (H(2)ind)[Os(IV)Cl(5)(2H-ind)] (1) and (H(2)ind)[Os(IV)Cl(5)(1H-ind)] (2) is reported. Both compounds have been comprehensively characterized by NMR spectroscopy, ESI (electrospray ionization) mass spectrometry, electronic absorption spectroscopy, IR spectroscopy, cyclic voltammetry and tested for antiproliferative activity in vitro in three human cancer cell lines, CH1 (ovarian carcinoma), A549 (non-small cell lung cancer) and SW480 (colon carcinoma), as well as in vivo in a Hep3B SCID mouse xeno-transplantation model. 2H-Indazole tautomer stabilization in 1 has been confirmed by X-ray diffraction.

  13. EGb-761 Attenuates the Anti-proliferative Activity of Fluoride via DDK1 in PC-12 Cells.

    Science.gov (United States)

    Zhang, Cai-Yi; Chen, Rui; Wang, Fen; Ren, Chao; Zhang, Peng; Li, Qian; Li, Hui-Hua; Guo, Ke-Tai; Geng, De-Qin; Liu, Chun-Feng

    2017-02-01

    EGb-761 is commonly used as a treatment for ischemic brain injury, neurodegenerative diseases and some types of tumors (Christen and Maixent, in Cell Mol Biol 48(6):601-611, 2002). However, it is unclear whether EGb-761 affects the proliferation of cells exposed to fluoride. In this study, the proliferation and apoptosis of PC-12 cells exposed to fluoride were investigated and EGb-761 was used to protect PC-12 cells against the effects of fluoride. We found that the canonical Wnt signaling pathway was involved in the anti-proliferation of PC-12 cells exposed to fluoride. Furthermore, the results also showed that EGb-761 could attenuate the anti-proliferative activity of fluoride via DDK1 in PC-12 cells. This study may provide a new method for protecting against the inhibition of cell proliferation induced by fluoride.

  14. Limitations of MTT and MTS-based assays for measurement of antiproliferative activity of green tea polyphenols.

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    Piwen Wang

    Full Text Available BACKGROUND: The chemopreventive effect of green tea polyphenols, such as (--epigallocatechin-3-gallate (EGCG, has been well demonstrated in cell culture studies. However, a wide range of IC(50 concentrations has been observed in published studies of the anti-proliferative activity of EGCG from different laboratories. Although the susceptibility to EGCG treatment is largely dependent on cancer cell type, the particular cell viability and proliferation assays utilized may significantly influence quantitative results reported in the literature. METHODOLOGY/PRINCIPAL FINDINGS: We compared five widely used methods to measure cell proliferation and viability after EGCG treatment using LNCaP prostate cancer cells and MCF-7 breast cancer cells. Both methods using dyes to quantify adenosine triphosphate (ATP and deoxynucleic acid (DNA showed accuracy in the measurement of viable cells when compared to trypan blue assay and results showed good linear correlation (r = 0.95. However, the use of MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and MTS (3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium as indicators of metabolically active mitochondria overestimated the number of viable cells by comparison with the ATP, DNA, or trypan blue determinations. As a result, the observed IC(50 concentration of EGCG was 2-fold higher using MTT and MTS compared to dyes quantifying ATP and DNA. In contrast, when cells were treated with apigenin MTT and MTS assays showed consistent results with ATP, DNA, or trypan blue assays. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that MTT and MTS -based assays will provide an underestimation of the anti-proliferative effect of EGCG, and suggest the importance of careful evaluation of the method for in vitro assessment of cell viability and proliferation depending on the chemical nature of botanical supplements.

  15. Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

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    Anna Piotrowska

    2016-01-01

    Full Text Available Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM analogs of 1,25-dihydroxyvitamin D2 (1,25(OH2D2 induced differentiation of the vitamin D receptor (VDR positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl and in the A-ring (5,6-trans modification, the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM. Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs.

  16. Studies on phytochemical, antioxidant, anti-inflammatory, hypoglycaemic and antiproliferative activities of Echinacea purpurea and Echinacea angustifolia extracts.

    Science.gov (United States)

    Aarland, Rayn Clarenc; Bañuelos-Hernández, Angel Ernesto; Fragoso-Serrano, Mabel; Sierra-Palacios, Edgar Del Carmen; Díaz de León-Sánchez, Fernando; Pérez-Flores, Laura Josefina; Rivera-Cabrera, Fernando; Mendoza-Espinoza, José Alberto

    2017-12-01

    Echinacea (Asteraceae) is used because of its pharmacological properties. However, there are few studies that integrate phytochemical analyses with pharmacological effects. Evaluate the chemical profile and biological activity of hydroalcoholic Echinacea extracts. Density, dry matter, phenols (Folin-Ciocalteu method), flavonoids (AlCl3 method), alkylamides (GC-MS analysis), antioxidant capacity (DPPH and ABTS methods), antiproliferative effect (SRB assay), anti-inflammatory effect (paw oedema assay, 11 days/Wistar rats; 0.4 mL/kg) and hypoglycaemic effect (33 days/Wistar rats; 0.4 mL/kg) were determined in three Echinacea extracts which were labelled as A, B and C (A, roots of Echinacea purpurea L. Moench; B, roots, leaves, flowers and seeds of Echinacea purpurea; C, aerial parts and roots of Echinacea purpurea and roots of Echinacea angustifolia DC). Extract C showed higher density (0.97 g/mL), dry matter (0.23 g/mL), phenols (137.5 ± 2.3 mEAG/mL), flavonoids (0.62 ± 0.02 mEQ/mL), and caffeic acid (0.048 mg/L) compared to A and B. A, B presented 11 alkylamides, whereas C presented those 11 and three more. B decreased the oedema (40%) on day 2 similar to indomethacin. A and C showed hypoglycaemic activity similar to glibenclamide. Antiproliferative effect was only detected for C (IC50 270 μg/mL; 8171 μg/mL; 9338 μg/mL in HeLa, MCF-7, HCT-15, respectively). The difference in the chemical and pharmacological properties among extracts highlights the need to consider strategies and policies for standardization of commercial herbal extracts in order to guarantee the safety and identity of this type of products.

  17. Antiproliferative activity of flower hexane extract obtained from Mentha spicata associated with Mentha rotundifolia against the MCF7, KB, and NIH/3T3 cell lines.

    Science.gov (United States)

    Nedel, Fernanda; Begnini, Karine; Carvalho, Pedro Henrique de Azambuja; Lund, Rafael Guerra; Beira, Fátima T A; Del Pino, Francisco Augusto B

    2012-11-01

    This study assessed the antiproliferative effect in vitro of the flower hexane extract obtained from Mentha spicata associated with Mentha rotundifolia against the human breast adenocarcinoma (MCF-7), human mouth epidermal carcinoma (KB), and mouse embryonic fibroblast (NIH 3T3) cell lines, using sulforhodamine B (SRB) assay. A cell density of 2×10(4)/well was seeded in 96-well plates, and samples at different concentrations ranging from 10 to 500 mg/mL were tested. The optical density was determined in an ELISA multiplate reader (Thermo Plate TP-Reader). Results demonstrated that the hexane extract presented antiproliferative activity against both the tumor cell lines KB and MCF-7, presenting a GI(50) (MCF-7=13.09 mg/mL), TGI (KB=37.76 mg/mL), and IL(50) (KB=291.07 mg/mL). Also, the hexane extract presented antiproliferative activity toward NIH 3T3 cells GI(50) (183.65 mg/mL), TGI (280.54 mg/mL), and IL(50) (384.59 mg/mL). The results indicate that the flower hexane extract obtained from M. spicata associated with M. rotundifolia presents an antineoplastic activity against KB and MCF-7, although an antiproliferative effect at a high concentration of the extract was observed toward NIH 3T3.

  18. Anti-Oxidative and Anti-Proliferative Activity on Human Prostate Cancer Cells Lines of the Phenolic Compounds from Corylopsis coreana Uyeki

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    So Ra Kim

    2013-04-01

    Full Text Available Fifteen phenolic compounds, including three caffeoyl derivatives, four gallotannins, three ellagitannins and five flavonoids, were isolated from an 80% MeOH extract of the leaves of Corylopsis coreana Uyeki (Korean winter hazel; CL. The anti-oxidative activities [1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging activity and xanthine oxidase superoxide scavenging activities (NBT] and the anti-proliferative activity on human prostate cancer cell lines (DU145 and LNCaP were also evaluated.

  19. Bacterial ghosts as novel advanced drug delivery systems: antiproliferative activity of loaded doxorubicin in human Caco-2 cells.

    Science.gov (United States)

    Paukner, Susanne; Kohl, Gudrun; Lubitz, Werner

    2004-01-08

    Systemic application of anticancer drugs often causes severe toxic side effects. To reduce the undesired effects, advanced drug delivery systems are needed which are based on specific cell targeting vehicles. In this study, bacterial ghosts from Mannheimia haemolytica were used for site-specific delivery of doxorubicin (DOX) to human colorectal adenocarcinoma cells (Caco-2). Bacterial ghosts are non-denatured envelopes of Gram-negative bacteria with fully intact surface structures for specific attachment to mammalian cells. The in vitro release profile of DOX-ghosts demonstrated that the loaded drug was non-covalently associated with the bacterial ghosts and that the drug delivery vehicles themselves represent a slow release system. Adherence studies showed that the M. haemolytica ghosts more efficiently than E. coli ghosts targeted the Caco-2 cells and released the loaded DOX within the cells. Cytotoxicity assays revealed that the DOX-ghosts exhibited potent antiproliferative activities on Caco-2 cells as the DOX associated with ghosts was two magnitude of orders more cytotoxic than free DOX provided in the medium at the same concentrations. Notably, a significant reduction in the cell viability was measured with DOX-ghosts at low DOX concentrations, which had no inhibitory effect when applied as free DOX after incubation for 16 h or when applied at higher concentrations for only 10 min to the cells. As the higher antiproliferative effects of DOX on Caco-2 cells were mediated by the specific drug targeting properties of the bacterial ghosts, the bacterial ghost system represents a novel platform for advanced drug delivery.

  20. Novel third-generation water-soluble noscapine analogs as superior microtubule-interfering agents with enhanced antiproliferative activity.

    Science.gov (United States)

    Henary, Maged; Narayana, Lakshminarayana; Ahad, Shazia; Gundala, Sushma R; Mukkavilli, Rao; Sharma, Vibhuti; Owens, Eric A; Yadav, Yogesh; Nagaraju, Mulpuri; Hamelberg, Donald; Tandon, Vibha; Panda, Dulal; Aneja, Ritu

    2014-11-15

    Noscapine, an opium-derived 'kinder-gentler' microtubule-modulating drug is in Phase I/II clinical trials for cancer chemotherapy. However, its limited water solubility encumbers its development into an oral anticancer drug with clinical promise. Here we report the synthesis of 9 third-generation, water-soluble noscapine analogs with negatively charged sulfonato and positively charged quaternary ammonium groups using noscapine, 9-bromonoscapine and 9-aminonoscapine as scaffolds. The predictive free energy of solvation was found to be lower for sulfonates (6a-c; 8a-c) compared to the quaternary ammonium-substituted counterparts, explaining their higher water solubility. In addition, sulfonates showed higher charge dispersability, which may effectively shield the hydrophobicity of isoquinoline nucleus as indicated by hydrophobicity mapping methods. These in silico data underscore efficient net charge balancing, which may explain higher water solubility and thus enhanced antiproliferative efficacy and improved bioavailability. We observed that 6b, 8b and 8c strongly inhibited tubulin polymerization and demonstrated significant antiproliferative activity against four cancer cell lines compared to noscapine. Molecular simulation and docking studies of tubulin-drug complexes revealed that the brominated compound with a four-carbon chain (4b, 6b, and 8b) showed optimal binding with tubulin heterodimers. Interestingly, 6b, 8b and 8c treated PC-3 cells resulted in preponderance of mitotic cells with multipolar spindle morphology, suggesting that they stall the cell cycle. Furthermore, in vivo pharmacokinetic evaluation of 6b, 8b and 8c revealed at least 1-2-fold improvement in their bioavailability compared to noscapine. To our knowledge, this is the first report to demonstrate novel water-soluble noscapine analogs that may pave the way for future pre-clinical drug development.

  1. Antiproliferative activity and nitric oxide production of a methanolic extract of Fraxinus micrantha on Michigan Cancer Foundation-7 mammalian breast carcinoma cell line

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    Suresh Kumar

    2015-06-01

    Full Text Available Aim:Methanolic extract of aFraxinus micrantha(MeFM was evaluated for antiproliferative activity in vitrousing Michigan Cancer Foundation-7 (MCF-7 breast carcinoma cell line. This plant was selected and studied for naturally available bioactive compound as different synthetic drugs available for cancer treatment has certain limitations and side effects. Materials and Methods:The anti-proliferative activity of a methanolic extract from the aerial parts of F. micranthawas assessed on MCF-7 breast cancer cell line using 3(4,5-dimethylthiazol-2-yl2,5-diphenyl-tetrazolium bromide assay. Furthermore, to understand the mechanism of anti-proliferation, production of nitric oxide (NO and DNA fragmentation was also determined on MCF-7 cells. Different phytoconstituents of the extract were determined qualitatively based on various biochemical assays. Results: The results demonstrated anti-proliferative activity of an MeFM in a concentration and time-dependent manner. The percentage viability determined was 31.24% at 125 and #956;g/ml as compared to 80.46% in negative control group. An MeFM has also shown NO production in a concentration (0.2-125 and #956;g/ml and time-dependent manner (24-48 h. DNA fragmentation studies showed that a methanolic extract was causing DNA fragmentation thus inducing apoptosis in MCF-7 breast carcinoma cells. Biochemical analysis result showed the presence of flavonoids, polyphenols, and sterols in an MeFM. Conclusion:In conclusion, F. micranthapossesses potent anti-proliferative activity on the malignant MCF-7 cell line which is correlated with the production of NO and DNA fragmentation. Further studies are required to identify, isolate, and characterize the phytochemicals present in the methanolic extract that might have antiproliferative potential in the treatment of different cancer conditions. [J Intercult Ethnopharmacol 2015; 4(2.000: 109-113

  2. Antiproliferative and Proapoptotic Activities of Methanolic Extracts from Ligustrum vulgare L. as an Individual Treatment and in Combination with Palladium Complex

    Directory of Open Access Journals (Sweden)

    Snežana D. Marković

    2012-02-01

    Full Text Available The aim of this study is to examine the growth inhibitory effects of methanolic leaf and fruit extracts of L. vulgare on HCT-116 cells over different time periods and their synergistic effect with a Pd(apox complex. The antiproliferative activity of plant extracts alone or in combination with the Pd(apox complex was determined using MTT cell viability assay, where the IC50 value was used as a parameter of cytotoxicity. Results show that antiproliferative effects of L. vulgare extracts increase with extension of exposure time, with decreasing IC50 values, except for 72 h where the IC50 values for methanolic leaf extract were lower than for the fruit extract. The Pd(apox complex alone had a weak antiproliferative effect, but combination with L. vulgare extracts caused stronger effects with lower IC50 values than with L. vulgare extracts alone. The type of cell death was explored by fluorescence microscopy using the acridin orange/ethidium bromide method. Treatments with plant extracts caused typical apoptotic morphological changes in HCT-116 cells and co-treatments with Pd(apox complex caused higher levels of apoptotic cells than treatment with plant extracts alone. The results indicate that L. vulgare is a considerable source of natural bioactive substances with antiproliferative activity on HCT-116 cells and which have a substantial synergistic effect with the Pd(apox complex.

  3. Anti-proliferative and antioxidative activities of Thai noni/Yor (Morinda citrifolia Linn.) leaf extract.

    Science.gov (United States)

    Thani, Wasina; Vallisuta, Omboon; Siripong, Pongpan; Ruangwises, Nongluck

    2010-03-01

    In this study the leaves of the Thai noni/Yor, (Morinda citrifolia Linn.) were extracted by several methods and evaluated against human cancer cell lines: KB (human epidermoid carcinoma), HeLa (human cervical carcinoma), MCF-7 (human breast carcinoma) and HepG2 (human hepatocellular carcinoma) cell lines as well as a Vero (African green monkey kidney) cell line, employing the MTT colorimetric method, comparing it to damnacanthal, rutin, and scopoletin. The dichloromethane extract of the fresh leaf showed a better inhibitory effect against KB and HeLa cells with IC50 values of 21.67 and 68.50 microg/ml, respectively. The dichloromethane extract of dried leaves revealed cytotoxicity against the KB cell line with an IC50 value of 39.00 microg/ml. Other extracts, as well as rutin and scopoletin, showed reduced anti-proliferative effects on all cancer cell lines (IC50 103 to over 600 microg/ml). Interestingly, the damnacanthal had potent cytotoxicity against all cancer cell lines and Vero cell lines. These results suggest Thai noni extracts may be safer than the pure compounds, due to their higher safety ratios, which is a good indicator for possible cancer treatment. Several non-aqueous extracts from the leaves showed antioxidant properties, giving IC50 values of 0.20-0.35 mg/ml. It can be concluded the leaves of M. citrifolia may have benefit as a food supplement for chemoprevention against epidermoid and cervical cancers.

  4. Astersedifolioside A-C, three new oleane-type saponins with antiproliferative activity.

    Science.gov (United States)

    Corea, Gabriella; Iorizzi, Maria; Lanzotti, Virginia; Cammareri, Maria; Conicella, Clara; Laezza, Chiara; Bifulco, Maurizio

    2004-09-15

    A phytochemical analysis of Aster sedifolius has led to the isolation of three novel triterpenoid saponins, based on an oleane-type skeleton and named astersedifolioside A (1), B (2) and C (3). On the basis of chemical, and 2D NMR and mass spectrometry data, the structures of the new compounds were elucidated as 3-O-[alpha-L-rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl] echinocystic acid 28-[O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranoside] (1), 3-O-[alpha-L-rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl] echinocystic acid 28-[O-beta-D-xylopyranosyl (1-->4)-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranoside] (2) and 3-O-[alpha-L-rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranosyl] echinocystic acid 28-[O-beta-D-xylopyranosyl (1-->4)-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranoside] (3). The isolated compounds showed antiproliferative effect in KiMol, a transformed thyroid cell line.

  5. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines.

    Science.gov (United States)

    Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Shuji

    2014-03-01

    Although lycopene, a major carotenoid component of tomatoes, has been suggested to attenuate the risk of breast cancer, the underlying preventive mechanism remains to be determined. Moreover, it is not known whether there are any differences in lycopene activity among different subtypes of human breast cancer cells. Using ER/PR positive MCF-7, HER2-positive SK-BR-3 and triple-negative MDA-MB-468 cell lines, we investigated the cellular and molecular mechanism of the anticancer activity of lycopene. Lycopene treatment for 168 consecutive hours exhibited a time-dependent and dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0 /G1 phase at physiologically achievable concentrations found in human plasma. The greatest growth inhibition was observed in MDA-MB-468 where the sub-G0 /G1 apoptotic population was significantly increased, with demonstrable cleavage of PARP. Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines. In triple negative cells, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax without affecting anti-apoptotic Bcl-xL. Taken together, these data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells suggests a potential role of lycopene for the prevention of triple negative breast cancer.

  6. Composition, antibacterial, antioxidant and antiproliferative activities of essential oils from three Origanum species growing wild in Lebanon and Greece.

    Science.gov (United States)

    Marrelli, Mariangela; Conforti, Filomena; Formisano, Carmen; Rigano, Daniela; Arnold, Nelly Apostolides; Menichini, Francesco; Senatore, Felice

    2016-01-01

    The essential oils from Origanum dictamnus, Origanum libanoticum and Origanum microphyllum were analysed by GC-MS, finding carvacrol, p-cymene, linalool, γ-terpinene and terpinen-4-ol as major components. The antioxidant activity by the DPPH and FRAP tests and the antiproliferative activity against two human cancer cell lines, LoVo and HepG2, were investigated, showing that the essential oil of O. dictamnus was statistically the most inhibitory on both the cell lines, while all the oils exerted a weak antioxidant activity. Furthermore, the samples were tested against 10 Gram-negative and Gram-positive bacteria; all the oils were active on Gram-positive bacteria but O. dictamnus essential oil was the most effective (MIC = 25-50 μg/mL), showing also a good activity against the Gram-negative Escherichia coli (MIC = 50 μg/mL). Data suggest that these essential oils and particularly O. dictamnus oil could be used as valuable new flavours with functional properties for food or nutraceutical products.

  7. Purification and Characterization of a Mannose-binding Lectin from the Rhizomes of Aspidistra elatior Blume with Antiproliferative Activity

    Institute of Scientific and Technical Information of China (English)

    Xiaochao XU; Chuanfang WU; Chao LIU; Yongting LUO; Jian LI; Xinping ZHAO; Els Van DAMME; Jinku BAO

    2007-01-01

    A lectin with a novel N-terminal amino acid sequence was purified from the rhizomes of Aspidistra elatior Blume by ammonium sulphate precipitation, ion exchange chromatography on diethylaminoethyl-Sepharose and carboxymethyl-Sepharose and gel filtration chromatography on Sephacryl S-100. The A. elatior Blume lectin (AEL) is a heterotetramer with a molecular mass of 56 kDa and composed of two homodimers consisting of two different polypeptides of 13.5 kDa and 14.5 kDa held together by noncovalent interactions. Hapten inhibition assay indicated that hemagglutinating activity of AEL towards rabbit erythrocytes could be inhibited by D-mannose, mannan, thyroglobulin and ovomucoid. The lectin was stable up to 70 ℃, and showed maximum activity in a narrow pH range of 7.0-8.0. Chemical modification and spectrum analysis indicated that tryptophan, arginine, cysteine and carboxyl group residues were essential for its hemagglutinating activity. However, they might not be present in the active center, except some carboxyl group residues. AEL also showed significant in vitro antiproliferative activity towards Bre-04 (66%),Lu-04 (60%) and HepG2 (56%) of human cancer cell lines.

  8. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity.

    Science.gov (United States)

    Kontogianni, Vassiliki G; Tomic, Goran; Nikolic, Ivana; Nerantzaki, Alexandra A; Sayyad, Nisar; Stosic-Grujicic, Stanislava; Stojanovic, Ivana; Gerothanassis, Ioannis P; Tzakos, Andreas G

    2013-01-01

    The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MS(n)). For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid. Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells. Decrease of RINm5F viability was mediated by nitric oxide (NO)-induced apoptosis. Importantly, these extracts potentiated NO and TNF-α release from macrophages therefore enhancing their cytocidal action. The rosemary extract developed more pronounced antioxidant, cytotoxic and immunomodifying activities, probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile.

  9. Fucans, sulfated polysaccharides extracted from brown seaweeds, inhibit vascular smooth muscle cell proliferation. I. Comparison with heparin for antiproliferative activity, binding and internalization.

    Science.gov (United States)

    Logeart, D; Prigent-Richard, S; Jozefonvicz, J; Letourneur, D

    1997-12-01

    Smooth muscle cell (SMC) proliferation is inhibited both in vivo and in vitro by heparin. However, the precise mechanisms of action are still not understood. The analogy between two sulfated polysaccharides, heparin and fucan, has led us to compare in detail their effects on SMC growth. We have prepared and characterized a 19 kDa fucan fraction from brown seaweed, Ascophyllum nodosum. Fucan affects the growth of SMCs in a time- and dose-dependent, reversible and non-toxic fashion. As determined by cell counting, [3H]thymidine incorporation, and microcytofluorimetry analysis, heparin was less active than fucan in inhibiting SMC growth. Fucan and heparin act by preferential blocking of G0/G1, thus decreasing the G0/S transition. Binding experiments with [125I]fucan indicated saturable, unlabeled-fucan displaceable binding sites with an apparent Kd of 30 nM. Moreover, displacement experiments performed with various polysaccharides revealed that antiproliferative compounds interacted with these membrane sites, but non-antiproliferative polysaccharides (dextran, chondroitin sulfate) did not, providing evidence of a correlation between binding to SMCs and their antiproliferative activity. When cells were exposed at 37 degrees C to a fluorescent 5-([4,6-dichlorotriazin-2-yl]-amino)fluorescein (DTAF)-fucan, internalization occurred and punctate vesicles were observed which accumulated rapidly in the perinuclear region as previously reported for heparin. Nuclear preparations (membranes + contents) of cultured SMCs previously incubated with radiolabeled heparin or fucan indicated the presence of radioactivity, suggesting an antiproliferative action of both polysaccharides at the nuclear level. Collectively, these observations indicated that fucan and heparin share some similar mechanisms of action, such as SMC growth inhibition, binding, and internalization. In the accompanying paper (Logeart et al., Eur. J. Cell Biol. 74, 1997, this issue), we describe the effect of fucans

  10. Investigation of the Lignan Content in Extracts from Linum, Callitris and Juniperus Species in Relation to Their In Vitro Antiproliferative Activities.

    Science.gov (United States)

    Doussot, Joël; Mathieu, Véronique; Colas, Cyril; Molinié, Roland; Corbin, Cyrielle; Montguillon, Josiane; Moreno Y Banuls, Laeticia; Renouard, Sullivan; Lamblin, Frédéric; Dupré, Patricia; Maunit, Benoit; Kiss, Robert; Hano, Christophe; Lainé, Eric

    2017-04-01

    Podophyllotoxin, a lignan still extracted from the rhizomes of Podophyllum hexandrum (Berberidaceae), is the starting molecule for the semisynthesis of widely used anticancer drugs such as etoposide. However, this source is threatened by the over-collection of P. hexandrum. Plants belonging to the Linaceae and Cupressaceae families could be attractive alternative sources with species that contain the lignan podophyllotoxin or its precursors and derivatives. Wild flax species, such as Linum flavum, as well as some Juniperus and Callitris species were investigated for their lignan content, and the in vitro antiproliferative capacity of their extracts was assayed on four tumor cell lines. Some of the lignans were detected by LC-HRMS for the first time in these extracts.In addition, lignans purified from these plants and compounds semisynthesized from commercially available podophyllotoxin were tested in terms of their in vitro antiproliferative activity. The genus Juniperus was the most promising given its in vitro antiproliferative effects, which were also observed with extracts from L. flavum and Callitris species.The in vitro antiproliferative effect of the plant extracts studied here appears to correlate well with the contents of the aryltetralin lignan podophyllotoxin and its glycoside as well as with deoxypodophyllotoxin and 6-methoxypodophyllotoxin. The strongest correlation between the lignan content of the extracts and the antiproliferative activity was observed for 6-methoxypodophyllotoxin. Regarding the possibility of producing large renewable amounts of 6-methoxypodophyllotoxin, this molecule could be of interest to produce new anticancer drugs and to bypass the resistance mechanisms against podophyllotoxin-derived drugs. Georg Thieme Verlag KG Stuttgart · New York.

  11. Biological Characterization of Cynara cardunculus L. Methanolic Extracts: Antioxidant, Anti-proliferative, Anti-migratory and Anti-angiogenic Activities

    Directory of Open Access Journals (Sweden)

    Maria Duarte

    2012-12-01

    Full Text Available Cynara cardunculus (Cc is a multipurpose species; beyond its use in southwestern European cuisine, it is also used for the production of solid biofuel, seed oil, biodiesel, paper pulp and cheese, as well as animal feed. In addition, Cc has a long tradition of use in folk medicine as a diuretic and liver protector. The value of this species as a source of bioactive compounds is known; however, pharmacological use would further increase its cultivation. The main goal of the current work was to evaluate the potential of Cc as source of anti-carcinogenic phytochemicals. Different methanolic extracts obtained from wild and cultivated plants were tested for antioxidant activity and effect on breast tumor cell viability. The most effective extract, both as antioxidant and inhibition of tumor cell viability, was tested for effects on angiogenesis and tumor cell migration capacity. All the extracts tested had high antioxidant activity; however, only green leaves and dry head extracts exhibit anti-proliferative activity. Green cultivated leaves (GCL were the most effective extract both as antioxidant and inhibiting the proliferation of tumor cells; it is equally active inhibiting tumor cell migration and in vivo angiogenesis. GCL extract is an effective inhibitor of several key points in tumor development and thus a promising source of anti-carcinogenic phytochemicals.

  12. Bark extract mediated green synthesis of silver nanoparticles: Evaluation of antimicrobial activity and antiproliferative response against osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Debasis; Ashe, Sarbani; Rauta, Pradipta Ranjan; Kumari, Manisha; Nayak, Bismita, E-mail: nayakb@nitrkl.ac.in

    2016-01-01

    In the current investigation we report the biosynthesis potentials of bark extracts of Ficus benghalensis and Azadirachta indica for production of silver nanoparticle without use of any external reducing or capping agent. The appearance of dark brown color indicated the complete nanoparticle synthesis which was further validated by absorbance peak by UV–vis spectroscopy. The morphology of the synthesized particles was characterized by Field emission- scanning electron microscopy (Fe-SEM) and atomic force microscopy (AFM). The X-ray diffraction (XRD) patterns clearly illustrated the crystalline phase of the synthesized nanoparticles. ATR-Fourier Transform Infrared (ATR-FTIR) spectroscopy was performed to identify the role of various functional groups in the nanoparticle synthesis. The synthesized nanoparticles showed promising antimicrobial activity against Gram negative (Escherichia coli, Pseudomonas aeruginosa and Vibrio cholerae) and Gram positive (Bacillus subtilis) bacteria. The synthesized nano Ag also showed antiproliferative activity against MG-63 osteosarcoma cell line in a dose dependent manner. Thus, these synthesized Ag nanoparticles can be used as a broad spectrum therapeutic agent against osteosarcoma and microorganisms. - Highlights: • Rapid, cost effective, benign synthesis of AgNPs using novel bark extracts • Color change and absorbance peak observed at 426 and 420 nm due to SPR phenomenon • Crystalline and spherical nanoparticles having average size of ~ 40 and ~ 50 nm each • Highly enhanced antimicrobial activity against human nosocomial strains • Demonstrated dose dependent toxicity towards osteosarcoma MG-63 cell lines.

  13. Synthesis, interaction with DNA and antiproliferative activities of two novel Cu(II) complexes with Schiff base of benzimidazole

    Science.gov (United States)

    Song, Wen-Ji; Cheng, Jian-Ping; Jiang, Dong-Hua; Guo, Li; Cai, Meng-Fei; Yang, Hu-Bin; Lin, Qiu-Yue

    2014-03-01

    Two novel copper(II) complexes with Schiff base of benzimidazole [Cu(L)Cl]2·CH3OH have been synthesized. HL1 (N-(benzimidazol-2-ymethyl)-5-chlorosalicylideneimine, C15H11ClN3O) and HL2 (N-(benzimidazol-2-ymethyl)-salicylideneimine, C15H12N3O) are ligands of complex (1) and complex (2), respectively. The complexes were characterized by elemental analysis, IR, UV-Vis, TGA and X-ray diffraction. Within the complexes, Cu(II) ions were four coordinated by two nitrogen atom of azomethine and imine, one phenolic oxygen atom from HL and one chloride atom. A distorted quadrilateral structure was formed. Complex (1) crystallized in the triclinic crystal system. Results showed that π-π stacking effect occurred due to the existence of aromatic ring from Schiff base and hydrogen bonding between methanol and adjacent atoms. The DNA binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra and viscosity measurements. Results indicated that complexes bound to DNA via partial intercalation mode. The DNA binding constants Kb/(L mol-1) were 1.81 × 104 (1), 1.37 × 104 (2), 6.27 × 103 (HL1) and 3.14 × 103 (HL2) at 298 K. The title complexes could quench the emission intensities of EB-DNA system significantly. The results of agarose gel electrophoresis indicated complex (1) could cleave supercoiled DNA through the oxidative mechanism. The inhibition ratios revealed that complex (1) and HL1 had strong antiproliferative activities against human breast cancer cells (MCF-7) lines and human colorectal cancer cells (COLO205) lines in vitro. The antiproliferative activities of complex (1) against MCF-7 lines (IC50 = 16.9 ± 1.5 μmol L-1) and against COLO205 lines (IC50 = 16.5 ± 3.4 μmol L-1) is much stronger than that of HL1, which had the potential to develop anti-cancer drug.

  14. Antiproliferative activity of extracts prepared from three species of Reishi on cultured human normal and tumor cell lines.

    Science.gov (United States)

    Katagata, Yohtaro; Sasaki, Fumiyuki

    2010-01-01

    The present study investigated the growth of human fibrosarcoma (HT-1080) and fibroblast (SF-TY) cells in combination with water-soluble (WS) and high molecular component (HMC) fractions prepared from Reishi (R), Rokkaku-Reishi (2R) and Apple Rokkaku-Reishi (A2R). Each WS fraction exhibited dose-and time-dependent inhibition of the growth of the HT-1080 and SF-TY cells. The extracts exhibited marked antiproliferative activity against the HT-1080 cells. The HMC fractions inhibited cell growth dose-and time-dependently in the HT-1080 cells only, and not in the SF-TY cells, suggesting that HMC fractions selectively inhibit HT-1080 cells. Among the HMC fractions, A2R is a strong candidate for anti-tumor targeting since its fraction exhibited better inhibition than the R and 2R fractions. Furthermore, the volume of the A2R fraction was approximately five times greater than that of the others, and included four proteins (molecular mass 9, 13, 22 and 40 kDa) detected by SDS-PAGE. Three of these (13, 22 and 40 kDa) were confirmed to be glycosylated with the Periodic Acid-Schiff Stain kit. These results suggest that A2R may possess anti-tumor activity and, in particular, that the protein components of A2R may act to selectively inhibit the growth of HT-1080 cells.

  15. Cytotoxic Activity and Antiproliferative Effects of Crude Skin Secretion from Physalaemus nattereri (Anura: Leptodactylidae on in vitro Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Andréa Cruz e Carvalho

    2015-10-01

    Full Text Available Anuran secretions are rich sources of bioactive molecules, including antimicrobial and antitumoral compounds. The aims of this study were to investigate the therapeutic potential of Physalaemus nattereri skin secretion against skin cancer cells, and to assess its cytotoxic action mechanisms on the murine melanoma cell line B16F10. Our results demonstrated that the crude secretion reduced the viability of B16F10 cells, causing changes in cell morphology (e.g., round shape and structure shrinkage, reduction in mitochondrial membrane potential, increase in phosphatidylserine exposure, and cell cycle arrest in S-phase. Together, these changes suggest that tumor cells die by apoptosis. This skin secretion was also subjected to chromatographic fractioning using RP-HPLC, and eluted fractions were assayed for antiproliferative and antibacterial activities. Three active fractions showed molecular mass components in a range compatible with peptides. Although the specific mechanisms causing the reduced cell viability and cytotoxicity after the treatment with crude secretion are still unknown, it may be considered that molecules, such as the peptides found in the secretion, are effective against B16F10 tumor cells. Considering the growing need for new anticancer drugs, data presented in this study strongly reinforce the validity of P. nattereri crude secretion as a rich source of new anticancer molecules.

  16. Bark extract mediated green synthesis of silver nanoparticles: Evaluation of antimicrobial activity and antiproliferative response against osteosarcoma.

    Science.gov (United States)

    Nayak, Debasis; Ashe, Sarbani; Rauta, Pradipta Ranjan; Kumari, Manisha; Nayak, Bismita

    2016-01-01

    In the current investigation we report the biosynthesis potentials of bark extracts of Ficus benghalensis and Azadirachta indica for production of silver nanoparticle without use of any external reducing or capping agent. The appearance of dark brown color indicated the complete nanoparticle synthesis which was further validated by absorbance peak by UV-vis spectroscopy. The morphology of the synthesized particles was characterized by Field emission- scanning electron microscopy (Fe-SEM) and atomic force microscopy (AFM). The X-ray diffraction (XRD) patterns clearly illustrated the crystalline phase of the synthesized nanoparticles. ATR-Fourier Transform Infrared (ATR-FTIR) spectroscopy was performed to identify the role of various functional groups in the nanoparticle synthesis. The synthesized nanoparticles showed promising antimicrobial activity against Gram negative (Escherichia coli, Pseudomonas aeruginosa and Vibrio cholerae) and Gram positive (Bacillus subtilis) bacteria. The synthesized nano Ag also showed antiproliferative activity against MG-63 osteosarcoma cell line in a dose dependent manner. Thus, these synthesized Ag nanoparticles can be used as a broad spectrum therapeutic agent against osteosarcoma and microorganisms. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Antiproliferative and antioxidant activity of Aegle marmelos (Linn. leaves in Dalton′s Lymphoma Ascites transplanted mice

    Directory of Open Access Journals (Sweden)

    Vijaya Chockalingam

    2012-01-01

    Full Text Available Objective: The present investigation was performed to evaluate the antiproliferative and antioxidant activity of Aegle marmelos leaves in Dalton′s Lymphoma Ascites (DLA-bearing mice. Materials and Methods: The DLA cells maintained in vivo in Swiss albino mice were used for developing ascitic tumor in mice by intraperitoneal transplantation. The standardized 50% ethanolic extract of A. marmelos leaves (AMEE was administered intraperitoneally in dose levels 200 and 400 mg/kg, after 24 hours of tumor inoculation in mice for two weeks. Results: The AMEE treatment significantly prevented (P<0.001 the increase in body weight due to tumor cell growth and increased the mean survival time of the tumor-bearing mice as compared to the untreated DLA control mice. The treatment of DLA-bearing mice brought down the Alanine Aminotransferase (ALAT, Aspartate Aminotransferase (ASAT, and alkaline phosphatase to normal levels. The extract decreased the levels of hepatic lipid peroxidation and increased the levels of hepatic antioxidants Glutathione, Superoxide Dismutase (SOD, and catalase. All the changes observed with AMEE treatment were dose dependent. Conclusion: The hydroalcoholic extract of A. marmelos exhibits strong antitumor and antioxidant activities in DLA-bearing mice.

  18. A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells.

    Directory of Open Access Journals (Sweden)

    Elena Bausch

    Full Text Available Microtubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and vinca alkaloids have been successfully used in the clinic over the past thirty years against a broad range of tumors. However, two factors have limited the effectiveness of microtubule inhibitors: toxicity and resistance. In particular, the latter is highly unpredictable, variable from patient to patient and is believed to be the cause of treatment failure in most cases of metastatic cancers. For these reasons, there is an increasing demand for new microtubule inhibitors that can overcome resistance mechanisms and that, at the same time, have reduced side effects. Here we present a novel microtubule inhibitor, 4SC-207, which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. In summary, our results suggest that 4SC-207 may be a potential anti-cancer agent.

  19. Purification and characterization of a novel anti-HSV-2 protein with antiproliferative and peroxidase activities from Stellaria media

    Institute of Scientific and Technical Information of China (English)

    Yu Shan; Yuhong Zheng; Fuqin Guan; Jianjian Zhou; Haiguang Zhao; Bing Xia; Xu Feng

    2013-01-01

    A novel antiviral protein,designated as Stellarmedin A,was purified from Stellaria media (L.) Vill.(Caryophyllaceae) by using ammonium sulfate precipitation,cation-exchange chromatography system.Gel electrophoresis analysis showed that Stellarmedin A is a highly basic glycoprotein with a molecular weight of 35.1 kDa and an isoelectric point of ~8.7.The Nterminal 14-amino acid sequence,MGNTGVLTGERNDR,is similar to those of other plant peroxidases.This protein inhibited herpes simplex virus type 2 (HSV-2) replication in vitro with an ICso of 13.18 μg/ml and a therapeutic index exceeding 75.9.It was demonstrated that Stellarmedin A affects the initial stage of HSV-2 infection and is able to inhibit the proliferation of promyelocytic leukemia HL-60 and colon carcinoma LoVo cells with an ICso of 9.09 and 12.32 μM,respectively.Moreover,Stellarmedin A has a peroxidase activity of 36.6 μmol/min/mg protein,when gualacol was used as substrate.To our knowledge,this is the first report about an anti-HSV-2 protein with antiproliferative and peroxidase activities from S.media.

  20. Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

    Science.gov (United States)

    Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog

    2016-01-01

    To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.

  1. Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives.

    Science.gov (United States)

    Zięba, Andrzej; Latocha, Małgorzata; Sochanik, Aleksander; Nycz, Anna; Kuśmierz, Dariusz

    2016-11-04

    A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine) system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines). Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53), apoptosis (BAX, BCL-2), as well as proliferation (H3) were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide.

  2. Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H-quino[3,4-b][1,4]benzothiazine Derivatives

    Directory of Open Access Journals (Sweden)

    Andrzej Zięba

    2016-11-01

    Full Text Available A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines. Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53, apoptosis (BAX, BCL-2, as well as proliferation (H3 were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide.

  3. Antiproliferative Activity of the Methanolic Extract of Withania Somnifera Leaves from Faifa Mountains, Southwest Saudi Arabia, against Several Human Cancer Cell Lines.

    Science.gov (United States)

    Alfaifi, Mohammad Yahya; Saleh, Kamel Ahmed; El-Boushnak, Mohammed Atallah; Elbehairi, Serag Eldin I; Alshehri, Mohammed Ali; Shati, Ali Abdullah

    2016-01-01

    Cancer represent one of the most serious health problems and major causes of death around the world. Many anticancer drugs in clinical use today are natural products or derived from natural sources. Withania somnifera (L.) Dunal is a small shrub widely distributed in many parts of the world including Saudi Arabia. The antiproliferative activities of the methanolic extract of W. somnifera leaves collected from Faifa mountains, southwest Saudi Arabia against MCF-7, HCT116 and HepH2 cell lines were investigated. The extract showed a strong antiproliferative activity against all cell lines with IC50 values of 3.35, 2.19 and 1.89 μg/ml, respectively. Flow cytometry results showed that the extract arrested the cell cycle at S phase, and the increase in the caspase 3 activity suggested that the extract could induce cell apoptosis by a caspase mediated pathway. These results demonstrated that the methanolic extract of W. somnifera leaves collected from Faifa mountains has comparable strong antiproliferative activities to samples collected from different locations.

  4. Promoting moderate-vigorous physical activity in overweight minority girls

    Science.gov (United States)

    There is limited research on the types of activities that are most effective for promoting moderate-vigorous physical activity (MVPA) in children. The purpose of this study was to assess which types of activities elicit MVPA in overweight minority girls. The sample consisted of 31 overweight Latina ...

  5. A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity.

    Science.gov (United States)

    Ude, Ziga; Romero-Canelón, Isolda; Twamley, Brendan; Fitzgerald Hughes, Deirdre; Sadler, Peter J; Marmion, Celine J

    2016-07-01

    7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics.

  6. Design, synthesis and molecular docking of α,β-unsaturated cyclohexanone analogous of curcumin as potent EGFR inhibitors with antiproliferative activity.

    Science.gov (United States)

    Xu, Yun-Yun; Cao, Yi; Ma, Hailkuo; Li, Huan-Qiu; Ao, Gui-Zhen

    2013-01-15

    A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed the most potent EGFR inhibitory activity (IC(50) = 0.43 μM and 1.54 μM, respectively). Molecular docking of I(12) into EGFR TK active site was also performed. This inhibitor nicely fitting the active site might well explain its excellent inhibitory activity.

  7. The calcium channel blocker amlodipine exerts its anti-proliferative action via p21(Waf1/Cip1) gene activation.

    Science.gov (United States)

    Ziesche, Rolf; Petkov, Ventzislav; Lambers, Christopher; Erne, Paul; Block, Lutz-Henning

    2004-10-01

    Proliferation of vascular smooth muscle cells (VSMC) contributes to the progression of atherosclerotic plaques. Calcium channel blockers have been shown to reduce VSMC proliferation, but the underlying molecular mechanism remains unclear. p21(Waf1/Cip1) is a potent inhibitor of cell cycle progression. Here, we demonstrate that amlodipine (10(-6) to 10(-8) M) activates de novo synthesis of p21(Waf1/Cip1) in vitro. We show that amlodipine-dependent activation of p21(Waf1/Cip1) involves the action of the glucocorticoid receptor (GR) and C/EBP-alpha. The underlying pathway apparently involves the action of mitogen-activated protein kinase or protein kinase C, but not of extracellular signal-related kinase or changes of intracellular calcium. Amlodipine-induced p21(Waf1/Cip1) promoter activity and expression were abrogated by C/EBP-alpha antisense oligonucleotide or by the GR antagonist RU486. Amlodipine-dependent inhibition of cell proliferation was partially reversed by RU486 at 10(-8) M (58%+/-29%), antisense oligonucleotides targeting C/EBP-alpha (91%+/-26%), or antisense mRNAs targeting p21(Waf1/Cip1) (96%+/-32%, n=6); scrambled antisense oligonucleotides or those directed against C/EBP-beta were ineffective. The data suggest that the anti-proliferative action of amlodipine is achieved by induction of the p21 (Waf1/Cip1) gene, which may explain beneficial covert effects of this widely used cardiovascular therapeutic drug beyond a more limited role as a vascular relaxant.

  8. Effects of nanoparticles with hydrotropic nicotinamide on tacrolimus: permeability through psoriatic skin and antipsoriatic and antiproliferative activities.

    Science.gov (United States)

    Wan, Tao; Pan, Wenhui; Long, Yueming; Yu, Kaiyue; Liu, Sibo; Ruan, Wenyi; Pan, Jingtong; Qin, Mengyao; Wu, Chuanbin; Xu, Yuehong

    2017-01-01

    The hybrid system based on nanoparticles (NPs) self-assembled by the conjugations of hyaluronic acid with cholesterol (HA-Chol NPs) combined with nicotinamide (NIC) for tacrolimus (FK506), ie, FK506 NPs-NIC, has been confirmed to exhibit a significant synergistic effect on FK506 permeation through and into intact skin; thus, it may be a promising approach for FK506 to effectively treat skin diseases. The aim of this study was to evaluate its potential for the treatment of psoriasis. In vitro permeation through the psoriatic skin was carried out, and the results revealed that the combination of NPs with NIC exhibited a significant synergistic effect on FK506 deposition within the psoriatic skin (3.40±0.67 μg/cm(2)) and penetration through the psoriatic skin (30.86±9.66 μg/cm(2)). The antipsoriatic activity of FK506 NPs-NIC was evaluated through the treatment for imiquimod (IMQ)-induced psoriasis. The psoriasis area and severity index (PASI) score demonstrated that FK506 HA-Chol NPs-NIC exerted the effect on ameliorating the skin lesions comparable to clobetasol propionate (a positive drug for psoriasis) and superior to commercial FK506 ointment (Protopic(®)), and the histological study showed that it presented a synergistic effect on antipsoriasis after FK506 incorporation into NPs combined with NIC hydrotropic system, which might ultimately increase the therapeutic effect and minimize the systemic side effects by reducing the overall dose of FK506. RAW 264.7 cell uptake presented the enhancement of drugs delivered into cells by HA-Chol NPs-NIC. The antiproliferative activity on HaCaT cells identified that FK506 HA-Chol NPs-NIC exhibited significant inhibiting effects on HaCaT proliferation. The results support that the combination of HA-Chol NPs with NIC is a promising approach for FK506 for the treatment of psoriasis.

  9. Effects of nanoparticles with hydrotropic nicotinamide on tacrolimus: permeability through psoriatic skin and antipsoriatic and antiproliferative activities

    Science.gov (United States)

    Wan, Tao; Pan, Wenhui; Long, Yueming; Yu, Kaiyue; Liu, Sibo; Ruan, Wenyi; Pan, Jingtong; Qin, Mengyao; Wu, Chuanbin; Xu, Yuehong

    2017-01-01

    The hybrid system based on nanoparticles (NPs) self-assembled by the conjugations of hyaluronic acid with cholesterol (HA–Chol NPs) combined with nicotinamide (NIC) for tacrolimus (FK506), ie, FK506 NPs–NIC, has been confirmed to exhibit a significant synergistic effect on FK506 permeation through and into intact skin; thus, it may be a promising approach for FK506 to effectively treat skin diseases. The aim of this study was to evaluate its potential for the treatment of psoriasis. In vitro permeation through the psoriatic skin was carried out, and the results revealed that the combination of NPs with NIC exhibited a significant synergistic effect on FK506 deposition within the psoriatic skin (3.40±0.67 μg/cm2) and penetration through the psoriatic skin (30.86±9.66 μg/cm2). The antipsoriatic activity of FK506 NPs–NIC was evaluated through the treatment for imiquimod (IMQ)-induced psoriasis. The psoriasis area and severity index (PASI) score demonstrated that FK506 HA–Chol NPs–NIC exerted the effect on ameliorating the skin lesions comparable to clobetasol propionate (a positive drug for psoriasis) and superior to commercial FK506 ointment (Protopic®), and the histological study showed that it presented a synergistic effect on antipsoriasis after FK506 incorporation into NPs combined with NIC hydrotropic system, which might ultimately increase the therapeutic effect and minimize the systemic side effects by reducing the overall dose of FK506. RAW 264.7 cell uptake presented the enhancement of drugs delivered into cells by HA–Chol NPs–NIC. The antiproliferative activity on HaCaT cells identified that FK506 HA–Chol NPs–NIC exhibited significant inhibiting effects on HaCaT proliferation. The results support that the combination of HA–Chol NPs with NIC is a promising approach for FK506 for the treatment of psoriasis.

  10. Synthesis of substituted 3-amino-N-phenyl-1H-indazole-1-carboxamides endowed with antiproliferative activity.

    Science.gov (United States)

    Maggio, Benedetta; Raimondi, Maria Valeria; Raffa, Demetrio; Plescia, Fabiana; Cascioferro, Stella; Plescia, Salvatore; Tolomeo, Manlio; Di Cristina, Antonietta; Pipitone, Rosaria Maria; Grimaudo, Stefania; Daidone, Giuseppe

    2011-01-01

    Several new N-phenyl-1H-indazole-1-carboxamides 1c-h and 4l,m were prepared by reacting phenyl isocyanate derivatives 3a,b with 3-amino-1H-indazole derivatives 2c,e,g or 1H-indazole 2l respectively. Chemical transformations of compounds 1a,b and 1g,h gave 3-acetamido-N-phenyl-1H-indazole-1-carboxamide derivatives 5a,b, and 3,5-diamino-N-phenyl-1H-indazole-1-carboxamide derivatives 4i,j respectively. Finally, 3,5-diacetamido-N-phenyl-1H-indazole-1-carboxamide derivatives 6a,b were prepared by acetylation of 4i,j. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell lines panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). Compound 1c, the most active of the series, was able to inhibit cell growth showing GI(50) values in the 0.041-33.6 μM range, mean GI(50) 1.90 μM, being very effective against colon and melanoma cell lines. Cell cycle analysis in K562 cells showed that 1c causes a marked increase of cells in G0-G1 phase. Moreover, it increases the ratio between hypophosphorylated pRb and total pRb.

  11. Synthesis of indazole based diarylurea derivatives and their antiproliferative activity against tumor cell lines.

    Science.gov (United States)

    Zhao, Cui-rong; Wang, Rui-qi; Li, Gang; Xue, Xiao-xia; Sun, Chang-jun; Qu, Xian-jun; Li, Wen-bao

    2013-04-01

    New series of indazole based diarylureas were synthesized and their anticancer activity against cancer cells H460, A549, OS-RC-2, HT-29, Lovo, HepG2, Bel-7402, SGC-7901 and MDA-MB-231 were examined. These derivatives of diarylureas, except azaindazole based diarylureas 5f, 5l and 5m, showed superior or similar activity against most of these selected cancer cell lines to the reference compound sorafenib. The effect of substituents on the indazole ring was also investigated. Derivatives with trifluoromenthy or halogen substituent on the indazole ring showed higher activity against the selected cancer cell lines than sorafenib. The acute toxicity assay showed that compounds 5a, 5b and 5i possessed lower toxicity than sorafenib. Compound 5i with 4-(trifluoromenthy)-1H-indazole and 4-(trifluoromenthy) benzene moieties exhibited the most potent anticancer activity.

  12. Antioxidant capacity of food mixtures is not correlated with their antiproliferative activity against MCF-7 breast cancer cells.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan; Meckling, Kelly A; Marcone, Massimo F

    2013-12-01

    Combining different foods may produce additive, synergistic, or antagonistic interactions that may modify certain physiological effects (i.e., anticancer properties). For investigating these interactions and potential synergetic combinations, thirteen foods from three categories, including fruits (raspberries, blackberries, apples, grapes), vegetables (broccoli, tomatoes, mushrooms, purple cauliflowers, onions), and legumes (soy beans, adzuki beans, red kidney beans, black beans), were evaluated for their inhibitory activity against MCF-7 breast cancer cells. Grape, onion, and adzuki bean showed maximal growth inhibition of MCF-7 from the fruit, vegetable, and legume groups, respectively. When these three foods were combined in pairs, unique interactions were observed that were not seen when individual extracts were used. Combining onion and grape resulted in a synergistic antiproliferative effect (APE) against MCF-7 compared with either onion or grape treatment alone. In contrast, combining grape and adzuki bean resulted in an antagonistic interaction. Additionally, four antioxidant assays (total phenolic contents, ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl, and oxygen radical absorbance capacity) were further used to evaluate the antioxidant capacities (AC) of individual foods and their combinations. Combining raspberry and adzuki bean extracts demonstrated synergistic AC in all four assays, but they did not show synergistic APE against the MCF-7 cells. Combining broccoli and soy produced antioxidant antagonism, but did not have an antagonistic APE against MCF-7. The synergistic or antagonistic AC of food mixtures did not correlate with the synergistic or antagonistic APE against MCF-7. Further investigation is to determine the mechanisms of these interactions and to predict and enhance the therapeutic benefits of foods and food components through strategic food combinations.

  13. Design of antitumor agents containing carbohydrate based on GLUT1, and evaluation of antiproliferative activity.

    Science.gov (United States)

    Zhang, Renshuai; Song, Lairong; Jiang, Bo; Wang, Lijun; Wu, Ning; Guo, Shuju; Shi, Dayong

    2017-06-01

    A series of novel carbohydrate-modified antitumor compounds were designed based on glucose transporter 1 (GLUT1), and evaluated for their anticancer activities against four cancer cell lines. The ribose derivatives (compound 9 and 10) exhibited modest inhibitory activity. The compound 9 significantly inhibited the migration of A549 cell and induced A549 cell apoptosis in a concentration-dependent manner. Moreover, compound 9 blocked A549 cells at the G0/G1 phase. The cellular uptake studies suggested that ribose-modified compound 9 could be taken through GLUT1 in A549 cell line. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Isolation and characterization of a novel lectin with antifungal and antiproliferative activities from Sophora alopecuroides seeds

    Institute of Scientific and Technical Information of China (English)

    Tinging Li; Xiaoli Yin; Dongliang Liu; Xiaojin Ma; Hui Lv; Surong Sun

    2012-01-01

    Sophora alopecuroides lectin (SAL),a novel lectin from the seeds of Sophora alopecuroides,was purified by ionexchange chromatography on diethylaminoethyl (DEAE)-and carboxymethyl (CM)-Sepharose columns,followed by gel filtration on a Sephadex 75 10/300 GL column.SAL was found to be a monomer of 39916.3 Da,as determined by tricine-sodium dodecyl sulphate-polyacrylamide gel electrophoresis and high-performance liquid chromato-graphy (HPLC).The N-terminal 10-amino acid sequence of SAL,KPWALSFSFG,resembles those of other legume lectins.SAL exhibits hemagglutinating activity against rabbit erythrocytes at 11.9 μg/ml.Its hemagglutinating activity is stable in the pH range 7-11 and in the temperature range 30-90℃,and is stimulated by Mn2+.The hemagglutinating activity of SAL is most potently inhibited by 50-mM D-galactose.SAL suppresses mycelial growth in Penicillium digitatum and Alternaria alternata;the IC50 of the antifungal activity toward P.digitatum and A.alternata were found to be 3.125 and 3.338 μM,respectively.SAL suppresses the proliferation of human cervical cancer cells (HeLa) at an ICso of 6.25 μM (P< 0.05).But it has no inhibiting effect on bacteria.This is the first report of a lectin from seeds of S.alopecuroides.

  15. SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper (II) complex.

    Science.gov (United States)

    Weintraub, Sagiv; Moskovitz, Yoni; Fleker, Ohad; Levy, Ariel R; Meir, Aviv; Ruthstein, Sharon; Benisvy, Laurent; Gruzman, Arie

    2015-12-01

    The search for novel anticancer therapeutic agents is an urgent and important issue in medicinal chemistry. Here, we report on the biological activity of the copper-based bioinorganic complex Cu4 (2,4-di-tert-butyl-6-(1H-imidazo- [1, 10] phenanthrolin-2-yl)phenol)4]·10 CH3CN (2), which was tested in rat L6 myotubes, mouse NSC-34 motor neurone-like cells, and HepG-2 human liver carcinoma. Upon 96 h incubation, 2 exhibited a significant cytotoxic effect on all three types of cells via activation of two cell death mechanisms (apoptosis and necrosis). Complex 2 exhibited better potency and efficacy than the canonical cytotoxic drug cisplatin. Moreover, during shorter incubations, complex 2 demonstrated a significant SOD mimetic activity, and it was more effective and more potent than the well-known SOD mimetic TEMPOL. In addition, complex 2 was able to interact with DNA and, cleave DNA in the presence of sodium ascorbate. This study shows the potential of using polynuclear redox active compounds for developing novel anticancer drugs through SOD-mimetic redox pathways.

  16. A novel ribonuclease with antiproliferative activity from fresh fruiting bodies of the edible mushroom Hypsizigus marmoreus.

    Science.gov (United States)

    Guan, G P; Wang, H X; Ng, T B

    2007-12-01

    An 18-kDa ribonuclease (RNase) with a novel N-terminal sequence was purified from fresh fruiting bodies of the mushroom Hypsizigus marmoreus. The purification protocol comprised ion exchange chromatography on DEAE cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose and Q-Sepharose and gel filtration by fast protein liquid chromatography on Superdex 75. The starting buffer was 10 mM Tris-HCl buffer (pH 7.2), 10 mM Tris-HCl buffer (pH 7.2), 10 mM NH(4)OAc buffer (pH 5), 10 mM NH(4)HCO(3) buffer (pH 9.4) and 200 mM NH(4)HCO(3) (pH 8.5), respectively. Absorbed proteins were desorbed using NaCl added to the starting buffer. A 42-fold purification of the enzyme was achieved. The RNase was unadsorbed on DEAE cellulose, Affi-gel blue gel and CM-cellulose but adsorbed on Q-Sepharose. It exhibited maximal RNase activity at pH 5 and 70 degrees C. Some RNase activity was detectable at 100 degrees C. It demonstrated the highest ribonucleolytic activity (196 U/mg) toward poly C, the next highest activity (126 U/mg) toward poly A, and much weaker activity toward poly U (48 U/mg) and poly G (41 U/mg). The RNase inhibited [(3)H-methyl]-thymidine uptake by leukemia L1210 cells with an IC(50) of 60 microM.

  17. Potential Moderators of Physical Activity on Brain Health

    Directory of Open Access Journals (Sweden)

    Regina L. Leckie

    2012-01-01

    Full Text Available Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE, brain derived neurotrophic factor (BDNF, and catechol-O-methyltransferase (COMT along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA, as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function.

  18. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer

    Directory of Open Access Journals (Sweden)

    Can Liu

    2016-06-01

    Full Text Available Colorectal cancer and throat cancer are the world’s most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9 and phosphorylated extracellular signal-regulated kinases (ERK1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

  19. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer.

    Science.gov (United States)

    Liu, Can; Dai, Longhai; Liu, Yueping; Rong, Long; Dou, Dequan; Sun, Yuanxia; Ma, Lanqing

    2016-06-13

    Colorectal cancer and throat cancer are the world's most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9) and phosphorylated extracellular signal-regulated kinases (ERK)1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

  20. SYNTHESIS AND IN VITRO ANTIPROLIFERATIVE ACTIVITY OF NOVEL 2-ARYLIDENEAMINOBENZIMIDAZOLE DERIVATIVES.

    Science.gov (United States)

    Nowicka, Anna; Liszkiewicz, Hanna; Nawrocka, Wanda P; Wietrzyk, Joanna; Sadowska, Joanna

    2015-01-01

    A new class of Mannich bases 9-26, derivatives of 2-amino-1H-benzimidazole, were obtained in the condensation of Schiff bases 1-4 or 2-benzylaminobenzimidazoles 5-8 with selected secondary amines: morpholine, piperidine, N-methylpiperazine, N-phenylpiperazine, 1-(2-pyridyl)piperazine, 1(2-methoxyphenyl)piperazine, 1-(2-pyrimidinyl)piperazine and formaldehyde in ethanol. The pyrimido[1,2-albenzimidazole derivatives 27-29 have been synthesized in the reactions of Schiff base 2 with selected compounds containing active methylene group: acetylacetone, benzoylacetone and malononitrile. The structures 1-29 were confirmed by the results of elementary analysis and their IR, 1H- and 13C-NMR spectra. The products 1-29 are of interest for biological studies and can be substrates for further synthesis. All compounds were screened against the cells of MV4-11 human leukemia and then the most active of them 5, 7, 9-16, 24-26, 28, 29 were tested towards human T47D breast and A549 lung cancer cells as well as normal mouse fibroblasts (BALB/3T3). The most active compound against the cancer cell lines was 4-amino-3-cyano-2-(4-hydroxyphenylene)-1,2-dihydropyrimi-do[1,2-a]benzimidazole (29) (IC50 0.23 ± 0.05 µg/mL against MV4-11 cells) showing in parallel very low cytotoxicity towards mouse fibroblasts. Cisplatin was the control drug.

  1. Cooperative antiproliferative and differentiation-enhancing activity of medicinal plant extracts in acute myeloid leukemia cells.

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    Zhamanbayeva, Gulzhan T; Aralbayeva, Araylim N; Murzakhmetova, Maira K; Tuleukhanov, Sultan T; Danilenko, Michael

    2016-08-01

    Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with poor prognosis and limited treatment options. Sea buckthorn (Hippophae rhamnoides) berries, dog rose (Rosa canina) rosehips, and garden sage (Salvia officinalis) and oregano (Origanum vulgare) aerial parts are widely used in traditional medicine and exhibit antitumor effects in preclinical models. However, these plants remain scarcely tested for antileukemic activity. Here, we show that their water-ethanol leaf extracts reduced the growth and viability of AML cells and, at non-cytotoxic doses, potentiated cell differentiation induced by a low concentration of 1α,25-dihydroxyvitamin D3, the hormonal form of vitamin D, in a cell type-dependent manner. The latter effect was accompanied by upregulation of the vitamin D receptor protein components and its transcriptional activity. Furthermore, at minimally effective doses the extracts cooperated with one another to produce marked cytostatic effects associated with a partial S-phase arrest and a modest induction of apoptosis. In contrast, these combinations only slightly affected the growth and viability of proliferating normal human peripheral blood mononuclear cells. In addition, the extracts strongly inhibited microsomal lipid peroxidation and protected normal erythrocytes against hypoosmotic shock. Our results suggest that further exploration of the enhanced antileukemic effects of the combinations tested here may lead to the development of alternative therapeutic and preventive approaches against AML. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. The effect of five Taraxacum species on in vitro and in vivo antioxidant and antiproliferative activity.

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    Mingarro, D Muñoz; Plaza, A; Galán, A; Vicente, J A; Martínez, M P; Acero, N

    2015-08-01

    Plants belonging to the genus Taraxacum are considered a nutritious food, being consumed raw or cooked. Additionally, these plants have long been used in folk medicine due to their choleretic, diuretic, antitumor, antioxidant, antiinflammatory, and hepatoprotective properties. This genus, with its complex taxonomy, includes several species that are difficult to distinguish. Its traditional use must be related not only to T. officinale F.H. Wigg., the most studied species, but also to others. The aim of this work is to compare five different common South European species of Taraxacum (T. obovatum (Willd.) DC., T. marginellum H. Lindb., T. hispanicum H. Lindb., T. lambinonii Soest and T. lacistrum Sahlin), in order to find differences between antioxidant and cytotoxic activities among them. Dissimilarities between species in LC/MS patterns, in in vitro and intracellular antioxidant activity and also in the cytotoxicity assay were found. T. marginellum was the most efficient extract reducing intracellular ROS levels although in in vitro assays, T. obovatum was the best free radical scavenger. A relevant cytotoxic effect was found in T. lacistrum extract over HeLa and HepG2 cell lines.

  3. Antiproliferative activities of Amaryllidaceae alkaloids from Lycoris radiata targeting DNA topoisomerase I

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    Chen, Gui-Lin; Tian, Yong-Qiang; Wu, Jian-Lin; Li, Na; Guo, Ming-Quan

    2016-01-01

    Crude Amaryllidaceae alkaloids (AAs) extracted from Lycoris radiata are reported to exhibit significant anti-cancer activity. However, the specific alkaloids responsible for the pharmacodynamic activity and their targets still remain elusive. In this context, we strived to combine affinity ultrafiltration with topoisomerase I (Top I) as a target enzyme aiming to fish out specific bioactive AAs from Lycoris radiata. 11 AAs from Lycoris radiata were thus screened out, among which hippeastrine (peak 5) with the highest Enrichment factor (EF) against Top I exhibited good dose-dependent inhibition with IC50 at 7.25 ± 0.20 μg/mL comparable to camptothecin (positive control) at 6.72 ± 0.23 μg/mL. The molecular docking simulation further indicated the inhibitory mechanism between Top I and hippeastrine. The in vitro antiproliferation assays finally revealed that hippeastrine strongly inhibited the proliferation of HT-29 and Hep G2 cells in an intuitive dose-dependent manner with the IC50 values at 3.98 ± 0.29 μg/mL and 11.85 ± 0.20 μg/mL, respectively, and also induced significant cellular morphological changes, which further validated our screening method and the potent antineoplastic effects. Collectively, these results suggested that hippeastrine could be a very promising anticancer candidate for the therapy of cancer in the near future. PMID:27922057

  4. Individuals underestimate moderate and vigorous intensity physical activity.

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    Karissa L Canning

    Full Text Available BACKGROUND: It is unclear whether the common physical activity (PA intensity descriptors used in PA guidelines worldwide align with the associated percent heart rate maximum method used for prescribing relative PA intensities consistently between sexes, ethnicities, age categories and across body mass index (BMI classifications. OBJECTIVES: The objectives of this study were to determine whether individuals properly select light, moderate and vigorous intensity PA using the intensity descriptions in PA guidelines and determine if there are differences in estimation across sex, ethnicity, age and BMI classifications. METHODS: 129 adults were instructed to walk/jog at a "light," "moderate" and "vigorous effort" in a randomized order. The PA intensities were categorized as being below, at or above the following %HRmax ranges of: 50-63% for light, 64-76% for moderate and 77-93% for vigorous effort. RESULTS: On average, people correctly estimated light effort as 51.5±8.3%HRmax but underestimated moderate effort as 58.7±10.7%HRmax and vigorous effort as 69.9±11.9%HRmax. Participants walked at a light intensity (57.4±10.5%HRmax when asked to walk at a pace that provided health benefits, wherein 52% of participants walked at a light effort pace, 19% walked at a moderate effort and 5% walked at a vigorous effort pace. These results did not differ by sex, ethnicity or BMI class. However, younger adults underestimated moderate and vigorous intensity more so than middle-aged adults (P<0.05. CONCLUSION: When the common PA guideline descriptors were aligned with the associated %HRmax ranges, the majority of participants underestimated the intensity of PA that is needed to obtain health benefits. Thus, new subjective descriptions for moderate and vigorous intensity may be warranted to aid individuals in correctly interpreting PA intensities.

  5. Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells

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    Hire, Rupali R.; Srivastava, Shalini; Davis, Melissa B.; Kumar Konreddy, Ananda; Panda, Dulal

    2017-01-01

    Crocin, a component of saffron spice, is known to have an anticancer activity. However, the targets of crocin are not known. In this study, crocin was found to inhibit the proliferation of HCC70, HCC1806, HeLa and CCD1059sk cells by targeting microtubules. Crocin depolymerized both the interphase and mitotic microtubules of different cancer cells, inhibited mitosis and induced multipolar spindle formation in these cells. In vitro, crocin inhibited the assembly of pure tubulin as well as the assembly of microtubule-associated protein rich tubulin. Electron microscopic analysis showed that crocin inhibited microtubule assembly while it induced aggregation of tubulin at higher concentrations. Crocin co-eluted with tubulin suggesting that it binds to tubulin. Vinblastine inhibited the binding of crocin to tubulin while podophyllotoxin did not inhibit the crocin binding indicating that crocin binds at the vinblastine site on tubulin. The results suggested that crocin inhibited cell proliferation mainly by disrupting the microtubule network. PMID:28337976

  6. Differentiation-inducing and anti-proliferative activities of lupeol on canine melanoma cells.

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    Ogihara, Kikumi; Naya, Yuko; Okamoto, Yoshiharu; Hata, Keishi

    2014-01-01

    Canine melanoma is the most common oral malignant tumor reported in the field of veterinary medicine. We found that lupeol, a lupine triterpene, inhibited mouse melanoma cell growth in vitro and in vivo by inducing cell differentiation. In the present study, we examined the differentiation-inducing activities of lupeol on 4 canine melanoma cells in vitro and in vivo. The induction of canine melanoma cell differentiation by lupeol was confirmed by evaluating some differentiation markers such as tyrosinase with real-time RT-PCR. Furthermore, we transplanted canine melanoma cells into a severe combined immunodeficiency mouse, and studied the anti-progressive effects of lupeol on tumor tissue. The gene expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-2, which are markers of pigment cell differentiation, was induced in 4 canine oral malignant melanoma cells by lupeol, and the agent markedly inhibited tumor progression in canine melanoma-bearing mice.

  7. Antibacterial and Antiproliferative Activities of Plumericin, an Iridoid Isolated from Momordica charantia Vine

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    Jutamas Saengsai

    2015-01-01

    Full Text Available Plumericin, an iridoid lactone, was isolated with relatively high yield from Momordica charantia vine using the supercritical fluid extraction (SFE and the separation box (Sepbox comprising dual combination of high-performance liquid chromatography and solid phase extraction. This compound showed antibacterial activity against Enterococcus faecalis and Bacillus subtilis with minimum inhibitory concentration (MIC values better than cloxacillin. Plumericin potently inhibited proliferation of two leukemic cancer cell lines: they were acute and chronic leukemic cancer cell lines, NB4 and K562, with the effective doses (ED50 of 4.35 ± 0.21 and 5.58 ± 0.35 μg/mL, respectively. In addition, the mechanism of growth inhibition in both cell lines was induced by apoptosis, together with G2/M arrest in K562 cells.

  8. Apoptosis-mediated antiproliferative activity of friedolanostane triterpenoid isolated from the leaves of Garcinia celebica against MCF-7 human breast cancer cell lines

    Science.gov (United States)

    SUBARNAS, ANAS; DIANTINI, AJENG; ABDULAH, RIZKY; ZUHROTUN, ADE; NUGRAHA, PATRIA A.; HADISAPUTRI, YUNI E.; PUSPITASARI, IRMA M.; YAMAZAKI, CHIHO; KUWANO, HIROYUKI; KOYAMA, HIROSHI

    2016-01-01

    The leaves of Garcinia celebica strongly inhibit the proliferation of MCF-7 human breast adenocarcinoma cell lines. The present study focused on investigating the active anticancer and antiproliferative compound from the G. celebica leaves and assessing its mechanism of action. Ethanol extracts of G. celebica were fractionated based on their polarity using n-hexane, ethyl acetate and water. The antiproliferative properties were tested in vitro against MCF-7 human breast cancer cell lines using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. The active compound was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested for its antiproliferative properties and the mechanism by which it induces apoptosis in MCF-7 cells by western blot analysis of the activated apoptotic proteins. This resulted in the isolation of a friedolanostane triterpenoid, which was determined to be methyl-3α, 23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat. This compound inhibited MCF-7 cell proliferation in a time- and dose-dependent manner with IC50 values of 82 and 70 µM for the 24 and 48 h treatments, respectively. Furthermore, the western blot analysis suggested that the compound exerted its anticancer activities by promoting apoptosis through the inhibition of the oncogenic protein Akt, thereby increasing the expression of poly (ADP-ribose) polymerase (PARP) protein. These results suggest that methyl-3α,23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat is the anticancer compound found in G. celebica, providing a basis for its potential use in cancer disease management. PMID:26870339

  9. New Acetylenic Amine Derivatives of 5,8-Quinolinediones: Synthesis, Crystal Structure and Antiproliferative Activity

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    Monika Kadela-Tomanek

    2017-01-01

    Full Text Available Acetylenic amine derivatives of the 5,8-quinolinedione were synthesized and characterized by the 1H and 13C NMR, IR spectroscopy and MS spectra. Additionally, the 6- and 7-substituted allylamine-5,8-quinolinediones were synthesized for comparison purposes. The crystal structure was determined for the 6-chloro-7-propargylamine-5,8-quinolinedione and 7-chloro-6-propargylamine-5,8-quinolinedione. Additionally, the IR spectral analysis supplemented by the density functional theory (DFT calculations were carried out. It was found that different positions of the propargylamine side chain had a distinct influence on crystal structure, formation of H-bonds and the carbonyl stretching IR bands. Correlation between the frequency separation Δν of the carbonyl IR bands and the position of the 6- and 7-substituents was found. The 7-substituted derivatives exhibited a higher frequency separation Δν. The observed correlation could provide an opportunity to use the IR spectroscopy to study substitution reactions. Cytotoxic activities against three human cancer cell lines for the 5,8-quinolinedione derivatives with different amine substituents, i.e., propargylamine, N-methylpropargylamine, 1,1-dimethylpropargylamine, allylamine and propylamine were also analysed with respect to their molecular structure.

  10. An antifungal peptide with antiproliferative activity toward tumor cells from red kidney beans.

    Science.gov (United States)

    Li, Miao; Wang, Hexiang; Ng, Tzi Bun

    2011-06-01

    A 7.3-kDa antifungal peptide was purified from dried red kidney beans. The purification procedure entailed ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose, followed by fast protein liquid chromatography-gel filtration on Superdex 75. The peptide was unadsorbed on DEAE-cellulose but adsorbed on Affi-gel blue gel and CM-cellulose. It exhibited a molecular mass of 7.3 kDa in gel filtration and also in SDS-polyacrylamide gel electrophoresis, indicating that it is a single-chained protein. The N-terminal sequence of the peptide was DGVCFGGLANGDRT. The peptide exerted an antifungal action on Fusarium oxysporum with an IC₅₀ of 3.8±0.4 µM (mean±SD, n=3). It also inhibited mycelial growth in Mycosphaerella arachidicola. It suppressed growth of lymphoma MBL2 cells and leukemia L1210 cells with an IC₅₀ of 5.2±0.4 µM and 7.6±0.6 µM, respectively. HIV-1 reverse transcriptase was inhibited with an IC₅₀ of 40±3.2 µM. However, no activity was demonstrated toward other viral enzymes.

  11. Chalcone derivatives from the fern Cyclosorus parasiticus and their anti-proliferative activity.

    Science.gov (United States)

    Wei, Han; Zhang, Xuenong; Wu, Guanghua; Yang, Xian; Pan, Songwei; Wang, Yanyan; Ruan, Jinlan

    2013-10-01

    Three new chalcone derivatives, named parasiticins A-C (1-3), were isolated from the leaves of Cyclosorus parasiticus, together with four known chalcones, 5,7-dihydroxy-4-phenyl-8-(3-phenyl-trans-acryloyl)-3,4-dihydro-1-benzopyran-2-one (4), 2'-hydroxy-4',6'-dimethoxychalcone (5), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (6), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (7). The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of compounds 1-7 were evaluated against six human cancer cell lines in vitro. Compounds 3 and 6 exhibited substantial cytotoxicity against all six cell lines, especially toward HepG2 with the IC₅₀ values of 1.60 and 2.82 μM, respectively. Furthermore, we demonstrated that compounds 3 and 6 could induce apoptosis in the HepG2 cell line, which may contribute significantly to their cytotoxicity.

  12. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

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    De Maria Ruggero

    2008-07-01

    Full Text Available Abstract Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w had a mean size Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.

  13. Design, synthesis and in vitro antiproliferative activity of novel isatin-quinazoline hybrids.

    Science.gov (United States)

    Fares, Mohamed; Eldehna, Wagdy M; Abou-Seri, Sahar M; Abdel-Aziz, Hatem A; Aly, Mohamed H; Tolba, Mai F

    2015-02-01

    Using a molecular hybridization approach, a new series of isatin-quinazoline hybrids 15a-o was designed and synthesized via two different synthetic routes. The target compounds 15a-o were prepared by the reaction of quinazoline hydrazines 12a-e with indoline-2,3-diones 13a-c or by treating 4-chloroquinazoline derivatives 11a-e with isatin hydrazones 14a-c. The in vitro anticancer activity of the newly synthesized hybrids was evaluated against the liver HepG2, breast MCF-7 and colon HT-29 cancer cell lines. A distinctive selective growth inhibitory effect was observed towards the HepG2 cancer cell line. Compounds 15b, 15g and 15l displayed the highest potency, with IC50 values ranging from 1.0 ± 0.2 to 2.4 ± 0.4 μM, and they were able to induce apoptosis in HepG2 cells, as evidenced by enhanced expression of the pro-apoptotic protein Bax and reduced expression of the anti-apoptotic protein Bcl-2, in addition to increased caspase-3 levels.

  14. Anticancer activity of five forest crops used in African folklore: antiproliferative and pro-apoptotic effects.

    Science.gov (United States)

    Erharuyi, Osayemwenre; Engel-Lutz, Nadja; Ahomafor, Joy; Imieje, Vincent; Falodun, Abiodun; Nebe, Babara; Langer, Peter

    2014-02-26

    Acalypha wilkesiana, Caesalpinia bonduc, Jatropha multifida, Momordica charantia and Picralima nitida used in African folklore for treating cancer were investigated. All extracts except J. multifida resulted in no significant alteration in cell cycle distribution and apoptosis in MCF-7 and BT-20. The J. multifilda (JMR-Ch) caused cell cycle arrest at G1 checkpoint and apoptosis in MCF-7. Slight changes in the integrin expression of MCF-7 after treatment with 1 and 10 μg/mL of JMR-Ch were observed. Fluorescence-activated confocal microscopy shows changes in cell morphology and β1 integrin localisation within MCF-7 cells after exposure to 10 and 25 μg/mL of JMR-Ch. JMR-Ch (1 μg/mL) treatment resulted in time-dependent decrease in cell acidification and respiration in MCF-7 cells and a time-dependent decrease in BT-20 cell respiration, while in MCF-10A, there was an enhancement of acidification. These results revealed the probable application of JMR-Ch in cancer therapy.

  15. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

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    Hussein MZ

    2011-07-01

    Full Text Available Mohd Zobir Hussein1,2, Samer Hasan Al Ali2, Zulkarnain Zainal2, Muhammad Nazrul Hakim31Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology (ITMA, 2Department of Chemistry, Faculty of Science, 3Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: An ellagic acid (EA–zinc layered hydroxide (ZLH nanohybrid (EAN was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8′ position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host–guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA.Keywords: ellagic acid, nonaqueous solution, ZnO, zinc-layered hydroxide, viability test

  16. Effects of nanoparticles with hydrotropic nicotinamide on tacrolimus: permeability through psoriatic skin and antipsoriatic and antiproliferative activities

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    Wan T

    2017-02-01

    Full Text Available Tao Wan,* Wenhui Pan,* Yueming Long, Kaiyue Yu, Sibo Liu, Wenyi Ruan, Jingtong Pan, Mengyao Qin, Chuanbin Wu, Yuehong Xu Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The hybrid system based on nanoparticles (NPs self-assembled by the conjugations of hyaluronic acid with cholesterol (HA–Chol NPs combined with nicotinamide (NIC for tacrolimus (FK506, ie, FK506 NPs–NIC, has been confirmed to exhibit a significant synergistic effect on FK506 permeation through and into intact skin; thus, it may be a promising approach for FK506 to effectively treat skin diseases. The aim of this study was to evaluate its potential for the treatment of psoriasis. In vitro permeation through the psoriatic skin was carried out, and the results revealed that the combination of NPs with NIC exhibited a significant synergistic effect on FK506 deposition within the psoriatic skin (3.40±0.67 µg/cm2 and penetration through the psoriatic skin (30.86±9.66 µg/cm2. The antipsoriatic activity of FK506 NPs–NIC was evaluated through the treatment for imiquimod (IMQ-induced psoriasis. The psoriasis area and severity index (PASI score demonstrated that FK506 HA–Chol NPs–NIC exerted the effect on ameliorating the skin lesions comparable to clobetasol propionate (a positive drug for psoriasis and superior to commercial FK506 ointment (Protopic®, and the histological study showed that it presented a synergistic effect on antipsoriasis after FK506 incorporation into NPs combined with NIC hydrotropic system, which might ultimately increase the therapeutic effect and minimize the systemic side effects by reducing the overall dose of FK506. RAW 264.7 cell uptake presented the enhancement of drugs delivered into cells by HA–Chol NPs–NIC. The antiproliferative activity on HaCaT cells identified that FK506 HA–Chol NPs

  17. Cytotoxic and antiproliferative activity of Securidaca longepedunculata aqueous extract on Ehrlich ascites carcinoma cells in Swiss albino mice.

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    R A Lawal

    2012-12-01

    Full Text Available Summary: Securidaca longepedunculata is a savannah shrub found growing in tropical Africa. It is reputed to have more than a hundred medicinal uses and is a major component of anticancer decoctions in Nigeria. An attempt was made in this study to determine the in vitro and in vivo cytotoxic activity and possible pro-apoptotic effect of Securidaca longepedunculata aqueous root bark extract on Ehrlich ascites carcinoma cells. In vitro cytotoxic activity was determined using the Trypan blue assay by incubating Ehrlich ascites carcinoma cells with various concentrations of Securidaca longepedunculata aqueous extract. In vivo study was carried out by intraperitoneal administration of varied doses of Securidaca longepedunculata to tumour-bearing mice. Isolated DNA from Ehrlich ascites carcinoma cells in treated and untreated animals was used for DNA fragmentation assay on agarose gel. Securidaca longepedunculata Aqueous extract, Securidaca longepedunculata was cytotoxic to Ehrlich ascites both in vivo and in vitro. The IC50 of Securidaca longepedunculata was 67 µg/ml. Securidaca longepedunculata caused a decrease in angiogenesis as observed in the reduction in weight of treated animals and a reduction in volume of ascitic fluid in treated mice.  DNA fragmentation assay of Ehrlich ascites carcinoma cells from treated animals depicted a possible pro-apoptotic effect of the Securidaca longepedunculata extract due to the ladder forming pattern which was comparable to that of the standard drug (fluorouracil. Securidaca longepedunculata aqueous extract had a cytotoxic and pro-apoptotic effect on Ehrlich ascites carcinoma cells. Industrial relevance: The use of Securidaca longepedunculata in traditional medicine in the treatment and management of cancer has been brought to the fore. Development of herbal drugs from the crude extracts could be achieved due to findings suggesting the plant could increase life span in patients with advanced stages of cancer

  18. In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

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    Teerasripreecha Dungporn

    2012-03-01

    Full Text Available Abstract Background Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Methods Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474, undifferentiated lung (Chaco, liver hepatoblastoma (Hep-G2, gastric carcinoma (KATO-III and colon adenocarcinoma (SW620 cancers. The human foreskin fibroblast cell line (Hs27 was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. Results The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC50 values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and . Conclusion This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol with potential anti

  19. In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

    Science.gov (United States)

    2012-01-01

    Background Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Methods Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474), undifferentiated lung (Chaco), liver hepatoblastoma (Hep-G2), gastric carcinoma (KATO-III) and colon adenocarcinoma (SW620) cancers. The human foreskin fibroblast cell line (Hs27) was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. Results The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC50 values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and propolis extracts. Conclusion This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol) with potential anti

  20. Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae).

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    Er, Hui Meng; Cheng, En-Hsiang; Radhakrishnan, Ammu Kutty

    2007-09-25

    The anti-proliferative effects of the aqueous and methanol extracts of leaves of Pereskia bleo (Kunth) DC (Cactaceae) against a mouse mammary cancer cell line (4T1) and a normal mouse fibroblast cell line (NIH/3T3) were evaluated under an optimal (in culture medium containing 10% foetal bovine serum (FBS)) and a sub-optimal (in culture medium containing 0.5% FBS) conditions. Under the optimal condition, the aqueous extract showed a significant (pCactaceae) do not have appreciable anti-proliferative effect on the 4T1 and NIH/3T3 cells as the EC(50) values obtained are greater than 50 microg/mL when tested under optimal culture condition. Moreover, the aqueous extract may form mutagenic compound(s) upon the metabolisation by liver enzymes.

  1. Antiproliferative activity and induction of apoptosis in estrogen receptor-positive and negative human breast carcinoma cell lines by Gmelina asiatica roots

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    Madhu Katyayani Balijepalli

    2010-01-01

    Full Text Available Low risk of breast cancer has been proposed to be associated with high intake of lignans. We have reported the presence of lignans in Gmelina asiatica roots. There are no scientific reports on the antiproliferative activity of G. asiatica roots. The objective of the present study was to evaluate the effect of ethyl acetate extract from G. asiatica roots (EGAR on estrogen receptor-positive (MCF-7 and negative (MDA-MB-231 human breast cancer cell lines. The effects of 50% inhibitory concentrations (IC 50 of EGAR on MCF-7 and MDA-MB-231 cells were determined using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay kit. The mode of cell death caused by EGAR was determined using dual apoptosis assay kit by observing the cells under fluorescent microscope. The quantification of apoptosis and necrosis in cells caused by EGAR was determined using cell death detection kit through ELISA. Down-regulation of the proliferative activity occurred in a clear dose-dependent response with IC 50 values of 32.9 ± 3.8 μg/mL in MCF-7 and 19.9 ± 2.3 μg/mL in MDA-MB-231 cell lines. Treatment of breast cancer cells with EGAR resulted in significant apoptosis. The EGAR contain lignans and flavonoids. The antiproliferative activity of the extract is attributed to the presence of these secondary metabolites. The results suggest the efficacy of G. asiatica roots as antiproliferative agents on human breast cancer cells, supporting the hypothesis that plants containing lignans have beneficial effects on human breast cancer.

  2. Spectroscopic characterization and antiproliferative activity on HepG2 human hepatoblastoma cells of flavonoid C-glycosides from Petrorhagia velutina.

    Science.gov (United States)

    Pacifico, Severina; Scognamiglio, Monica; D'Abrosca, Brigida; Piccolella, Simona; Tsafantakis, Nikolaos; Gallicchio, Marialuisa; Ricci, Andreina; Fiorentino, Antonio

    2010-12-27

    Eight flavonoid C-glycosides, including three new analogues, have been isolated from leaf and root methanolic extracts of Petrorhagia velutina, a Mediterranean herbaceous plant. The antiproliferative activity against human hepatoblastoma cancer cell line HepG2 has been analyzed by the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) test. Isoorientin (4) significantly reduces the proliferation of HepG2 cells as determined by the complete conversion of the tetrazolium probe into formazan after 48 h of exposure.

  3. Acute moderate exercise enhances compensatory brain activation in older adults.

    Science.gov (United States)

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.

  4. Activation of the ALK-5 Pathway is not per se Sufficient for the Antiproliferative Effect of TGF-β1 on Renal Tubule Epithelial Cells

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    Omar García-Sánchez

    2015-10-01

    Full Text Available Background/Aims: Defective tissue repair underlies renal tissue degeneration during chronic kidney disease (CKD progression. Unbalanced presence of TGF-β opposes effective cell proliferation and differentiation processes, necessary to replace damaged epithelia. TGF-β also retains arrested cells in a fibrotic phenotype responsible for irreversible scarring. In order to identify prospective molecular targets to prevent the effect of TGF-β during CKD, we studied the signaling pathways responsible for the antiproliferative effect of this cytokine. Methods: Tubule epithelial HK2 and MDCK cells were treated with TGF-β (or not as control to study cell proliferation (by MTT, cell signaling (by Western blot, cell cycle (by flow cytometry and apoptosis (DNA fragmentation. Results: TGF-β fully activates the ALK-5 receptor pathway, whereas it has no effect on the ALK-1 and MAPK pathways in both HK2 and MDCK cells. Interestingly, TGF-β exerts an antiproliferative effect only on MDCK cells, through a cytostatic effect in G0/G1. Inhibition of the ALK-5 pathway with SB431542 prevents the cytostatic effect of TGF-β on MDCK cells. Conclusion: Activation of the ALK-5 pathway is not sufficient for the antiproliferative effect of TGF-β. The presence of undetermined permissive conditions or absence of undetermined inhibitory conditions seems to be necessary for this effect. The ALK-5 pathway appears to provide targets to modulate fibrosis, but further research is necessary to identify critical circumstances allowing or inhibiting its role at modulating tubule epithelial cell proliferation and tubule regeneration in the context of CKD progression.

  5. Antiproliferative and Apoptosis-Inducing Activities of 4-Isopropyl-2,6-bis(1-phenylethylphenol Isolated from Butanol Fraction of Cordyceps bassiana

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    Ji Hye Kim

    2015-01-01

    Full Text Available The Cordyceps species have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF of Cordyceps bassiana. For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethylphenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component from Cordyceps bassiana, contributing to the anticancer activity of this mushroom.

  6. Antiproliferative and Apoptosis-Inducing Activities of 4-Isopropyl-2,6-bis(1-phenylethyl)phenol Isolated from Butanol Fraction of Cordyceps bassiana

    Science.gov (United States)

    Kim, Ji Hye; Sung, Gi-Ho; Kim, Han Gyung; Park, Jae Gwang; Baek, Kwang-Soo; Yoon, Deok Hyo; Lee, Sang Yeol; Kang, Hyojeung; Song, Changsik; Cho, Jae Han; Lee, Kang-Hyo; Kim, Tae Woong

    2015-01-01

    The Cordyceps species have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF) of Cordyceps bassiana. For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethyl)phenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component from Cordyceps bassiana, contributing to the anticancer activity of this mushroom. PMID:25918546

  7. Synthesis and evaluation of the antiproliferative activity of novel pyrrolo[1,2-a]quinoxaline derivatives, potential inhibitors of Akt kinase. Part II.

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    Desplat, Vanessa; Moreau, Stephane; Gay, Aurore; Fabre, Solene Belisle; Thiolat, Denis; Massip, Stephane; Macky, Gregory; Godde, Frederic; Mossalayi, Djavad; Jarry, Christian; Guillon, Jean

    2010-04-01

    Attenuation of protein kinases by selective inhibitors is an extremely active field of activity in anticancer drug development. Therefore, Akt, a serine/threonine protein kinase, also known as protein kinase B (PKB), represents an attractive potential target for therapeutic intervention. Recent efforts in the development and biological evaluation of small molecule inhibitors of Akt have led to the identification of novel inhibitors with various heterocycle scaffolds. Based on previous results obtained on the antiproliferative activities of new pyrrolo[1,2-a]quinoxalines, a novel series was designed and synthesized from various substituted phenyl-1H-pyrrole-2-carboxylic acid alkyl esters via a multistep heterocyclization process. These new compounds were tested for their in vitro ability to inhibit the proliferation of the human leukemic cell lines K562, U937, and HL60, and the breast cancer cell line MCF7. The first biological evaluation of our new substituted pyrrolo[1,2-a]quinoxalines showed antiproliferative activity against the tested cell lines. From a general SAR point of view, these preliminary biological results highlight the importance of substitution at the C-4 position of the pyrroloquinoxaline scaffold by a benzylpiperidinyl fluorobenzimidazole group, and also the need for a functionalization on the pyrrole ring.

  8. Gracilaria edulis exhibit antiproliferative activity against human lung adenocarcinoma cell line A549 without causing adverse toxic effect in vitro and in vivo.

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    Sakthivel, Ravi; Muniasamy, Samuthirapandi; Archunan, Govindaraju; Devi, Kasi Pandima

    2016-02-01

    In the present study, the antiproliferative potential of various solvent extracts of Gracilaria edulis (GE) was tested against various cancer cell lines. In the A549 lung cancer cell line model, GE ethyl acetate extract (GEEA) (100 μg mL(-1)) treated group showed the maximum and significant (P < 0.05) growth inhibition at 48 h. The IC50 value was found to be 24.5 ± 19.1 μg mL(-1) at 48 h. Moreover, a low level of LDH release was observed at 48 h at various concentrations of (40, 60, 80 and 100 μg mL(-1)) GEEA extract-treated group compared to a control group. Changes in the cell morphology and echinoid spikes formation were observed at 48 h. Safety evaluation of GEEA in a non-cancerous liver cell line, PBMC and in Wistar rats positively revealed that the extract did not show any adverse toxic effects. The GEEA extract was partially purified by column chromatography and the active fraction was characterized through LC-MS analysis. Furthermore, HPLC and FT-IR analysis of the active fractions confirmed the presence of phytol, a diterpene compound with potent antiproliferative activity, which positively suggests that the red alga G. edulis contains a potent anticancer active principle.

  9. Anti-proliferative effect of chalcone derivatives through inactivation of NF-κB in human cancer cells.

    Science.gov (United States)

    Venkateswararao, Eeda; Sharma, Vinay K; Yun, Jieun; Kim, Youngsoo; Jung, Sang-Hun

    2014-07-01

    To investigate the anti-proliferative effect of NF-κB inhibitor, a series of analogs of (E)-1-(2-hydroxy-6-(isopentyloxy)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (5a) were prepared and evaluated for their NF-κB inhibition and anti-proliferative activity against various human cancer cell lines. Compounds (E)-1-(2-(3,3-dimethylbutoxy)-6-hydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (5e) and (E)-4-(3-(2-(3,3-dimethylbutoxy)-6-hydroxyphenyl)-3-oxoprop-1-enyl)benzenesulfonamide (5p) showed good NF-κB inhibition as well as potent anti-proliferative activity. SAR studies showed that all the compounds with potent or moderate NF-κB inhibition displayed good anti-proliferative activity. All the analogs (5b-r) maintained a good correlation between their NF-κB inhibition and anti-proliferative activity though the extent is not directly proportional to each other.

  10. Extraction of Natural Antioxidants from the Thelephora ganbajun Mushroom by an Ultrasound-Assisted Extraction Technique and Evaluation of Antiproliferative Activity of the Extract against Human Cancer Cells.

    Science.gov (United States)

    Xu, Dong-Ping; Zheng, Jie; Zhou, Yue; Li, Ya; Li, Sha; Li, Hua-Bin

    2016-10-01

    The Thelephora ganbajun mushroom has been found to be a potential rich source of natural antioxidants. In this study, an ultrasound-assisted extraction (UAE) technique together with GRAS (generally recognized as safe) solvents (ethanol and water) was used to maximize the extraction of antioxidants from Thelephora ganbajun. Five extraction parameters (ethanol concentration, solvent to solid ratio, extraction time, temperature and ultrasound power) were investigated by single-factor experiments, and then a central composite rotatable design was employed to study interaction of three key extraction parameters. The optimum conditions were as follows: 57.38% ethanol, 70.15 mL/g solvent to solid ratio, 10.58 min extraction time, 40 °C extraction temperature and 500 W ultrasound power. Under the optimum conditions, the antioxidant activity obtained was 346.98 ± 12.19 µmol Trolox/g DW, in accordance with the predicted value of 344.67 µmol Trolox/g DW. Comparison of UAE with conventional maceration and Soxhlet extraction, the UAE method showed stronger extract efficiency in a shorter extraction time. These results showed that UAE was an effective technique to extract antioxidants from Thelephora ganbajun. Furthermore, the extracts obtained under the optimized conditions exhibited antiproliferative activities toward human lung (A549), breast (MCF-7), liver (HepG2) and colon (HT-29) cancer cells, especially for liver and lung cancer cells. In addition, rutin, 2-hydrocinnamic acid and epicatechin were identified in the extract, which might contribute to antioxidant and antiproliferative activities.

  11. Astemizole synergizes calcitriol antiproliferative activity by inhibiting CYP24A1 and upregulating VDR: a novel approach for breast cancer therapy.

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    Janice García-Quiroz

    Full Text Available BACKGROUND: Calcitriol antiproliferative effects include inhibition of the oncogenic ether-à-go-go-1 potassium channel (Eag1 expression, which is necessary for cell cycle progression and tumorigenesis. Astemizole, a new promising antineoplastic drug, targets Eag1 by blocking ion currents. Herein, we characterized the interaction between calcitriol and astemizole as well as their conjoint antiproliferative action in SUM-229PE, T-47D and primary tumor-derived breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Molecular markers were studied by immunocytochemistry, Western blot and real time PCR. Inhibitory concentrations were determined by dose-response curves and metabolic activity assays. At clinically achievable drug concentrations, synergistic antiproliferative interaction was observed between calcitriol and astemizole, as calculated by combination index analysis (CI <1. Astemizole significantly enhanced calcitriol's growth-inhibitory effects (3-11 folds, P<0.01. Mean IC(20 values were 1.82 ± 2.41 nM and 1.62 ± 0.75 µM; for calcitriol (in estrogen receptor negative cells and astemizole, respectively. Real time PCR showed that both drugs alone downregulated, while simultaneous treatment further reduced Ki-67 and Eag1 gene expression (P<0.05. Astemizole inhibited basal and calcitriol-induced CYP24A1 and CYP3A4 mRNA expression (cytochromes involved in calcitriol and astemizole degradation in breast and hepatoma cancer cells, respectively, while upregulated vitamin D receptor (VDR expression. CONCLUSIONS/SIGNIFICANCE: Astemizole synergized calcitriol antiproliferative effects by downregulating CYP24A1, upregulating VDR and targeting Eag1. This study provides insight into the molecular mechanisms involved in astemizole-calcitriol combined antineoplastic effect, offering scientific support to test both compounds in combination in further preclinical and clinical studies of neoplasms expressing VDR and Eag1. VDR-negative tumors might also be

  12. Antiproliferative activity of goniothalamin enantiomers involves DNA damage, cell cycle arrest and apoptosis induction in MCF-7 and HB4a cells.

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    Semprebon, Simone Cristine; Marques, Lilian Areal; D'Epiro, Gláucia Fernanda Rocha; de Camargo, Elaine Aparecida; da Silva, Glenda Nicioli; Niwa, Andressa Megumi; Macedo Junior, Fernando; Mantovani, Mário Sérgio

    2015-12-25

    (R)-goniothalamin (R-GNT) is a styryl lactone that exhibits antiproliferative property against several tumor cell lines. (S)-goniothalamin (S-GNT) is the synthetic enantiomer of R-GNT, and their biological properties are poorly understood. The aim of this study was to evaluate the antiproliferative mechanisms of (R)-goniothalamin and (S)-goniothalamin in MCF-7 breast cancer cells and HB4a epithelial mammary cells. To determine the mechanisms of cell growth inhibition, we analyzed the ability of R-GNT and S-GNT to induce DNA damage, cell cycle arrest and apoptosis. Moreover, the gene expression of cell cycle components, including cyclin, CDKs and CKIs, as well as of genes involved in apoptosis and the DNA damage response were evaluated. The natural enantiomer R-GNT proved more effective in both cell lines than did the synthetic enantiomer S-GNT, inhibiting cell proliferation via cell cycle arrest and apoptosis induction, likely in response to DNA damage. The cell cycle inhibition caused by R-GNT was mediated through the upregulation of CIP/KIP cyclin-kinase inhibitors and through the downregulation of cyclins and CDKs. S-GNT, in turn, was able to cause G0/G1 cell cycle arrest and DNA damage in MCF-7 cells and apoptosis induction only in HB4a cells. Therefore, goniothalamin presents potent antiproliferative activity to breast cancer cells MCF-7. However, exposure to goniothalamin brings some undesirable effects to non-tumor cells HB4a, including genotoxicity and apoptosis induction.

  13. Substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonamides as antimitotics. Antiproliferative, antiangiogenic and antitumoral activity, and quantitative structure-activity relationships.

    Science.gov (United States)

    Fortin, Sébastien; Wei, Lianhu; Moreau, Emmanuel; Lacroix, Jacques; Côté, Marie-France; Petitclerc, Eric; Kotra, Lakshmi P; Gaudreault, René C

    2011-11-01

    The importance of the bridge linking the two phenyl moieties of substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) was assessed using a sulfonamide group, which is a bioisostere of sulfonate and ethenyl groups. Forty one phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonamide (PIB-SA) derivatives were prepared and biologically evaluated. PIB-SAs exhibit antiproliferative activities at the nanomolar level against sixteen cancer cell lines, block the cell cycle progression in G(2)/M phase, leading to cytoskeleton disruption and anoikis. These results were subjected to CoMFA and CoMSIA analyses to establish quantitative structure-activity relationships. These results evidence that the sulfonate and sulfonamide moieties are reciprocal bioisosteres and that phenylimidazolidin-2-one could mimic the trimethoxyphenyl moiety found in the structure of numerous potent antimicrotubule agents. Finally, compounds 16 and 17 exhibited potent antitumor and antiangiogenic activities on HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membrane similar to CA-4 without significant toxicity for the chick embryos, making this class of compounds a promising class of anticancer agents.

  14. Antiproliferative activity of long chain acylated esters of quercetin-3-O-glucoside in hepatocellular carcinoma HepG2 cells

    Science.gov (United States)

    Sudan, Sudhanshu

    2015-01-01

    Despite their strong role in human health, poor bioavailability of flavonoids limits their biological effects in vivo. Enzymatically catalyzed acylation of fatty acids to flavonoids is one of the approaches of increasing cellular permeability and hence, biological activities. In this study, six long chain fatty acid esters of quercetin-3-O-glucoside (Q3G) acylated enzymatically and were used for determining their antiproliferative action in hepatocellular carcinoma cells (HepG2) in comparison to precursor compounds and two chemotherapy drugs (Sorafenib and Cisplatin). Fatty acid esters of Q3G showed significant inhibition of HepG2 cell proliferation by 85 to 90% after 6 h and 24 h of treatment, respectively. The cell death due to these novel compounds was associated with cell-cycle arrest in S-phase and apoptosis observed by DNA fragmentation, fluorescent microscopy and elevated caspase-3 activity and strong DNA topoisomerase II inhibition. Interestingly, Q3G esters showed significantly low toxicity to normal liver cells than Sorafenib (P ester of Q3G displayed the greatest antiproliferation action and a high potential as an anti-cancer therapeutic. Overall, the results of the study suggest strong antiproliferative action of these novel food-derived compounds in treatment of cancer. PMID:25681471

  15. Quaternized chitosan-coated nanofibrous materials containing gossypol: preparation by electrospinning, characterization and antiproliferative activity towards HeLa cells.

    Science.gov (United States)

    Ignatova, Milena; Manolova, Nevena; Toshkova, Reneta; Rashkov, Iliya; Gardeva, Elena; Yossifova, Liliya; Alexandrov, Marin

    2012-10-15

    Nanofibrous polylactide-based materials loaded with a natural polyphenolic compound gossypol (GOS) with antitumor properties were prepared by electrospinning. The nanofibrous materials were coated with a thin film of crosslinked quaternized chitosan (QCh). GOS incorporated in the nanofibrous mats was in the amorphous state. GOS release was diffusion-controlled and its in vitro release profiles depended on the mat composition. The nanofibrous materials exhibited high cytotoxicity towards HeLa tumor cells. Interestingly, it was particularly pronounced in the case of fibrous materials, which contain both QCh and GOS. The observed strong antiproliferative effect of the nanofibrous mats was mainly due to induction of cell apoptosis.

  16. Synthesis and in vitro antiproliferative activity of 5-alkyl-12(H)-quino[3,4-b] [1,4]benzothiazinium salts.

    Science.gov (United States)

    Zięba, Andrzej; Sochanik, Aleksander; Szurko, Agnieszka; Rams, Marzena; Mrozek, Anna; Cmoch, Piotr

    2010-11-01

    A novel method of synthesizing 1,4-thiazine ring has led to the series of 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts. The derivatives containing a butyl or decyl substituents on the quinoline nitrogen atom were obtained by alkylation of 12(H)-quino[3,4-b][1,4]benzothiazine with alkyl bromides. Antiproliferative activity in vitro of the compounds (3) was assessed using two cancer cell lines (Hct116 and LLC) and doxorubicin as a reference. Most of the studied phenothiazine derivatives showed activity against both cell lines investigated (2.2-19.6 μg/mL concentration range). A structure-activity relationship was established. Only the compounds with substituents in the 11-position of the quinobenzothiazine ring did not exhibit activity against either cell line. Copyright © 2010. Published by Elsevier Masson SAS.

  17. Dimeric Labdane Diterpenes: Synthesis and Antiproliferative Effects

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    Guillermo Schmeda-Hirschmann

    2013-05-01

    Full Text Available Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been carried out on naturally occurring diterpenes and semisynthetic derivatives, but much less is known on the effects of diterpene dimers. The aim of the present work was to synthesize dimeric diterpenes from the labdane imbricatolic acid using esters, ethers and the triazole ring as linkers. Some 18 new derivatives were prepared and the compounds were evaluated for antiproliferative activity on human normal fibroblasts (MRC-5 and the following human tumor cell lines: AGS, SK-MES-1, J82 and HL-60. The diethers 8–10, differing in the number of CH2 units in the linker, presented better antiproliferative activity with a maximum effect for the derivative 9. The best antiproliferative effect against HL-60 cells was found for compounds 3 and 17, with IC50 values of 22.3 and 23.2 μM, lower than that found for the reference compound etoposide (2.23 μM. The compounds 9, 17 and 11 were the most active derivatives towards AGS cells with IC50 values of 17.8, 23.4 and 26.1 μM. A free carboxylic acid function seems relevant for the effect as several of the compounds showed less antiproliferative effect after methylation.

  18. Reactive-oxygen-species-mediated Cdc25C degradation results in differential antiproliferative activities of vanadate, tungstate, and molybdate in the PC-3 human prostate cancer cell line.

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    Liu, Tong-Tong; Liu, Yan-Jun; Wang, Qin; Yang, Xiao-Gai; Wang, Kui

    2012-02-01

    The differential antiproliferative effects of vanadate, tungstate, and molybdate on human prostate cancer cell line PC-3 were compared and the underlying mechanisms were investigated. The results demonstrate that all of the three oxoanions can cause G(2)/M cell cycle arrest, which is evidenced by the increase in the level of phosphorylated Cdc2 at its inactive Tyr-15 site. Moreover, even if the difference in cellular uptake among the three oxoanions is excluded from the possible factors affecting their antiproliferative activity, vanadate exerted a much more potent effect in PC-3 cells than the other two oxoanions. Our results also reveal that reactive oxygen species (ROS)-mediated degradation of Cdc25C rather than Cdc25A or Cdc25B is responsible for vanadate-induced G(2)/M cell cycle arrest. We propose a possible mechanism to clarify the differential effect of the three oxoanions in biological systems beyond just considering that they are structural analogs of phosphate. We suggest that ROS formation is unlikely to be involved in the biological function of tungstate and molybdate, whereas the redox properties of vanadium may be important factors for it to exert pharmacological effects. Further, given the evidence from epidemiology studies of the association between diabetes and prostate cancer, the possibility of vanadate as a good candidate as both an antidiabetic and an anticancer agent or a chemopreventive agent is indicated.

  19. Strong effect of copper(II) coordination on antiproliferative activity of thiosemicarbazone-piperazine and thiosemicarbazone-morpholine hybrids.

    Science.gov (United States)

    Bacher, Felix; Dömötör, Orsolya; Chugunova, Anastasia; Nagy, Nóra V; Filipović, Lana; Radulović, Siniša; Enyedy, Éva A; Arion, Vladimir B

    2015-05-21

    In this study, 2-formylpyridine thiosemicarbazones and three different heterocyclic pharmacophores were combined to prepare thiosemicarbazone–piperazine mPip-FTSC (HL1) and mPip-dm-FTSC (HL2), thiosemicarbazone–morpholine Morph-FTSC (HL3) and Morph-dm-FTSC (HL4), thiosemicarbazone–methylpyrrole-2-carboxylate hybrids mPyrr-FTSC (HL5) and mPyrr-dm-FTSC (HL6) as well as their copper(II) complexes [CuCl(mPipH-FTSC-H)]Cl (1 + H)Cl, [CuCl(mPipH-dm-FTSC-H)]Cl (2 + H)Cl, [CuCl(Morph-FTSC-H)] (3), [CuCl(Morph-dm-FTSC-H)] (4), [CuCl(mPyrr-FTSC-H)(H2O)] (5) and [CuCl(mPyrr-dm-FTSC-H)(H2O)] (6). The substances were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy (HL1–HL6), ESI mass spectrometry, IR and UV–vis spectroscopy and single crystal X-ray diffraction (1–5). All compounds were prepared in an effort to generate potential antitumor agents with an improved therapeutic index. In addition, the effect of structural alterations with organic hybrids on aqueous solubility and copper(II) coordination ability was investigated. Complexation of ligands HL2 and HL4 with copper(II) was studied in aqueous solution by pH-potentiometry, UV–vis spectrophotometry and EPR spectroscopy. Proton dissociation processes of HL2 and HL4 were also characterized in detail and microscopic constants for the Z/E isomers were determined. While the hybrids HL5, HL6 and their copper(II) complexes 5 and 6 proved to be insoluble in aqueous solution, precluding antiproliferative activity studies, the thiosemicarbazone–piperazine and thiosemicarbazone–morpholine hybrids HL1–HL4, as well as copper(II) complexes 1–4 were soluble in water enabling cytotoxicity assays. Interestingly, the metal-free hybrids showed very low or even a lack of cytotoxicity (IC50 values > 300 μM) in two human cancer cell lines HeLa (cervical carcinoma) and A549 (alveolar basal adenocarcinoma), whereas their copper(II) complexes were cytotoxic showing IC50 values from 25.5 to 65.1

  20. Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

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    Jan Tauchen

    Full Text Available ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively, while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively. However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively. Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

  1. Epigenetic regulation of embryonic stem cell marker miR302C in human chondrosarcoma as determinant of antiproliferative activity of proline-rich polypeptide 1.

    Science.gov (United States)

    Galoian, Karina; Qureshi, Amir; D'Ippolito, Gianluca; Schiller, Paul C; Molinari, Marco; Johnstone, Andrea L; Brothers, Shaun P; Paz, Ana C; Temple, H T

    2015-08-01

    Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. We described recently that tumor growth inhibiting cytostatic proline-rich polypeptide 1, (PRP-1) significantly upregulated tumor suppressor miRNAs, downregulated onco-miRNAs in human chondrosarcoma JJ012 cell line, compared to chondrocytes culture. In this study we hypothesized the existence and regulation of a functional marker in cancer stem cells, correlated to peptides antiproliferative activity. Experimental results indicated that among significantly downregulated miRNA after PRP-1treatment was miRNAs 302c*. This miRNA is a part of the cluster miR302‑367, which is stemness regulator in human embryonic stem cells and in certain tumors, but is not expressed in adult hMSCs and normal tissues. PRP-1 had strong inhibitory effect on viability of chondrosarcoma and multilineage induced multipotent adult cells (embryonic primitive cell type). Unlike chondrosarcoma, in glioblastoma, PRP-1 does not have any inhibitory activity on cell proliferation, because in glioblastoma miR-302-367 cluster plays an opposite role, its expression is sufficient to suppress the stemness inducing properties. The observed correlation between the antiproliferative activity of PRP-1 and its action on downregulation of miR302c explains the peptides opposite effects on the upregulation of proliferation of adult mesenchymal stem cells, and the inhibition of the proliferation of human bone giant-cell tumor stromal cells, reported earlier. PRP-1 substantially downregulated the miR302c targets, the stemness markers Nanog, c-Myc and polycomb protein Bmi-1. miR302c expression is induced by JMJD2-mediated H3K9me2 demethylase activity in its promoter region. JMJD2 was reported to be a positive regulator for Nanog. Our experimental results proved that PRP-1 strongly inhibited H3K9 activity

  2. A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

    Energy Technology Data Exchange (ETDEWEB)

    Min, Kyung-Won [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Zhang, Xiaobo [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi, 712100 (China); Imchen, Temjenmongla [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Baek, Seung Joon, E-mail: sbaek2@utk.edu [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States)

    2012-09-01

    MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

  3. Evaluation of anti-proliferative and anti-inflammatory activities of Pelagia noctiluca venom in Lipopolysaccharide/Interferon-γ stimulated RAW264.7 macrophages.

    Science.gov (United States)

    Ayed, Yosra; Sghaier, Rabiaa Manel; Laouini, Dhafer; Bacha, Hassen

    2016-12-01

    Components of Pelagia noctiluca (P. noctiluca) venom were evaluated for their anticancer and nitric Oxide (NO) inhibition activities. Three fractions, out of four, obtained by gel filtration on Sephadex G75 of P. noctiluca venom revealed an important selective anti-proliferative activity on several cell lines such as human bladder carcinoma (RT112), human glioblastoma (U87), and human myelogenous leukemia (K562) but not on mitogen-stimulated peripheral blood mononuclear cells. Interestingly, P. noctiluca components showed an important dose-dependent anti-inflammatory activity, through inhibition of NO production via transcriptional regulation of Inducible NO Synthase (iNOS), in IFN-γ/LPS stimulated RAW 264.7 macrophages. These data strongly suggest that P. noctiluca venom could be used as a natural inhibitor of cancer cell lines and a potent anti-inflammatory agent for the treatment of anti-inflammatory diseases.

  4. A New Method for the Isolation of Ergosterol and Peroxyergosterol as Active Compounds of Hygrophoropsis aurantiaca and in Vitro Antiproliferative Activity of Isolated Ergosterol Peroxide

    Directory of Open Access Journals (Sweden)

    Renata Nowak

    2016-07-01

    Full Text Available In the present study, ergosterol peroxide and ergosterol were isolated for the first time from fresh fruit bodies of Hygrophoropsis aurantiaca (False Chanterelle. The substances were characterized mainly by spectroscopic methods (1H-NMR, 13C-NMR, DEPT-45, DEPT-90, DEPT-135, 2D-NMR. In our study, a new specific thin layer chromatographic method was developed for determination of ergosterol and ergosterol peroxide in H. aurantiaca extract. The method is based on the separation of n-hexane extract on silica gel (Silica Gel G TLC plates using the optimized solvent system toluene/ethyl acetate (3:1; v/v. The main advantages of the developed method are the simplicity of operation and the low cost. The in vitro study results revealed the antiproliferative properties of ergosterol peroxide against LS180 human colon cancer cells. The described effect was attributed both to altered mitochondrial activity and decreased DNA synthesis. Additionally, in the same concentration range the investigated compound was not toxic to CCD 841 CoTr human colon epithelial cells. The present study suggests that fruit bodies of H. aurantiaca have great potential for producing substances and extracts with potential applications in medicine.

  5. Physical activity moderates stressor-induced rumination on cortisol reactivity

    Science.gov (United States)

    Puterman, Eli; O’Donovan, Aoife; Adler, Nancy E.; Tomiyama, A. Janet; Kemeny, Margaret; Wolkowitz, Owen M.; Epel, Elissa

    2011-01-01

    Objective Physically active individuals have lower rates of morbidity and mortality, and recent evidence indicates that physical activity may be particularly beneficial to those experiencing chronic stress. The tendency to ruminate increases and prolongs physiological stress responses, including hypothalamic-pituitary adrenal (HPA) axis responses as indexed by cortisol reactivity to stressful experiences. We examined the association between ruminating in response to a laboratory stressor task and HPA axis reactivity and recovery, and whether a physically active lifestyle moderates the associations between rumination and cortisol output trajectories. Methods Forty-six post-menopausal women underwent the Trier Social Stress Test while salivary cortisol was repeatedly measured. Twenty-five minutes after the end of the stressor, participants reported level of rumination in response to the stress. Results Findings indicate that physical activity moderated the initial rate (B = −.10, SE = .04, p < .05) and curvature (B = −.03, SE = .01, p = .06) of the relationship between rumination and log-transformed cortisol trajectory. Among sedentary participants, those who responded to the stressor with higher levels of rumination had a more rapid initial increase in cortisol (0.26 vs 0.21, p < .001), a later peak (56 vs. 39 minutes), and a delayed recovery (curvature −0.07 vs. −0.08, p < .001) compared to those with lower levels of rumination. In active participants, cortisol trajectories were equivalent, regardless of level of rumination. Conclusions In sum, individuals who maintain a physically active lifestyle may be protected against the effects of rumination on HPA axis reactivity to and recovery from acute stress. PMID:21873586

  6. Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J. [The First Affiliated Hospital, Liaoning Medical University, Jinzhou (China); Key Laboratory of Cardiovascular and Cerebrovascular Drug Research, Liaoning Province, Liaoning Medical University, Jinzhou (China); Lu, M.L.; Dai, H.L.; Zhang, S.P.; Wang, H.X. [Key Laboratory of Cardiovascular and Cerebrovascular Drug Research, Liaoning Province, Liaoning Medical University, Jinzhou (China); Wei, N. [The First Affiliated Hospital, Liaoning Medical University, Jinzhou (China)

    2014-12-12

    This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg{sup -1}·day{sup -1}), or 5-Fu (200 mg·kg{sup -1}·day{sup -1}) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC{sub 50} value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

  7. Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

    Directory of Open Access Journals (Sweden)

    J. Wang

    2015-03-01

    Full Text Available This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each given daily intraperitoneal injections of vehicle (physiological saline, esculetin (200, 400, or 700 mg·kg-1·day-1, or 5-Fu (200 mg·kg-1·day-1 for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

  8. [Changes in mood caused by staged, moderate physical activity].

    Science.gov (United States)

    Otto, J; Stemmann, O

    1991-01-01

    This experiment provides a test for the common sense knowledge that moderate physical exercise leads to mood improvement. Furthermore, it was tested whether light exercise intensifies negative feeling states or alleviates them. 30 female and 30 male students of psychology served as subjects (mean age 25.3 years, SD = 4.8). After being exposed to a mood induction procedure designed to elicit either a positive or negative feeling state, the subjects had to pedal a bicycle ergometer with 0, 50 or 75 Watt load. Cardiovascular variables and self-reports of mood states were assessed during a baseline period, after the mood induction, following the ergometer exercise, and after a follow-up period. The mood induction procedures were successful, but only for a short duration. Physiological activation was observed according to the ergometer loadings. Moderate physical exercise led to an increase of positive feeling states (Concentration) and a decrease of negative feeling states (Tiredness) in the follow-up period. Corresponding changes in tension related states could not be observed, probably due to the weakness of the mood induction procedure employed and the low level of energetic activation reached.

  9. Phosphoramidate protides of five flavones and their antiproliferative activity against HepG2 and L-O2 cell lines.

    Science.gov (United States)

    Li, Yue-Qing; Yang, Fei; Wang, Liu; Cao, Zhi; Han, Tian-Jiao; Duan, Zhe-Ang; Li, Zhen; Zhao, Wei-Jie

    2016-04-13

    A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 μmol/L, 5.5 μmol/L and 6.6 μmol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. An antiproliferative xanthone of Symphonia pauciflora from the Madagascar rainforest1

    Science.gov (United States)

    Pan, Ende; Cao, Shugeng; Brodie, Peggy J.; Miller, James S.; Rakotodrajaona, Rolland; Ratovoson, Fidy; Birkinshaw, Chris; Andriantsiferana, Rabodo; Rasamison, Vincent E.; Kingston, David G. I.

    2010-01-01

    Investigation of an endemic Malagasy plant identified as Symphonia pauciflora Baker (Clusiaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of a new compound identified as 2-(3,3-dimethylallyl)-1,5,6-trihydroxy-7-methoxy-2″,2″-dimethylpyrano(6″,5″:3,4) xanthone (1) and the two known guttiferones A (2) and I (3). The structure elucidation of 1 was based on the analysis of its 1D and 2D NMR and mass spectroscopic data. Compound 1 showed good antiproliferative activity with an IC50 value of 3.8 μM against the A2780 human ovarian cancer cell line, while the known guttiferone analogues (2 and 3) exhibited moderate activities with IC50 values of 8.3 μM and 7.8 μM, respectively. PMID:20521541

  11. Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells

    Science.gov (United States)

    Sung, Nak Yoon; Kim, Seung Cheol; Kim, Yun Hwan; Kim, Gihyeon; Lee, Yunmi; Sung, Gi-Ho; Kim, Ji Hye; Yang, Woo Seok; Kim, Mi Seon; Baek, Kwang-Soo; Kim, Jong-Hoon; Cho, Jae Youl

    2016-01-01

    It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells. PMID:27068261

  12. Complexes of Pd(II) and Pt(II) with 9-Aminoacridine: Reactions with DNA and Study of Their Antiproliferative Activity

    Science.gov (United States)

    Riera, X.; Moreno, V.; Ciudad, C. J.; Noe, V.; Font-Bardía, M.; Solans, X.

    2007-01-01

    Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin. PMID:18364995

  13. Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Frédéric Couture

    2015-01-01

    Full Text Available The overexpression as well as the critical implication of the proprotein convertase PACE4 in prostate cancer progression has been previously reported and supported the development of peptide inhibitors. The multi-Leu peptide, a PACE4-specific inhibitor, was further generated and its capability to be uptaken by tumor xenograft was demonstrated with regard to its PACE4 expression status. To investigate whether the uptake of this inhibitor was directly dependent of PACE4 levels, uptake and efflux from cancer cells were evaluated and correlations were established with PACE4 contents on both wild type and PACE4-knockdown cell lines. PACE4-knockdown associated growth deficiencies were established on the knockdown HepG2, Huh7, and HT1080 cells as well as the antiproliferative effects of the multi-Leu peptide supporting the growth capabilities of PACE4 in cancer cells.

  14. Extraction of Natural Antioxidants from the Thelephora ganbajun Mushroom by an Ultrasound-Assisted Extraction Technique and Evaluation of Antiproliferative Activity of the Extract against Human Cancer Cells

    Science.gov (United States)

    Xu, Dong-Ping; Zheng, Jie; Zhou, Yue; Li, Ya; Li, Sha; Li, Hua-Bin

    2016-01-01

    The Thelephora ganbajun mushroom has been found to be a potential rich source of natural antioxidants. In this study, an ultrasound-assisted extraction (UAE) technique together with GRAS (generally recognized as safe) solvents (ethanol and water) was used to maximize the extraction of antioxidants from Thelephora ganbajun. Five extraction parameters (ethanol concentration, solvent to solid ratio, extraction time, temperature and ultrasound power) were investigated by single-factor experiments, and then a central composite rotatable design was employed to study interaction of three key extraction parameters. The optimum conditions were as follows: 57.38% ethanol, 70.15 mL/g solvent to solid ratio, 10.58 min extraction time, 40 °C extraction temperature and 500 W ultrasound power. Under the optimum conditions, the antioxidant activity obtained was 346.98 ± 12.19 µmol Trolox/g DW, in accordance with the predicted value of 344.67 µmol Trolox/g DW. Comparison of UAE with conventional maceration and Soxhlet extraction, the UAE method showed stronger extract efficiency in a shorter extraction time. These results showed that UAE was an effective technique to extract antioxidants from Thelephora ganbajun. Furthermore, the extracts obtained under the optimized conditions exhibited antiproliferative activities toward human lung (A549), breast (MCF-7), liver (HepG2) and colon (HT-29) cancer cells, especially for liver and lung cancer cells. In addition, rutin, 2-hydrocinnamic acid and epicatechin were identified in the extract, which might contribute to antioxidant and antiproliferative activities. PMID:27706082

  15. Extraction of Natural Antioxidants from the Thelephora ganbajun Mushroom by an Ultrasound-Assisted Extraction Technique and Evaluation of Antiproliferative Activity of the Extract against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Dong-Ping Xu

    2016-10-01

    Full Text Available The Thelephora ganbajun mushroom has been found to be a potential rich source of natural antioxidants. In this study, an ultrasound-assisted extraction (UAE technique together with GRAS (generally recognized as safe solvents (ethanol and water was used to maximize the extraction of antioxidants from Thelephora ganbajun. Five extraction parameters (ethanol concentration, solvent to solid ratio, extraction time, temperature and ultrasound power were investigated by single-factor experiments, and then a central composite rotatable design was employed to study interaction of three key extraction parameters. The optimum conditions were as follows: 57.38% ethanol, 70.15 mL/g solvent to solid ratio, 10.58 min extraction time, 40 °C extraction temperature and 500 W ultrasound power. Under the optimum conditions, the antioxidant activity obtained was 346.98 ± 12.19 µmol Trolox/g DW, in accordance with the predicted value of 344.67 µmol Trolox/g DW. Comparison of UAE with conventional maceration and Soxhlet extraction, the UAE method showed stronger extract efficiency in a shorter extraction time. These results showed that UAE was an effective technique to extract antioxidants from Thelephora ganbajun. Furthermore, the extracts obtained under the optimized conditions exhibited antiproliferative activities toward human lung (A549, breast (MCF-7, liver (HepG2 and colon (HT-29 cancer cells, especially for liver and lung cancer cells. In addition, rutin, 2-hydrocinnamic acid and epicatechin were identified in the extract, which might contribute to antioxidant and antiproliferative activities.

  16. Induction of antiproliferative effect by diosgenin through activation of p53,release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells

    Institute of Scientific and Technical Information of China (English)

    Cecile CORBIERE; Bertrand LIAGRE; Faraj TERRO; Jean-Louis BENEYTOUT

    2004-01-01

    Previously, we demonstrated that a plant steroid, diosgenin, altered cell cycle distribution and induced apoptosis in the human osteosarcoma 1547 cell line. The objective of this study was to investigate if the antiproliferative effect of diosgenin was similar for different human cancer cell lines such as laryngocarcinoma HEp-2 and melanoma M4Beu cells. Moreover, this work essentially focused on the mitochondrial pathway. We found that diosgenin had an important and similar antiproliferative effect on different types of cancer cells. In addition, our new results show that diosgenininduced apoptosis is caspase-3 dependent with a fall of mitochondrial membrane potential, nuclear localization of AIF and poly (ADP-ribose) polymerase cleavage. Diosgenin treatment also induces p53 activation and cell cycle arrest in the different cell lines studied.

  17. Synthesis, characterization, in silico approach and in vitro antiproliferative activity of RPF151, a benzodioxole sulfonamide analogue designed from capsaicin scaffold

    Science.gov (United States)

    Tavares, Maurício T.; Pasqualoto, Kerly F. M.; van de Streek, Jacco; Ferreira, Adilson K.; Azevedo, Ricardo A.; Damião, Mariana C. F. C. B.; Rodrigues, Cecilia P.; de-Sá-Júnior, Paulo L.; Barbuto, José A. M.; Parise-Filho, Roberto; Ferreira, Fabio F.

    2015-05-01

    RPF151, an alkylsulfonamide capsaicin analogue, was synthesized by a simple and efficient one-step methodology. The compound was characterized by 1H and 13C NMR, elemental analysis, IR and melting point. The crystal structure of RPF151 was determined by X-ray powder diffraction and its experimental arrangement was compared to the lowest-energy conformer from molecular dynamics simulation. The computational and experimental findings regarding the RPF151 structural arrangement have corroborated with one another. The compound was also tested in vitro against human umbilical vein endothelial cells (HUVEC) in order to verify its antiproliferative activity. RPF151 has significantly reduced the growth of HUVEC cells at 10 μM, suggesting that it probably would act on the angiogenesis process. RPF151 can be considered, then, as a promising anticancer lead for designing novel antitumor agents as potential drug candidates.

  18. Microwave-assisted synthesis of sec/tert-butyl 2-arylbenzimidazoles and their unexpected antiproliferative activity towards ER negative breast cancer cells.

    Science.gov (United States)

    Abdul Rahim, Aisyah Saad; Salhimi, Salizawati Muhamad; Arumugam, Natarajan; Pin, Lim Chung; Yee, Ng Shy; Muttiah, Nithya Niranjini; Keat, Wong Boon; Abd Hamid, Shafida; Osman, Hasnah; Mat, Ishak b

    2013-12-01

    A new series of N-sec/tert-butyl 2-arylbenzimidazole derivatives was synthesised in 85-96% yields within 2-3.5 min by condensing ethyl 3-amino-4-butylamino benzoate with various substituted metabisulfite adducts of benzaldehyde under focused microwave irradiation. The benzimidazole analogues were characterised using (1)H NMR, (13)C NMR, high resolution MS and melting points. Evaluation of antiproliferative activity of the benzimidazole analogues against MCF-7 and MDA-MB-231 revealed several compounds with unexpected selective inhibitions of MDA-MB-231 in micromolar range. All analogues were found inactive towards MCF-7. The most potent inhibition against MDA-MB-231 human breast cancer cell line came from the unsubstituted 2-phenylbenzimidazole 10a.

  19. Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

    Science.gov (United States)

    Kong, Zwe-Ling; Chang, Jenq-Sheng; Chang, Ke Liang B.

    2013-09-01

    Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

  20. Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Zwe-Ling, E-mail: kongzl@mail.ntou.edu.tw; Chang, Jenq-Sheng; Chang, Ke Liang B. [National Taiwan Ocean University, Department of Food Science (China)

    2013-09-15

    Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

  1. In vitro antiproliferative study of novel adamantyl pyridin-4-ones.

    Science.gov (United States)

    Petrović Peroković, V; Car, Ž; Opačak-Bernardi, T; Martin-Kleiner, I; Kralj, M; Tomić, S

    2017-07-10

    The preparation of several N-aryl-substituted (phenyl, p-methylphenyl, p-methoxyphenyl, p-nitrophenyl, p-aminophenyl, p-hydroxyphenyl) 3-hydroxy-2-methylpyridin-4-ones as well as their adamantyl derivatives is described, and their in vitro antitumor properties were investigated. The compounds were synthesized in good yields using efficient synthetic routes and methods. Prepared derivatives were evaluated in an antiproliferative in vitro study on 4 cancer cell lines, namely HCT 116 (colon carcinoma), H 460 (lung carcinoma), MCF-7 (breast carcinoma) and K562 (chronic myelogenous leukemia). All tested compounds showed antiproliferative activity ranging from moderate to strong on all inspected cell lines with 4 adamantane containing derivatives being active and selective at low micromolar IC[Formula: see text] concentrations on HCT 116, H 460 and MCF-7. LDH cytotoxicity assay revealed that cytotoxic effects occur after 48 h of exposure. It was shown that there was no change in caspase activity in the treated cells, but there were changes in the cell cycle. All treated samples showed reduced number of cells in the S phase with increased G0/G1 (4b, 5a, 5b) and G2/M (4a) phase.

  2. Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells.

    Science.gov (United States)

    Poindexter, Kevin M; Matthew, Susanne; Aronchik, Ida; Firestone, Gary L

    2016-04-01

    Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells. In both cell lines, combinations of aspirin and I3C cooperatively arrested cell proliferation and induced a G1 cell cycle arrest, and nearly ablated protein and transcript levels of the melanocyte master regulator microphthalmia-associated transcription factor isoform M (MITF-M). In melanoma cells transfected with a -333/+120-bp MITF-M promoter-luciferase reporter plasmid, treatment with aspirin and I3C cooperatively disrupted MITF-M promoter activity, which accounted for the loss of MITF-M gene products. Mutational analysis revealed that the aspirin required the LEF1 binding site, whereas I3C required the BRN2 binding site to mediate their combined and individual effects on MITF-M promoter activity. Consistent with LEF1 being a downstream effector of Wnt signaling, aspirin, but not I3C, downregulated protein levels of the Wnt co-receptor LDL receptor-related protein-6 and β-catenin and upregulated the β-catenin destruction complex component Axin. Taken together, our results demonstrate that aspirin-regulated Wnt signaling and I3C-targeted signaling pathways converge at distinct DNA elements in the MITF-M promoter to cooperatively disrupt MITF-M expression and melanoma cell proliferation.

  3. Evaluation of antioxidant activity and antiproliferative effect of fruit juices enriched with Pycnogenol® in colon carcinoma cells. The effect of in vitro gastrointestinal digestion.

    Science.gov (United States)

    Frontela-Saseta, Carmen; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Peso-Echarri, Patricia; Ros-Berruezo, Gaspar; Martínez-Graciá, Carmen; Canali, Raffaella; Virgili, Fabio

    2011-12-01

    The aim of this study was to examine the effect of in vitro gastrointestinal digestion on the antioxidant and antiproliferative effect of fruit juices enriched with Pycnogenol® (0.5 g/L) on a colon carcinoma cell line (Caco-2). The total phenolic concentration (TPC), antioxidant activity and inhibition cell growth were studied in fresh and digested pineapple juice and red fruits juice (both enriched with pine bark extract and not). After in vitro digestion the level of detectable phenolic compounds (expressed as gallic acid equivalent) was higher in both pineapple and red fruits juices enriched with Pycnogenol® than in non-enriched commercial juices (155.6 mg/100 mL vs 94.6 mg/100 mL and 478.5 mg/100 mL vs 406.9 mg/100 mL, respectively). Increased antioxidant activity (measured by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and oxygen radical absorbance capacity assay (ORAC) methods) was observed in digested enriched juices with respect to the same samples before digestion. Pycnogenol® enrichment led to a high antiproliferative effect between 24 and 72 h of incubation with undigested pineapple juice compared with the non-enriched juice. It can be concluded that enrichment of fruit juices with Pycnogenol® provides a source of phenolic compounds with high stability to in vitro gastrointestinal conditions; however, the antioxidant properties of fruit juices were affected to a different extent.

  4. Antiproliferative Activity of G-quadruplex Nucleic Acids%具抗肿瘤活性的G-四链体核酸研究进展

    Institute of Scientific and Technical Information of China (English)

    常天俊; 龚红梅; 李卫国

    2012-01-01

    G-四链体(G-quadruplex,G4)是由富含串联重复的鸟嘌呤碱基(G)的DNA或RNA链折叠形成的一种特殊的核酸二级结构.可形成G4结构的核酸序列在基因组和人端粒中广泛存在,对生理和病理过程起重要的调节作用.近年来研究发现,一些化学合成的G4核酸具有选择性的抗肿瘤增殖活性;其中AS1411是一个26个碱基的G4序列核酸,目前已作为抗癌药物进入二期临床研究.对G4核酸的结构和功能,抗癌活性及分子机理研究进行综合评述,并简要介绍G4核酸在相关领域的应用研究.%G-quadruplexes(G4s) are four-stranded nucleic acid structures adopted by some repetitive guanine-rich sequences.G4 sequences are highly prevalent in human genome and telomere.Recently,some synthetic G4s have been reported to have cancer-selective antiproliferative activity.AS1411,a 26-mer G4 DNA,is currently in phase II clinical trials as an anticancer agent.The structures,functions,antiproliferative activities and mechanisms,and the applications of G4s are reviewed.

  5. Discovery of nitroaryl urea derivatives with antiproliferative properties.

    Science.gov (United States)

    Wróbel, Tomasz M; Kiełbus, Michał; Kaczor, Agnieszka A; Kryštof, Vladimír; Karczmarzyk, Zbigniew; Wysocki, Waldemar; Fruziński, Andrzej; Król, Sylwia K; Grabarska, Aneta; Stepulak, Andrzej; Matosiuk, Dariusz

    2016-08-01

    A series of urea derivatives bearing nitroaryl moiety has been synthesized and assayed for their potential antiproliferative activities. Some of the tested compounds displayed activity in RK33 laryngeal cancer cells and TE671 rhabdomyosarcoma cells while being generally less toxic to healthy HSF human fibroblasts cells. One compound was demonstrated to be a moderate CDK2 inhibitor with IC50 = 14.3 µM. Its structure was solved by an X-ray crystallography and molecular modelling was performed to determine structure-activity relationship. Obtained compounds constitute novel structures and generally demonstrated greater cytotoxicity in comparison to cisplatin. This study offers new structural motifs with potential for further development.

  6. Phenolic Composition and Antioxidant and Antiproliferative Activities of the Extracts of Twelve Common Bean (Phaseolus vulgaris L. Endemic Ecotypes of Southern Italy before and after Cooking

    Directory of Open Access Journals (Sweden)

    Maria Neve Ombra

    2016-01-01

    Full Text Available Beans are important dietary components with versatile health benefits. We analysed the extracts of twelve ecotypes of Phaseolus vulgaris in order to determine their phenolic profiles, antioxidant activity, and the in vitro antiproliferative activity. Ultra-performance liquid chromatography with diode array detector (UPLC-DAD admitted us to detect and quantify some known polyphenols, such as gallic acid, chlorogenic acid, epicatechin, myricetin, formononetin, caffeic acid, and kaempferol. The antioxidant activity (AA ranged from 1.568 ± 0.041 to 66.572 ± 3.197 mg necessary to inhibit the activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical by 50% (EC50. The extracts, except those obtained from the nonpigmented samples, were capable of inhibiting the proliferation of the human epithelial colorectal adenocarcinoma (Caco-2 cells, human breast cancer cells MCF-7, and A549 NSCLC cell line. Cultivars differed in composition and concentration of polyphenols including anthocyanins; cooking affected the antioxidant activity only marginally. Qualitative and quantitative differences in phenolic composition between the groups of beans influenced the biological activities; on the other hand, we did not find significant differences on the biological activities within the same variety, before and after cooking.

  7. Phenolic Composition and Antioxidant and Antiproliferative Activities of the Extracts of Twelve Common Bean (Phaseolus vulgaris L.) Endemic Ecotypes of Southern Italy before and after Cooking.

    Science.gov (United States)

    Ombra, Maria Neve; d'Acierno, Antonio; Nazzaro, Filomena; Riccardi, Riccardo; Spigno, Patrizia; Zaccardelli, Massimo; Pane, Catello; Maione, Mena; Fratianni, Florinda

    2016-01-01

    Beans are important dietary components with versatile health benefits. We analysed the extracts of twelve ecotypes of Phaseolus vulgaris in order to determine their phenolic profiles, antioxidant activity, and the in vitro antiproliferative activity. Ultra-performance liquid chromatography with diode array detector (UPLC-DAD) admitted us to detect and quantify some known polyphenols, such as gallic acid, chlorogenic acid, epicatechin, myricetin, formononetin, caffeic acid, and kaempferol. The antioxidant activity (AA) ranged from 1.568 ± 0.041 to 66.572 ± 3.197 mg necessary to inhibit the activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical by 50% (EC50). The extracts, except those obtained from the nonpigmented samples, were capable of inhibiting the proliferation of the human epithelial colorectal adenocarcinoma (Caco-2) cells, human breast cancer cells MCF-7, and A549 NSCLC cell line. Cultivars differed in composition and concentration of polyphenols including anthocyanins; cooking affected the antioxidant activity only marginally. Qualitative and quantitative differences in phenolic composition between the groups of beans influenced the biological activities; on the other hand, we did not find significant differences on the biological activities within the same variety, before and after cooking.

  8. Valorization of Lipids from Gracilaria sp. through Lipidomics and Decoding of Antiproliferative and Anti-Inflammatory Activity

    Science.gov (United States)

    da Costa, Elisabete; Melo, Tânia; Moreira, Ana S. P.; Bernardo, Carina; Helguero, Luisa; Ferreira, Isabel; Cruz, Maria Teresa; Rego, Andreia M.; Domingues, Pedro; Calado, Ricardo; Abreu, Maria H.; Domingues, Maria Rosário

    2017-01-01

    The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA) system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC–MS and MS/MS). One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG), digalactosyl diacylglyceride (DGDG), sulfoquinovosyl monoacylglyceride (SQMG), sulfoquinovosyl diacylglyceride (SQDG), the phospholipids phosphatidylcholine (PC), lyso-PC, phosphatidylglycerol (PG), lyso-PG, phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatic acid (PA), inositolphosphoceramide (IPC), and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS). Antiproliferative and anti-inflammatory effects promoted by lipid extract of Gracilaria sp. were evaluated by monitoring cell viability in human cancer lines and by using murine macrophages, respectively. The lipid extract decreased cell viability of human T-47D breast cancer cells and of 5637 human bladder cancer cells (estimated half-maximal inhibitory concentration (IC50) of 12.2 μg/mL and 12.9 μg/mL, respectively) and inhibited the production of nitric oxide (NO) evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) on the macrophage cell line RAW 264.7 (35% inhibition at a concentration of 100 μg/mL). These findings contribute to increase the ranking in the value-chain of Gracilaria sp. biomass cultivated under controlled conditions on IMTA systems. PMID:28257116

  9. Valorization of Lipids from Gracilaria sp. through Lipidomics and Decoding of Antiproliferative and Anti-Inflammatory Activity.

    Science.gov (United States)

    da Costa, Elisabete; Melo, Tânia; Moreira, Ana S P; Bernardo, Carina; Helguero, Luisa; Ferreira, Isabel; Cruz, Maria Teresa; Rego, Andreia M; Domingues, Pedro; Calado, Ricardo; Abreu, Maria H; Domingues, Maria Rosário

    2017-03-02

    The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA) system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC-MS and MS/MS). One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG), digalactosyl diacylglyceride (DGDG), sulfoquinovosyl monoacylglyceride (SQMG), sulfoquinovosyl diacylglyceride (SQDG), the phospholipids phosphatidylcholine (PC), lyso-PC, phosphatidylglycerol (PG), lyso-PG, phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatic acid (PA), inositolphosphoceramide (IPC), and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS). Antiproliferative and anti-inflammatory effects promoted by lipid extract of Gracilaria sp. were evaluated by monitoring cell viability in human cancer lines and by using murine macrophages, respectively. The lipid extract decreased cell viability of human T-47D breast cancer cells and of 5637 human bladder cancer cells (estimated half-maximal inhibitory concentration (IC50) of 12.2 μg/mL and 12.9 μg/mL, respectively) and inhibited the production of nitric oxide (NO) evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) on the macrophage cell line RAW 264.7 (35% inhibition at a concentration of 100 μg/mL). These findings contribute to increase the ranking in the value-chain of Gracilaria sp. biomass cultivated under controlled conditions on IMTA systems.

  10. Synthesis, crystal structure and spectroscopy of bioactive Cd(II) polymeric complex of the non-steroidal anti-inflammatory drug diclofenac sodium: Antiproliferative and biological activity

    Science.gov (United States)

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick

    2015-02-01

    The interaction of Cd(II) with the non-steroidal anti-inflammatory drug diclofenac sodium (Dic) leads to the formation of the complex [Cd2(L)41.5(MeOH)2(H2O)]n(L = Dic), 1, which has been isolated and structurally characterized by X-ray crystallography. Diclofenac sodium and its metal complex 1 have also been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The results of cytotoxic activity in vitro expressed as IC50 values indicated the diclofenac sodium and cadmium chloride are non active or less active than the metal complex of diclofenac (1). Complex 1 was also found to be a more potent cytotoxic agent against T-24 and MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cisplatin, under the same experimental conditions. The superoxide dismutase activity was measured by Fridovich test which showed that complex 1 shows a low value in comparison with Cu complexes. The binding properties of this complex to biomolecules, bovine or human serum albumin, are presented and evaluated. Antibacterial and growth inhibitory activity is also higher than that of the parent ligand compound.

  11. A Novel Lectin with Antiproliferative and HIV-1 Reverse Transcriptase Inhibitory Activities from Dried Fruiting Bodies of the Monkey Head Mushroom Hericium erinaceum

    Directory of Open Access Journals (Sweden)

    Yanrui Li

    2010-01-01

    Full Text Available A lectin designated as Hericium erinaceum agglutinin (HEA was isolated from dried fruiting bodies of the mushroom Hericium erinaceum with a chromatographic procedure which entailed DEAE-cellulose, CM-cellulose, Q-Sepharose, and FPLC Superdex 75. Its molecular mass was estimated to be 51 kDa and its N-terminal amino acid sequences was distinctly different from those of other isolated mushroom lectins. The hemagglutinating activity of HEA was inhibited at the minimum concentration of 12.5 mM by inulin. The lectin was stable at pH 1.9–12.1 and at temperatures up to 70∘C, but was inhibited by Hg2+, Cu2+, and Fe3+ ions. The lectin exhibited potent mitogenic activity toward mouse splenocytes, and demonstrated antiproliferative activity toward hepatoma (HepG2 and breast cancer (MCF7 cells with an IC50 of 56.1 M and 76.5 M, respectively. It manifested HIV-1 reverse transcriptase inhibitory activity with an IC50 of 31.7 M. The lectin exhibited potent mitogenic activity toward murine splenocytes but was devoid of antifungal activity.

  12. 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells

    Science.gov (United States)

    Kim, Tae-Kang; Janjetovic, Zorica; Tuckey, Robert C.; Bieniek, Radoslaw; Yue, Junming; Li, Wei; Chen, Jianjun; Nguyen, Minh N.; Tang, Edith K. Y.; Miller, Duane; Chen, Tai C.; Holick, Michael

    2011-01-01

    20-hydroxyvitamin D2 [20(OH)D2] inhibits DNA synthesis in epidermal keratinocytes, melanocytes, and melanoma cells in a dose- and time-dependent manner. This inhibition is dependent on cell type, with keratinocytes and melanoma cells being more sensitive than normal melanocytes. The antiproliferative activity of 20(OH)D2 is similar to that of 1,25(OH)2D3 and of newly synthesized 1,20(OH)2D2 but significantly higher than that of 25(OH)D3. 20(OH)D2 also displays tumorostatic effects. In keratinocytes 20(OH)D2 inhibits expression of cyclins and stimulates involucrin expression. It also stimulates CYP24 expression, however, to a significantly lower degree than that by 1,25(OH)2D3 or 25(OH)D3. 20(OH)D2 is a poor substrate for CYP27B1 with overall catalytic efficiency being 24- and 41-fold lower than for 25(OH)D3 with the mouse and human enzymes, respectively. No conversion of 20(OH)D2 to 1,20(OH)2D2 was detected in intact HaCaT keratinocytes. 20(OH)D2 also demonstrates anti-leukemic activity but with lower potency than 1,25(OH)2D3. The phenotypic effects of 20(OH)D2 are mediated through interaction with the vitamin D receptor (VDR) as documented by attenuation of cell proliferation after silencing of VDR, by enhancement of the inhibitory effect through stable overexpression of VDR and by the demonstration that 20(OH)D2 induces time-dependent translocation of VDR from the cytoplasm to the nucleus at a comparable rate to that for 1,25(OH)2D3. In vivo tests show that while 1,25(OH)2D3 at doses as low as 0.8 μg/kg induces calcium deposits in the kidney and heart, 20(OH)D2 is devoid of such activity even at doses as high as 4 μg/kg. Silencing of CY27B1 in human keratinocytes showed that 20(OH)D2 does not require its transformation to 1,20(OH)2D2 for its biological activity. Thus 20(OH)D2 shows cell-type dependent antiproliferative and prodifferentiation activities through activation of VDR, while having no detectable toxic calcemic activity, and is a poor substrate for CYP

  13. Synthesis and in vitro antiproliferative activity of novel 12(H)-quino[3,4-b][1,4]benzothiazine derivatives.

    Science.gov (United States)

    Zięba, Andrzej; Latocha, Małgorzata; Sochanik, Aleksander

    2013-09-01

    Novel method of N-dealkylating quinobenzothiazinium salts 2, promoted by reaction with benzimidazole, led to a series of new azaphenothiazine derivatives having 12(H)-quino[3,4-b][1,4] benzothiazine 4 structure. Reaction of compounds 4 in an alkaline milieu with alkylating agents occur as N-alkylation of the thiazine nitrogen and yields quinobenzothiazine derivatives 7. In vitro antiproliferative activity of compounds 4 and 7 was tested using two cancer cell lines (SNB-19 and C-32) and cisplatin as a reference. Most of the studied azaphenothiazine derivatives showed activity against both cell lines investigated (5.6-12.4 μg/ml concentration range tested). Compounds 4(b-e) containing a halogen atom or methyl group at the 9-position of the quinobenzothiazine ring show activity in the tested concentration range only against C-32 cell line. Compound 4f with methyl group in 11-position of quinobenzothiazine ring lacked activity against either cell line. The presence of additional aminoalkyl substituents at the thiazine nitrogen atom in compounds 7 increases their activity against both examined cell lines, when compared to compounds 4.

  14. Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

    Science.gov (United States)

    Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

    2016-09-01

    Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 μg/ml. The cytotoxic activity of compound 5c and 5f against BALB/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 μg/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopoI and hTopoII and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine.

  15. A tri-copper(II) complex displaying DNA-cleaving properties and antiproliferative activity against cancer cells.

    Science.gov (United States)

    Suntharalingam, Kogularamanan; Hunt, Douglas J; Duarte, Alexandra A; White, Andrew J P; Mann, David J; Vilar, Ramon

    2012-11-19

    A new disubstituted terpyridine ligand and the corresponding tri-copper(II) complex have been prepared and characterised. The binding affinity and binding mode of this tri-copper complex (as well as the previously reported mono- and di-copper analogues) towards duplex DNA were determined by using UV/Vis spectroscopic titrations and fluorescent indicator displacement (FID) assays. These studies showed the three complexes to bind moderately (in the order of 10(4)  M(-1)) to duplex DNA (ct-DNA and a 26-mer sequence). Furthermore, the number of copper centres and the nature of the substituents were found to play a significant role in defining the binding mode (intercalative or groove binding). The nuclease potential of the three complexes was investigated by using circular plasmid DNA as a substrate and analysing the products by agarose-gel electrophoresis. The cleaving activity was found to be dependent on the number of copper centres present (cleaving potency was in the order: tri-copper>di-copper>mono-copper). Interestingly, the tri-copper complex was able to cleave DNA without the need of external co-reductants. As this complex displayed the most promising nuclease properties, cell-based studies were carried out to establish if there was a direct link between DNA cleavage and cellular toxicity. The tri-copper complex displayed high cytotoxicity against four cancer cell lines. Of particular interest was that it displayed high cytotoxicity against the cisplatin-resistant MOLT-4 leukaemia cell line. Cellular uptake studies showed that the tri-copper complex was able to enter the cell and more importantly localise in the nucleus. Immunoblotting analysis (used to monitor changes in protein levels related to the DNA damage response pathway) and DNA-flow cytometric studies suggested that this tri-copper(II) complex is able to induce cellular DNA damage. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Valorization of Lipids from Gracilaria sp. through Lipidomics and Decoding of Antiproliferative and Anti-Inflammatory Activity

    Directory of Open Access Journals (Sweden)

    Elisabete da Costa

    2017-03-01

    Full Text Available The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC–MS and MS/MS. One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG, digalactosyl diacylglyceride (DGDG, sulfoquinovosyl monoacylglyceride (SQMG, sulfoquinovosyl diacylglyceride (SQDG, the phospholipids phosphatidylcholine (PC, lyso-PC, phosphatidylglycerol (PG, lyso-PG, phosphatidylinositol (PI, phosphatidylethanolamine (PE, phosphatic acid (PA, inositolphosphoceramide (IPC, and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS. Antiproliferative and anti-inflammatory effects promoted by lipid extract of Gracilaria sp. were evaluated by monitoring cell viability in human cancer lines and by using murine macrophages, respectively. The lipid extract decreased cell viability of human T-47D breast cancer cells and of 5637 human bladder cancer cells (estimated half-maximal inhibitory concentration (IC50 of 12.2 μg/mL and 12.9 μg/mL, respectively and inhibited the production of nitric oxide (NO evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS on the macrophage cell line RAW 264.7 (35% inhibition at a concentration of 100 μg/mL. These findings contribute to increase the ranking in the value-chain of Gracilaria sp. biomass cultivated under controlled conditions on IMTA systems.

  17. Synthesis of new cis-fused tetrahydrochromeno[4,3-b]quinolines and their antiproliferative activity studies against MDA-MB-231 and MCF-7 breast cancer cell lines.

    Science.gov (United States)

    Nagaiah, K; Venkatesham, A; Srinivasa Rao, R; Saddanapu, V; Yadav, J S; Basha, S J; Sarma, A V S; Sridhar, B; Addlagatta, A

    2010-06-01

    New cis-fused tetrahydrochromeno[4,3-b]quinolines have been synthesized by intramolecular [4+2] imino-Diels-Alder reactions of 2-azadienes derived in situ from aromatic amines and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones in the presence of 20mol% Yb(OTf)(3) in acetonitrile under reflux conditions in good to excellent yields. The structures were established by spectroscopic data and further confirmed by X-ray diffraction analysis. These compounds were evaluated for their antiproliferative activity against MDA-MB-231 and MCF-7 breast cancer cells. The results showed that compounds 3e, 3f, and 3k exhibit significant antiproliferative activity against MCF-7 breast cancer cells and low inhibitory activity against MDA-MB-231 breast cancer cell lines. Compound 3h displayed activity as comparable to tamoxifen on both the cell lines.

  18. Antiproliferative activity of buttermilk lipid fractions isolated using food grade and non-food grade solvents on human cancer cell lines.

    Science.gov (United States)

    Castro-Gómez, Pilar; Rodríguez-Alcalá, Luis M; Monteiro, Karin M; Ruiz, Ana L T G; Carvalho, João E; Fontecha, Javier

    2016-12-01

    Buttermilk is a dairy by-product with a high content of milk fat globule membranes (MFGMs), whose protein constituents are reported to be antiproliferative. Lipids represent about half of the composition of MFGM. The aim of this study was to isolate buttermilk lipid fractions and evaluate their potential antiproliferative effect. Selective extraction with food grade or non-food grade solvents was performed. Antiproliferative effectiveness of lipid extracts and their neutral and polar fractions was evaluated on nine human cancer cell lines. Fractions obtained using food grade ethanol gave a higher yield than those obtained using non-food grade solvents, and they effectively inhibited cell viability of the cancer cell lines investigated. These fractions, rich in phospho- and sphingolipids, were strongly antiproliferative against human ovary and colon cancer cells. This observation allowed us to hypothesize further analyses aimed at promoting the use of buttermilk polar lipid fractions as functional food additives.

  19. Heteropentanuclear Oxalato-Bridged nd–4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity

    KAUST Repository

    Kuhn, Paul-Steffen

    2015-08-10

    A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d–4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(μ-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by 13C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)]2− are coordinated to YIII and DyIII, respectively, with formation of [Ln{RuCl3(μ-ox)(NO)}4]5− (Ln=Y, Dy). While YIII is eight-coordinate in 2, DyIII is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N+ ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2–5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d–4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2–5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d–4f metal complexes 6–9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 μM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells.

  20. A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Youlin Deng

    2016-08-01

    Full Text Available Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.

  1. Erucin, a new promising cancer chemopreventive agent from rocket salads, shows anti-proliferative activity on human lung carcinoma A549 cells.

    Science.gov (United States)

    Melchini, A; Costa, C; Traka, M; Miceli, N; Mithen, R; De Pasquale, R; Trovato, A

    2009-07-01

    Erucin (ER) is a dietary isothiocyanate present in cruciferous vegetables, such as rocket salads (Erucasativa Mill., Diplotaxis sp.), that has been recently considered a promising cancer chemopreventive phytochemical. Biological activity of ER was investigated on human lung adenocarcinoma A549 cells, analyzing its effects on molecular pathways involved in apoptosis and cell cycle arrest, such as PARP-1 cleavage, p53 and p21 protein expression. Our results show that ER affects the A549 cell proliferation, enhancing significantly p53 and p21 protein expression in a dose-dependent manner (pinduction of p53, p21 and PARP-1 cleavage may participate in the anti-proliferative activity of ER in human lung adenocarcinoma A549 cells. Comparison of data with those obtained with the isothiocyanate sulforaphane (SF), structurally related to ER, underlines the strong relationship between structural analogy of ITCs and their biological activity. The ability of dietary compounds to modulate molecular mechanisms that affect cancer cell proliferation is certainly a key point of the cancer prevention potential by functional foods.

  2. Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines.

    Science.gov (United States)

    Demchuk, Dmitry V; Samet, Alexander V; Chernysheva, Natalia B; Ushkarov, Vladimir I; Stashina, Galina A; Konyushkin, Leonid D; Raihstat, Mikhail M; Firgang, Sergei I; Philchenkov, Alex A; Zavelevich, Michael P; Kuiava, Ludmila M; Chekhun, Vasyl F; Blokhin, Dmitry Yu; Kiselyov, Alex S; Semenova, Marina N; Semenov, Victor V

    2014-01-15

    A series of 1,5-diaryl- and 4,5-diaryl-1,2,3-triazole derivatives of combretastatin A4 were synthesized and evaluated as antimitotic microtubule destabilizing agents using the sea urchin embryo model. Structure-activity relationship studies identified compounds substituted with 3,4,5-trimethoxyphenyl and 3,4-methylenedioxy-5-methoxyphenyl ring A and 4-methoxyphenyl ring B as potent antiproliferative agents with high cytotoxicity against a panel of human cancer cell lines including multi-drug resistant cells. 4,5-Diaryl-1,2,3-triazoles (C-C geometry) were found to be considerably more active than the respective 1,5-diaryl-1,2,3-triazoles (N-C geometry). Compound 10ad' induced G2/M cell cycle arrest and apoptosis in human T-leukemia Jurkat cells via caspase 2/3/9 activation and downregulation of the antiapoptotic protein XIAP. A mitotic catastrophe has been evaluated as another possible cell death mode.

  3. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrea del Pilar Sánchez-Camargo

    2016-12-01

    Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  4. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells.

    Science.gov (United States)

    Sánchez-Camargo, Andrea Del Pilar; García-Cañas, Virginia; Herrero, Miguel; Cifuentes, Alejandro; Ibáñez, Elena

    2016-12-07

    In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116). The processes, carried out under optimal conditions, were: (1) pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent) at lab-scale; (2) Single-step supercritical fluid extraction (SFE) at pilot scale; (3) Intensified two-step sequential SFE at pilot scale; (4) Integrated PLE plus supercritical antisolvent fractionation (SAF) at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight), this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA) and carnosol (CS) at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide), suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  5. Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Hye-Youn Kim

    2015-10-01

    Full Text Available Chamaecyparis obtusa (CO belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116 were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity.

  6. Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics.

    Science.gov (United States)

    Kim, Hye-Youn; Lee, Seul-Gi; Oh, Taek-Joo; Lim, Sa Rang; Kim, So-Hyun; Lee, Hong Jin; Kim, Young-Suk; Choi, Hyung-Kyoon

    2015-10-02

    Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity.

  7. Chemical Constituents, in vitro Antioxidant and Antiproliferative Activities of Perralderia coronopifolia Coss. subsp. eu-coronopifolia M. var. typica M. extract

    Directory of Open Access Journals (Sweden)

    Sara Boussaha

    2015-04-01

    Full Text Available Phytochemical investigations of extracts from the aerial parts (leaves and flowers of Perralderia coronopifolia Cosson resulted in the isolation of nine secondary metabolites corresponding to three flavonoids: rhamnazin(1, chrysosplenol D (3, and (2R, 3R taxifolin (4, two monoterpene glycosides : myrtenol- β-D-glucopyranoside- 6'-O-acetate (2 and myrtenol β-D-glucopyranoside (7, a disaccharide: sucrose (9 and three di-O-caffeoylquinic acid derivatives : methyl 3, 5-di-O-caffeoyl quinate (5 and methyl 3,4-di-O-caffeoyl quinate (6 as a mixture and 1,5-di-O-caffeoylquinic acid (8. The structures were identified by spectroscopic methods such as 1H and 13C NMR, COSY, HSQC and HMBC experiments, HRESI-MS and comparison with literature data. Myrtenol-β-D-glucopyranoside-6'-O-acetate (2 was isolated in pure and native state for the first time. The other compounds are new for the genus Perralderia Cosson. The ethyl acetate extract showed a high antioxidant effect, especially DPPH radical scavenging activity with IC 50=7.01±0.28µg/mL compared to ascorbic acid ( IC 50= 5±0.1µg/mL . This extract also showed antiproliferative activity against HeLa (human cervix carcinoma and C6 (rat brain tumor cells.

  8. Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: in vitro antiproliferative activity and molecular mechanism(s) of action.

    Science.gov (United States)

    Parrino, Barbara; Carbone, Anna; Ciancimino, Cristina; Spanò, Virginia; Montalbano, Alessandra; Barraja, Paola; Cirrincione, Girolamo; Diana, Patrizia; Sissi, Claudia; Palumbo, Manlio; Pinato, Odra; Pennati, Marzia; Beretta, Giovanni; Folini, Marco; Matyus, Peter; Balogh, Balázs; Zaffaroni, Nadia

    2015-04-13

    Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2'-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities.

  9. Resveratrol Increases Anti-Proliferative Activity of Bestatin Through Downregulating P-Glycoprotein Expression Via Inhibiting PI3K/Akt/mTOR Pathway in K562/ADR Cells.

    Science.gov (United States)

    Wang, Li; Wang, Changyuan; Jia, Yongming; Liu, Zhihao; Shu, Xiaohong; Liu, Kexin

    2016-05-01

    Multidrug resistance (MDR) is a major obstacle in the clinical therapy of hematological malignancies. P-glycoprotein (P-gp) overexpression results in reduction of intracellular drug concentration with a consequence that the cytotoxicity of anti-tumor drugs is decreased, which leads to MDR in K562/ADR cells. In this study, we found that resveratrol enhanced the anti-proliferative activity of bestatin in K562/ADR cells. Co-treatment with resveratrol, IC50 values of bestatin in K562/ADR cells significantly decreased and activation of caspase-3 and caspase-8 increased, which indicated that resveratrol potentiated bestatin-induced apoptosis. Resveratrol increased the intracellular concentration of bestatin through inhibiting P-gp function and downregulating P-gp expression at mRNA and protein levels, which increased anti-proliferative activity of bestatin in K562/ADR cells. Resveratrol decreased the phosphorylation of Akt and mTOR but did not affect the phosphorylations of JNK or ERK1/2. These results demonstrated that resveratrol could increase the anti-proliferative activity of bestatin through downregulating P-gp expression via suppressing the PI3K/Akt/mTOR signaling pathway.

  10. Characterization and evaluation of antibacterial and antiproliferative activities of crude protein extracts isolated from the seed of Ricinus communis in Bangladesh.

    Science.gov (United States)

    Al-Mamun, M Abdulla; Akter, Zerin; Uddin, Md Josim; Ferdaus, K M K B; Hoque, K M F; Ferdousi, Z; Reza, M Abu

    2016-07-12

    Ricinus communis (Euphorbiaceae) has previously been reported to possess analgesic, antihistamine, antioxidant and anti-inflammatory activities. This study was designed for isolation, characterization and evaluation of antibacterial and anti-proliferative activities of R. communis seed protein. The concentration and molecular weight of R. communis seed protein were estimated by SDS-PAGE and spectrophotometric analysis, respectively. Lectin activity was evaluated by hemagglutination assay on mice blood. In vitro susceptibility of four human pathogenic bacteria including Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes and Staphylococcus aureus was detected using disk diffusion assay, and minimum inhibitory concentration (MIC) value was determined using micro-dilution method. A total of twenty four Swiss albino mice containing Ehrlich's ascites carcinoma (EAC) cells were treated with the crude protein of R. communis at 50 and 100 μg/ml/d/mouse for 6 days. Growth inhibitory activity of R. communis seed protein on EAC cells was determined by haemocytometer counting using trypan blue dye and DAPI (4΄,6-diamidino-2-phenylindole) staining was used to assess apoptotic cells. The protein concentration of six R. communis (castor) varieties ranged between 21-35 mg/ml and molecular weight between 14-200 kDa. Castor protein agglutinated mice blood at 3.125 μg/wall. The seed protein shows considerable antimicrobial activity against E. coli, P. aeruginosa and S. aureus, exhibiting MIC values of 250, 125 and 62.5 μg/ml, respectively. Administration of seed protein led to 54 % growth inhibition of EAC cells at 100 μg/ml. DAPI staining indicates marked features of apoptosis including condensation of cytoplasm, nuclear fragmentation and aggregation of apoptotic bodies etc. Our study suggests that the lectin rich R. communis seed protein has strong antibacterial and anticancer activities.

  11. Two new benzylisoquinoline alkaloids from Thalictrum foliolosum and their antioxidant and in vitro antiproliferative properties.

    Science.gov (United States)

    Li, Da-Hong; Guo, Jia; Bin, Wen; Zhao, Nan; Wang, Kai-Bo; Li, Jian-Yong; Li, Zhan-Lin; Hua, Hui-Ming

    2016-07-01

    Two novel rare chloro-containing benzylisoquinoline alkaloids, thalfoliolosumines A (1) and B (2), along with eight known isoquinoline alkaloids (3-10) were isolated from the whole plant of Thalictrum foliolosum. The structures of these compounds were elucidated by spectral analyses, including 1D and 2D NMR (COSY, HSQC, HMBC and NOESY) experiments. The antiproliferative effects of all the isolated compounds were evaluated by MTT method against MCF-7, PC-3, and U937 cells, and trypan blue method against HL-60 cells. New compounds 1 and 2 exhibited moderate in vitro antiproliferative activity against MCF-7, PC-3, and HL-60 cells, and good inhibitory effects against U937 cells with IC50 values of 7.50 and 6.97 μM, respectively. Compounds 7 and 10 showed the strongest in vitro antiproliferative with IC50 values of 0.93 and 1.69 μM against HL-60 cell line. The antioxidant properties were also measured, bisbenzyltetrahydroisoquinoline alkaloids 3-6 showed the strongest antioxidant activities in ABTS assay.

  12. Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells.

    Science.gov (United States)

    Mustapha, Nadia; Pinon, Aline; Limami, Youness; Simon, Alain; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-05-01

    Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC. © 2015 Wiley Periodicals, Inc.

  13. Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)- 1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues.

    Science.gov (United States)

    Carbone, A; Pennati, M; Barraja, P; Montalbano, A; Parrino, B; Spanò, V; Lopergolo, A; Sbarra, S; Doldi, V; Zaffaroni, N; Cirrincione, G; Diana, P

    2014-01-01

    A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G2/M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr(34) and to increase the cytotoxic activity of paclitaxel in STO cells.

  14. Osmium(III) analogues of KP1019: Electrochemical and chemical synthesis, spectroscopic characterization, x-ray crystallography, hydrolytic stability, and antiproliferative activity

    KAUST Repository

    Kuhn, Paul-Steffen

    2014-10-20

    A one-electron reduction of osmium(IV) complexes trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole ([1]0), 2H-indazole ([2]0), 1H-imidazole ([3]0), and 1H-benzimidazole ([4]0), afforded a series of eight new complexes as osmium analogues of KP1019, a lead anticancer drug in clinical trials, with the general formula (cation)[trans-OsIIICl4(Hazole)2], where cation = H2pz+ (H2pz[1]), H2ind+ (H2ind[2]), H2im+ (H2im[3]), Ph4P+ (Ph4P[3]), nBu4N+ (nBu4N[3]), H2bzim+ (H2bzim[4]), Ph4P+ (Ph4P[4]), and nBu4N+ (nBu4N[4]). All complexes were characterized by elemental analysis, 1H NMR spectroscopy, electrospray ionization mass spectrometry, UV-vis spectroscopy, cyclic voltammetry, while H2pz[1], H2ind[2], and nBu4[3], in addition, by X-ray diffraction. The reduced species [1]- and [4]- are stable in aqueous media in the absence of air oxygen and do not react with small biomolecules such as amino acids and the nucleotide 5′-dGMP. Cell culture experiments in five different human cancer cell lines (HeLa, A549, FemX, MDA-MB-453, and LS-174) and one noncancerous cell line (MRC-5) were performed, and the results were discussed and compared to those for KP1019 and cisplatin. Benzannulation in complexes with similar structure enhances antitumor activity by several orders of magnitude, implicating different mechanisms of action of the tested compounds. In particular, complexes H2ind[2] and H2bzim[4] exhibited significant antiproliferative activity in vitro when compared to H2pz[1] and H2im[3]. (Chemical Equation Presented).

  15. Of the major phenolic acids formed during human microbial fermentation of tea, citrus, and soy flavonoid supplements, only 3,4-dihydroxyphenylacetic acid has antiproliferative activity.

    Science.gov (United States)

    Gao, Kun; Xu, Anlong; Krul, Cyrille; Venema, Koen; Liu, Yong; Niu, Yantao; Lu, Jinxiu; Bensoussan, Liath; Seeram, Navindra P; Heber, David; Henning, Susanne M

    2006-01-01

    Dietary flavonoids are poorly absorbed from the gastrointestinal tract. Colonic bacteria convert flavonoids into smaller phenolic acids (PA), which can be absorbed into the circulation and may contribute to the chemopreventive activity of the parent compounds. The purpose of our study was to determine whether flavonoids from green and black tea (GT, BT), citrus fruit with rutin (CF+R) and soy (S) supplements exposed to the same conditions in a dynamic in vitro model of the colon (TIM-2) will form the same phenolic acid products of microbial metabolism. About 600 mg of flavonoids from GT, BT, CF+R and S extracts were infused at t = 0 and 12 h into the TIM-2. Samples from the lumen and dialysate were collected at t = 0,4,8,12,16,24 and 28h. The flavonoid and PA concentrations were measured by HPLC and GC-MS. GT, BT, and CF+R formed 3-methoxy-4-hydroxyphenylacetic acid (3M4HPAA), 4-hydroxyphenyl acetic acid (4HPAA), 3,4-dihydroxyphenylacetic acid (3,4DHPAA), and 3-(3-hydroxyphenyl) propionic acid (3,3HPPA). BT flavonoids were also metabolized to 2,4,6-trihydroxybenzoic acid (2,4,6THBA) and CF+R flavonoids to 3-(4-hydroxy-3-methoxyphenyl) propionic acid (3,4H3MPPA), 3-hydroxyphenyl acetic acid (3HPAA) and a small amount of hippuric acid. After S infusion, we found 3M4HPAA and 4HPAA only. Among these phenolic acids, only 3,4DHPAA exhibited antiproliferative activity in prostate and colon cancer cells. 3,4DHPAA was significantly (P BT, C+R, and S flavonoids resulted in the conversion to the same major phenolic acids.

  16. Photodynamic therapy mediated antiproliferative activity of some metal-doped ZnO nanoparticles in human liver adenocarcinoma HepG2 cells under UV irradiation.

    Science.gov (United States)

    Ismail, Amel F M; Ali, Mamdouh M; Ismail, Laila F M

    2014-09-05

    Photodynamic therapy (PDT) is a promising new modality for the treatment of cancer through generation of reactive oxygen species (ROS). In this work, human liver adenocarcinoma cells HepG2 were treated with zinc oxide nanoparticles (ZnO-NPs), metal-doped-ZnO-NPs: Fe-ZnO-NPs Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs, Silica-coated ZnO-NPs, titanium dioxide nanoparticles (TiO2-NPs), titanium dioxide nano-tubes (TiO2-NTs) and ZnO-NPs/TiO2-NTs nanocomposite under UV irradiation. Doxorubicin was used as a standard drug. The results demonstrated that the ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs showed cytotoxicity against HepG2 cells, with the median growth inhibitory concentrations (IC50) 42.60, 37.20, 45.10, 77.20 and 56.50 μg/ml, respectively, as compared to doxorubicin (IC50: 20.10 μg/ml). Treatment of the cancer cells with ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs resulted in a significant increase in the activity of SOD and the levels of H2O2 and NO than those of control, accompanied with a significant decrease in the activity of CAT and GSH-Px. Also, depletion of reduced GSH, total protein and nucleic acids levels was observed. In conclusion, metal-doped ZnO-NPs may induce antiproliferative effect on HepG2 cells under UV-irradiation due to generation of ROS. Therefore, they could be included in modern clinical trials after in vivo more investigations, using photodynamic therapy technique.

  17. Osmium(III) analogues of KP1019: electrochemical and chemical synthesis, spectroscopic characterization, X-ray crystallography, hydrolytic stability, and antiproliferative activity.

    Science.gov (United States)

    Kuhn, Paul-Steffen; Büchel, Gabriel E; Jovanović, Katarina K; Filipović, Lana; Radulović, Siniša; Rapta, Peter; Arion, Vladimir B

    2014-10-20

    A one-electron reduction of osmium(IV) complexes trans-[Os(IV)Cl4(Hazole)2], where Hazole = 1H-pyrazole ([1](0)), 2H-indazole ([2](0)), 1H-imidazole ([3](0)), and 1H-benzimidazole ([4](0)), afforded a series of eight new complexes as osmium analogues of KP1019, a lead anticancer drug in clinical trials, with the general formula (cation)[trans-Os(III)Cl4(Hazole)2], where cation = H2pz(+) (H2pz[1]), H2ind(+) (H2ind[2]), H2im(+) (H2im[3]), Ph4P(+) (Ph4P[3]), nBu4N(+) (nBu4N[3]), H2bzim(+) (H2bzim[4]), Ph4P(+) (Ph4P[4]), and nBu4N(+) (nBu4N[4]). All complexes were characterized by elemental analysis, (1)H NMR spectroscopy, electrospray ionization mass spectrometry, UV-vis spectroscopy, cyclic voltammetry, while H2pz[1], H2ind[2], and nBu4[3], in addition, by X-ray diffraction. The reduced species [1](-) and [4](-) are stable in aqueous media in the absence of air oxygen and do not react with small biomolecules such as amino acids and the nucleotide 5'-dGMP. Cell culture experiments in five different human cancer cell lines (HeLa, A549, FemX, MDA-MB-453, and LS-174) and one noncancerous cell line (MRC-5) were performed, and the results were discussed and compared to those for KP1019 and cisplatin. Benzannulation in complexes with similar structure enhances antitumor activity by several orders of magnitude, implicating different mechanisms of action of the tested compounds. In particular, complexes H2ind[2] and H2bzim[4] exhibited significant antiproliferative activity in vitro when compared to H2pz[1] and H2im[3].

  18. Antiproliferative and cytotoxic activity of extracts from Cistus incanus L. and Cistus monspeliensis L. on human prostate cell lines.

    Science.gov (United States)

    Vitali, Federica; Pennisi, Giuseppa; Attaguile, Giuseppa; Savoca, Francesca; Tita, Beatrice

    2011-02-01

    Benign prostatic hypertrophy (BPH) is a common condition in elderly men that impairs quality of life and leads to a number of medical complications. The use of phytotherapeutic compounds in patients with relatively moderate BPH symptoms has been growing steadily. In the present study, acute toxicity of lyophilised aqueous extracts of Cistus incanus L. and Cistus monspeliensis L., collected in Sicily, was evaluated on the shrimp (Artemia salina L.) lethality assay, an alternative test to determine the toxicity of natural products. The cytotoxic and growth inhibitory effects were studied on normal human prostate cells (PZ-HPV-7 and PNT1A) and on a lung fibroblast cell line (V79-4). Cell proliferation was evaluated by MTT and SRB assays. Cytotoxicity was measured using the Trypan blue exclusion assay. Cistus extract treatment on prostate cell lines resulted in an almost identical growth inhibitory response and in a significant decrease in an cell viability. These findings indicate the biologically relevant effect of polyphenolic compounds present in Cistus extracts, and suggest that these substances may prove beneficial in BPH treatment.

  19. Conformational study reveals amino acid residues essential for hemagglutinating and anti-proliferative activities of Clematis montana lectin

    National Research Council Canada - National Science Library

    Bangmin Lu Bin Zhang Wei Qi Yanan Zhu Yan Zhao Nan Zhou Rong Sun Jinku Bao Chuanfang Wu

    2014-01-01

    Clematis montana lectin (CML), a novel mannose-binding lectin purified from C. montana Buch.-Ham stem (Ranunculaceae), has been proved to have hemagglutinat- ing activity in rabbit erythrocytes and apoptosis-inducing activity in tumor cells...

  20. Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Alba Montoya

    2016-07-01

    Full Text Available Twenty-four new hybrid analogues (15–38 containing 7-chloro-4-aminoquinoline and 2-pyrazoline N-heterocyclic fragments were synthesized. Twelve of the new compounds were evaluated against 58 human cancer cell lines by the U.S. National Cancer Institute (NCI. Compounds 25, 30, 31, 36, and 37 showed significant cytostatic activity, with the most outstanding GI50 values ranging from 0.05 to 0.95 µM. The hybrid compounds (15–38 were also evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. From the obtained results some structure–activity relationships were outlined.

  1. Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity.

    Science.gov (United States)

    Montoya, Alba; Quiroga, Jairo; Abonia, Rodrigo; Derita, Marcos; Sortino, Maximiliano; Ornelas, Alfredo; Zacchino, Susana; Insuasty, Braulio

    2016-07-27

    Twenty-four new hybrid analogues (15-38) containing 7-chloro-4-aminoquinoline and 2-pyrazoline N-heterocyclic fragments were synthesized. Twelve of the new compounds were evaluated against 58 human cancer cell lines by the U.S. National Cancer Institute (NCI). Compounds 25, 30, 31, 36, and 37 showed significant cytostatic activity, with the most outstanding GI50 values ranging from 0.05 to 0.95 µM. The hybrid compounds (15-38) were also evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. From the obtained results some structure-activity relationships were outlined.

  2. Iodine catalyzed one-pot synthesis of chloro-substituted linear and angular indoloquinolines and in vitro antiproliferative activity study of different indoloquinolines

    Digital Repository Service at National Institute of Oceanography (India)

    Parvatkar, P.T.; Ajay, A.K.; Bhat, M.K.; Parameswaran, P.S.; Tilve, S.G.

    ) and some indolo[2,3-b]quinolines (3a–d) against human hepatocellular carcinoma HepG2 and human breast carcinoma MCF-7 cells. Anti-proliferative assay against human hepatocellular carcinoma HepG2 and human breast carcinoma MCF-7 cells indicated methyl...

  3. Separation and isolation of tautomers of 2-hydroxy-4-naphthoquinone-1-oxime derivatives by liquid chromatography: Antiproliferative activity and DFT studies

    Indian Academy of Sciences (India)

    Yogesh Shinde; Stephen Sproules; Laxmi Kathawate; Sanjima Pal; V Badireenath Konkimalla; Sunita Salunke-Gawali

    2014-01-01

    Reversed phase HPLC separation and isolation of isomers of 2-hydroxy-4-naphthoquinone-1-oxime (Lwox) and 3-methyl-2-hydroxy-4-naphthoquinone-1-oxime (Phox) have been investigated. Two distinct peaks are observed in the chromatogram of Lwox and are assigned to `para’ tautomer; 2-hydroxy-4-naphthoquinone-1-oxime (3) and `ortho’ tautomer; 4-hydroxy-2-naphthoquinone-1-oxime (4). The tautomeric equilibrium of 3 and 4 has been manipulated by incrementally increasing the pH of the mobile phase from 2.5 to 10.5, and altering the solvent polarity. At pH > 6.8 the tautomers are well-separated from each other. There is no separation of Phox isomers between pH 2.5 and 10.5. Isolation of the tautomers has been carried out by preparative HPLC, with 3 and 4 obtained as ammonium bicarbonate adducts and characterized by LC-MS, FTIR, and UV-visible spectroscopy. Red-orange 3 is characterized by a paranaphthoquinone stretch at 1287 cm-1 and a charge transfer band at 420 nm; yellow 4 exhibits, a similar stretch at 1246 cm-1 and absorption band at 406 nm. Compounds 3 and 4 were screened for selective antiproliferative activity in three cancer cell lines of different tissue types (COLO 205 (human colorectal adenocarcinoma),U87 MG (glioblastoma astrocytoma) and MIAPaCa-2 (human pancreatic carcinoma). Geometry-optimized structures for tautomers 3 and 4 (3′ and 4′ in Phox) were computed using the B3LYP method. Structures, 3 and 3′ are 4.7 and 5.8 kcal mol-1 more stabilized than 4 and 4′, respectively, as a result of a hydrogen bond interaction between the 2-hydroxyl group and the nitrogen of the oxime.

  4. Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity

    Science.gov (United States)

    Maiorani, Orlando; Pivetta, Eliana; Capuano, Alessandra; Modica, Teresa Maria Elisa; Wassermann, Bruna; Bucciotti, Francesco; Colombatti, Alfonso; Doliana, Roberto; Spessotto, Paola

    2017-01-01

    The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context. PMID:28074935

  5. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolylpyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Directory of Open Access Journals (Sweden)

    Gerhard Kelter

    2013-03-01

    Full Text Available 2,5-bis(3′-Indolylpyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  6. Synthesis and antiproliferative activity of 2,5-bis(3'-indolyl)pyrroles, analogues of the marine alkaloid nortopsentin.

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-03-01

    2,5-bis(3'-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  7. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolyl)pyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-01-01

    2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes. PMID:23455514

  8. Trypsin Isoinhibitors with Antiproliferative Activity toward Leukemia Cells from Phaseolus vulgaris cv “White Cloud Bean”

    Directory of Open Access Journals (Sweden)

    Jian Sun

    2010-01-01

    Full Text Available A purification protocol that comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75 was complied to isolate two trypsin inhibitors from Phaseolus vulgaris cv “White Cloud Bean”. Both trypsin inhibitors exhibited a molecular mass of 16 kDa and reduced the activity of trypsin with an IC50 value of about 0.6 M. Dithiothreitol attenuated the trypsin inhibitory activity, signifying that an intact disulfide bond is indispensable to the activity. [Methyl-3H] thymidine incorporation by leukemia L1210 cells was inhibited with an IC50 value of 28.8 M and 21.5 M, respectively. They were lacking in activity toward lymphoma MBL2 cells and inhibitory effect on HIV-1 reverse transcriptase and fungal growth when tested up to 100 M.

  9. Anti-Proliferative Activity of Meroditerpenoids Isolated from the Brown Alga Stypopodium flabelliforme against Several Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Patricia Valentao

    2011-05-01

    Full Text Available The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines. Cell lines tested included human colon adenocarcinoma (Caco-2, human neuroblastoma (SH-SY5Y, rat basophilic leukemia (RBL-2H3, murine macrophages (RAW.267 and Chinese hamster fibroblasts (V79. Antimicrobial activity of the compounds was also evaluated against Staphylococcus aureus, Salmonella typhimurium, Proteus mirabilis, Bacillus cereus, Enterococcus faecalis and Micrococcus luteus. Overall, the compounds showed good activity against all cell lines, with SH-SY5Y and RAW.267 being the most susceptible. Antimicrobial capacity was observed for epitaondiol monoacetate, stypotriol triacetate and stypodiol, with the first being the most active. The results suggest that these molecules deserve further studies in order to evaluate their potential as therapeutic agents.

  10. Intention-behavior gap is wider for walking and moderate physical activity than for vigorous physical activity in university students.

    Science.gov (United States)

    Rebar, Amanda L; Maher, Jaclyn P; Doerksen, Shawna E; Elavsky, Steriani; Conroy, David E

    2016-02-01

    The theory of planned behavior proposes that physical activity is the result of intentions; however little is known about whether the relation between intentions and behavior differs between vigorous, moderate physical activity, and walking. For university students, vigorous physical activity is oftentimes enacted as a goal-directed behavior; whereas walking is oftentimes a means to achieving a goal other than physical activity (e.g., transportation). The study was a one-week prospective study. Undergraduate students (N=164) reported intentions for walking, moderate physical activity, and vigorous physical activity and self-reported these behaviors one week later. Hierarchical linear modeling revealed that intentions were more strongly related to vigorous physical activity than to moderate physical activity or walking. Intention-enhancing interventions may effectively promote vigorous physical activity, but other motivational processes may be more appropriate to target in interventions of walking and moderate physical activity. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  11. Effectiveness of a summer healthy lifestyle program for promoting moderate-vigorous activity in minority girls

    Science.gov (United States)

    Current physical activity guidelines recommend that children engage in at least 60 minutes of moderate to vigorous activity each day. However, there is little research on what types of activities are most effective for facilitating this amount of activity. To assess which physical activities elicite...

  12. Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin [Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Zheng, Shusen, E-mail: shusenzheng@zju.edu.cn [Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China)

    2015-06-05

    Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression.

  13. Synthesis and biological evaluation of indeno[1,5]naphthyridines as topoisomerase I (TopI) inhibitors with antiproliferative activity.

    Science.gov (United States)

    Alonso, Concepción; Fuertes, María; González, María; Rubiales, Gloria; Tesauro, Cinzia; Knudsen, Birgitta R; Palacios, Francisco

    2016-06-10

    In an effort to establish new candidates with improved anticancer activity, we report here the synthesis of various series of 7H-indeno[2,1-c][1,5]-naphthyridines and novel 7H-indeno[2,1-c][1,5]-naphthyridine-7-ones and 7H-indeno[2,1-c][1,5]-naphthyridine-7-ols. Most of the products which were synthesized were able to inhibit Topoisomerase I activity. Moreover, in vitro testing demonstrated that a subset of the products exhibited a cytotoxic effect on cell lines derived from human breast cancer (BT 20), human lung adenocarcinoma (A 549), or human ovarian carcinoma (SKOV3).

  14. Moderate-vigorous physical activity across body mass index in females: moderating effect of endocannabinoids and temperament.

    Science.gov (United States)

    Fernández-Aranda, Fernando; Sauchelli, Sarah; Pastor, Antoni; Gonzalez, Marcela L; de la Torre, Rafael; Granero, Roser; Jiménez-Murcia, Susana; Baños, Rosa; Botella, Cristina; Fernández-Real, Jose M; Fernández-García, Jose C; Frühbeck, Gema; Gómez-Ambrosi, Javier; Rodríguez, Roser; Tinahones, Francisco J; Arcelus, Jon; Fagundo, Ana B; Agüera, Zaida; Miró, Jordi; Casanueva, Felipe F

    2014-01-01

    Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI. Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA. Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001). Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.

  15. Moderate-vigorous physical activity across body mass index in females: moderating effect of endocannabinoids and temperament.

    Directory of Open Access Journals (Sweden)

    Fernando Fernández-Aranda

    Full Text Available Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1 examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA, temperament traits and plasma endocannabinoid concentrations; and 2 explore the association and interaction between MVPA, temperament, endocannabinoids and BMI.Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls. The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA.Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039 and high MVPA levels were associated with elevated anandamide (AEA levels (b = 0.16, p = .049 and N-oleylethanolamide (OEA levels (b = 0.22, p = .004, as well as high Novelty seeking (b = 0.18, p<.001 and low Harm avoidance (b = -0.16, p<.001.Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.

  16. The Antiproliferative and Colony-suppressive Activities of STAT3 Inhibitors in Human Cancer Cells Is Compromised Under Hypoxic Conditions.

    Science.gov (United States)

    Tian, Jilai; Xiao, Hui; Wu, Ruohan; Cao, Yang; Li, Chenglong; Xu, Ronald; Pierson, Christopher R; Finlay, Jonathan L; Yang, Fang; Gu, Ning; Lin, Jiayuh

    2017-02-01

    Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been indicated as a novel cancer drug target, since it plays an important role in diverse oncogenic processes including survival, cell proliferation and migration. Emerging STAT3 inhibitors have demonstrated efficacy in cancer cells and animal tumor models. It is well known that most solid tumors are characterized by hypoxia, but it is not clear if hypoxic conditions affect activity of STAT3 inhibitors. To examine this, two STAT3 inhibitors were tested to investigate their inhibitory efficacy in cancer cells grown under hypoxic conditions compared with those without hypoxia. Cell proliferation, colony formation and western blot assays were performed to examine the differences in the cell viability, proliferation and proteins in the STAT3 pathway. Under hypoxic conditions, the half-maximal inhibitory concentration values for both STAT3 inhibitors were increased compared to normoxic conditions in human pancreatic cancer, medulloblastoma and sarcoma cell lines. In addition, the ability of both STAT3 inhibitors to inhibit colony formation in pancreatic cancer, medulloblastoma and sarcoma cell lines was reduced under hypoxic conditions when compared to cells under normoxic conditions. Furthermore, there was an increase in phosphorylated STAT3 levels in cancer cells under hypoxic conditions, suggesting this may be one of the mechanisms of resistance. In summary, the results presented here provide a novel finding of STAT3 inhibitor activity under hypoxic conditions and indicate that under such low oxygen conditions, the anticancer efficacy of STAT3 inhibitors was indeed hampered. These results highlight the need to develop new therapeutic strategies to overcome the resistance of cancer cells to STAT3 inhibitors under hypoxic conditions.

  17. Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities

    OpenAIRE

    Tzanetou, Evangelia; Liekens, Sandra; Kasiotis, Konstantinos M.; Fokialakis, Nikolas; Haroutounian, Serkos A

    2012-01-01

    The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values o...

  18. Evaluation of antiproliferative and anti-inflammatory activities of methanol extract and its fractions from the Mediterranean sponge

    OpenAIRE

    2012-01-01

    Abstract Background Without doubt, natural products have been, and still are, the cornerstone of the health care armamentarium. Of all natural sources, the marine environment is clearly the last great frontier for pharmaceutical and medical research. Methods This work progresses in the direction of identifying component(s) from the Mediterranean sponge, Spongia officinalis with pharmacological activities. In the present study we investigated the efficacy of methanol extract and its semi-purif...

  19. 2-Benzazolyl-4-Piperazin-1-Ylsulfonylbenzenecarbohydroxamic Acids as Novel Selective Histone Deacetylase-6 Inhibitors with Antiproliferative Activity.

    Science.gov (United States)

    Wang, Lei; Kofler, Marina; Brosch, Gerald; Melesina, Jelena; Sippl, Wolfgang; Martinez, Elisabeth D; Easmon, Johnny

    2015-01-01

    We have screened our compound collection in an established cell based assay that measures the derepression of an epigenetically silenced transgene, the locus derepression assay. The screen led to the identification of 4-[4-(1-methylbenzimidazol-2-yl)piperazin-1-yl]sulfonylbenzenecarbohydroxamic acid (9b) as an active which was found to inhibit HDAC1. In initial structure activity relationships study, the 1-methylbenzimidazole ring was replaced by the isosteric heterocycles benzimidazole, benzoxazole, and benzothiazole and the position of the hydroxamic acid substituent on the phenyl ring was varied. Whereas compounds bearing a para substituted hydroxamic acid (9a-d) were active HDAC inhibitors, the meta substituted analogues (8a-d) were appreciably inactive. Compounds 9a-d selectively inhibited HDAC6 (IC50 = 0.1-1.0 μM) over HDAC1 (IC50 = 0.9-6 μM) and moreover, also selectively inhibited the growth of lung cancer cells vs. patient matched normal cells. The compounds induce a cell cycle arrest in the S-phase while induction of apoptosis is neglible as compared to controls. Molecular modeling studies uncovered that the MM-GBSA energy for interaction of 9a-d with HDAC6 was higher than for HDAC1 providing structural rationale for the HDAC6 selectivity.

  20. Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells.

    Science.gov (United States)

    Li, Miao; Liu, Qin; Cui, Yajuan; Li, Dong; Wang, Hexiang; Ng, Tzi Bun

    2017-01-23

    A 17.5-kDa trypsin inhibitor was purified from Phaseolus vulgaris cv. "gold bean" with an isolation protocol including ion exchange chromatography on DEAE-cellulose (Diethylaminoethyl-cellulose), affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-sepharose (Sulfopropyl-sepharose), and gel filtration by FPLC (Fast protein liquid chromatography) on Superdex 75. It dose-dependently inhibited trypsin with an IC50 value of 0.4 μM, and this activity was reduced in the presence of dithiothreitol in a dose- and time-dependent manner, signifying the importance of the disulfide linkage to the activity. It inhibited [methyl-³H] thymidine incorporation by leukemia L1210 cells and lymphoma MBL2 cells with an IC50 value of 2.3 μM and 2.5 μM, respectively. The inhibitor had no effect on fungal growth and the activities of various viral enzymes when tested up to 100 μM.

  1. Isolation and characterization of a Kunitz-type trypsin inhibitor with antiproliferative activity from Gymnocladus chinensis (Yunnan bean) seeds.

    Science.gov (United States)

    Zhu, M J; Zhang, G Q; Wang, H X; Ng, T B

    2011-04-01

    A 20-kDa Kunitz-type trypsin inhibitor was isolated from Gymnocladus chinensis (Yunnan bean) seeds. The isolation procedure involved ion exchange chromatography on diethylaminoethyl cellulose (DEAE-cellulose), affinity chromatography on Affi-gel blue gel, ion exchange chromatography on sulfopropyl sepharose (SP-sepharose), and gel filtration by FPLC on Superdex 75. The trypsin inhibitor was adsorbed on DEAE-cellulose, unadsorbed on Affi-gel blue gel, and adsorbed on SP-Sepharose. It dose-dependently inhibited trypsin with an IC(50) value of 0.4 μM. Dithiothreitol reduced its trypsin inhibitory activity, suggesting that an intact disulfide bond is indispensable to the activity. It suppressed [methyl-(3)H] thymidine incorporation by leukemia L1210 cells and lymphoma MBL2 cells with an IC(50) value of 4.7 and 9.4 μM, respectively. There was no effect on human immunodeficiency virus(4)-1 reverse transcriptase activity and fungal growth when the trypsin inhibitor was tested up to 100 μM.

  2. Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Miao Li

    2017-01-01

    Full Text Available A 17.5-kDa trypsin inhibitor was purified from Phaseolus vulgaris cv. “gold bean” with an isolation protocol including ion exchange chromatography on DEAE-cellulose (Diethylaminoethyl-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-sepharose (Sulfopropyl-sepharose, and gel filtration by FPLC (Fast protein liquid chromatography on Superdex 75. It dose-dependently inhibited trypsin with an IC50 value of 0.4 μM, and this activity was reduced in the presence of dithiothreitol in a dose- and time-dependent manner, signifying the importance of the disulfide linkage to the activity. It inhibited [methyl-3H] thymidine incorporation by leukemia L1210 cells and lymphoma MBL2 cells with an IC50 value of 2.3 μM and 2.5 μM, respectively. The inhibitor had no effect on fungal growth and the activities of various viral enzymes when tested up to 100 μM.

  3. 2-Benzazolyl-4-Piperazin-1-Ylsulfonylbenzenecarbohydroxamic Acids as Novel Selective Histone Deacetylase-6 Inhibitors with Antiproliferative Activity

    Science.gov (United States)

    Wang, Lei; Kofler, Marina; Brosch, Gerald; Melesina, Jelena; Sippl, Wolfgang; Martinez, Elisabeth D.; Easmon, Johnny

    2015-01-01

    We have screened our compound collection in an established cell based assay that measures the derepression of an epigenetically silenced transgene, the locus derepression assay. The screen led to the identification of 4-[4-(1-methylbenzimidazol-2-yl)piperazin-1-yl]sulfonylbenzenecarbohydroxamic acid (9b) as an active which was found to inhibit HDAC1. In initial structure activity relationships study, the 1-methylbenzimidazole ring was replaced by the isosteric heterocycles benzimidazole, benzoxazole, and benzothiazole and the position of the hydroxamic acid substituent on the phenyl ring was varied. Whereas compounds bearing a para substituted hydroxamic acid (9a-d) were active HDAC inhibitors, the meta substituted analogues (8a-d) were appreciably inactive. Compounds 9a-d selectively inhibited HDAC6 (IC50 = 0.1–1.0μM) over HDAC1 (IC50 = 0.9–6μM) and moreover, also selectively inhibited the growth of lung cancer cells vs. patient matched normal cells. The compounds induce a cell cycle arrest in the S-phase while induction of apoptosis is neglible as compared to controls. Molecular modeling studies uncovered that the MM-GBSA energy for interaction of 9a-d with HDAC6 was higher than for HDAC1 providing structural rationale for the HDAC6 selectivity. PMID:26698121

  4. 2-Benzazolyl-4-Piperazin-1-Ylsulfonylbenzenecarbohydroxamic Acids as Novel Selective Histone Deacetylase-6 Inhibitors with Antiproliferative Activity.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available We have screened our compound collection in an established cell based assay that measures the derepression of an epigenetically silenced transgene, the locus derepression assay. The screen led to the identification of 4-[4-(1-methylbenzimidazol-2-ylpiperazin-1-yl]sulfonylbenzenecarbohydroxamic acid (9b as an active which was found to inhibit HDAC1. In initial structure activity relationships study, the 1-methylbenzimidazole ring was replaced by the isosteric heterocycles benzimidazole, benzoxazole, and benzothiazole and the position of the hydroxamic acid substituent on the phenyl ring was varied. Whereas compounds bearing a para substituted hydroxamic acid (9a-d were active HDAC inhibitors, the meta substituted analogues (8a-d were appreciably inactive. Compounds 9a-d selectively inhibited HDAC6 (IC50 = 0.1-1.0 μM over HDAC1 (IC50 = 0.9-6 μM and moreover, also selectively inhibited the growth of lung cancer cells vs. patient matched normal cells. The compounds induce a cell cycle arrest in the S-phase while induction of apoptosis is neglible as compared to controls. Molecular modeling studies uncovered that the MM-GBSA energy for interaction of 9a-d with HDAC6 was higher than for HDAC1 providing structural rationale for the HDAC6 selectivity.

  5. Synthesis, antiproliferative activity and DNA binding properties of novel 5-aminobenzimidazo[1,2-a]quinoline-6-carbonitriles.

    Science.gov (United States)

    Perin, Nataša; Nhili, Raja; Ester, Katja; Laine, William; Karminski-Zamola, Grace; Kralj, Marijeta; David-Cordonnier, Marie-Hélène; Hranjec, Marijana

    2014-06-10

    The synthesis of 5-amino substituted benzimidazo[1,2-a]quinolines prepared by microwave assisted amination from halogeno substituted precursor was described. The majority of compounds were active at micromolar concentrations against colon, lung and breast carcinoma cell lines in vitro. The N,N-dimethylaminopropyl 9 and piperazinyl substituted derivative 19 showed the most pronounced activity towards all of the three tested tumor cell lines, which could be correlated to the presence of another N heteroatom and its potential interactions with biological targets. The DNA binding studies, consisting of UV/Visible absorbency, melting temperature studies, and fluorescence and circular dichroism titrations, revealed that compounds 9, 19 and 20 bind to DNA as strong intercalators. The cellular distribution analysis, based on compounds' intrinsic fluorescence, showed that compound 20 does not enter the cell, while compounds 9 and 19 do, which is in agreement with their cytotoxic effects. Compound 9 efficiently targets the nucleus whereas 19, which also showed DNA intercalating properties in vitro, was mostly localised in the cytoplasm suggesting that the antitumor mechanism of action is DNA-independent. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Anti-Proliferative Activity of λ-Carrageenan Through the Induction of Apoptosis in Human Breast Cancer Cells

    Science.gov (United States)

    Jazzara, Marie; Ghannam, Ahmed; Soukkarieh, Chadi; Murad, Hossam

    2016-01-01

    Background Sulfated Polysaccharides (SPs) possess spectrum of pharmacological and therapeutic properties that could attributed to their origins variation, chemical structures and biological activities. Various studies have shown the impact of SPs on proliferation in different cancer cell lines. Objectives In this study, we have evaluated the biological effects of λ-carrageenan, a highly SP, extracted from the red seaweed Laurencia papillosa, on MDA-MB-231 cancer cell line. Materials and Methods MDA-MB-231 cells have treated with λ-carrageenan, the viability and apoptosis have assessed by the appropriate florescent probes on flow cytometer. The expression levels of mRNA of apoptotic genes have detected by real-time PCR analysis. Results Our results have indicated that the signaling pathway of λ-carrageenan inhibited the proliferation of MDA-MB-231 cells by up-regulating the pro-apoptotic genes caspase-8, caspase-9, caspase-3 which have been resulting the increased levels of active caspase-3 protein. Furthermore, This SP had that capacity to disrupt the mitochondrial function by altering the bax/bcl-2 ratio of expression which has considered an important element in apoptosis induction. Conclusions The presented results have signposted that λ-carrageenan was a promising bioactive polymer which could be a potential candidate in preventing or treating breast cancer. PMID:27761203

  7. Antitumor activity of orally bioavailable farnesyltransferase inhibitor, ABT-100, is mediated by antiproliferative, proapoptotic, and antiangiogenic effects in xenograft models.

    Science.gov (United States)

    Ferguson, Debra; Rodriguez, Luis E; Palma, Joann P; Refici, Marion; Jarvis, Kenneth; O'Connor, Jacqueline; Sullivan, Gerard M; Frost, David; Marsh, Kennan; Bauch, Joy; Zhang, Haiying; Lin, Nan-Horng; Rosenberg, Saul; Sham, Hing L; Joseph, Ingrid B J K

    2005-04-15

    To evaluate the preclinical pharmacokinetics, antitumor efficacy, and mechanism of action of a novel orally active farnesyltransferase inhibitor, ABT-100. In vitro sensitivity of a panel of human cell lines was determined using proliferation and clonogenic assays. In vivo efficacy of ABT-100 was evaluated in xenograft models (flank or orthotopic) by assessing angiogenesis, proliferation, and apoptosis in correlation with pharmacokinetics. Efficacy of the racemate of ABT-100 (A-367074) was also compared with R115777 (tipifarnib). ABT-100 inhibited proliferation of cells in vitro carrying oncogenic H-Ras (EJ-1 bladder; IC(50) 2.2 nmol/L), Ki-Ras (DLD-1 colon, MDA-MB-231 breast, HCT-116 colon, and MiaPaCa-2 pancreatic; IC(50) range, 3.8-9.2 nmol/L), and wild-type Ras (PC-3 and DU-145; IC(50), 70 and 818 nmol/L, respectively) as well as clonogenic potential. ABT-100 shows 70% to 80% oral bioavailability in mice. ABT-100 regressed EJ-1 tumors (2-12.5 mg/kg/d s.c., every day for 21 days) and showed significant efficacy in DLD-1, LX-1, MiaPaCa-2, or PC-3 tumor-bearing mice (6.25-50 mg/kg/d s.c. once daily or twice daily orally). A-367074 showed equivalent efficacy to R115777 given at approximately one-fourth the total dose of R115777 for a shorter duration (EJ-1 and LX-1). Antitumor activity was associated with decreased cell proliferation (Ki-67), increased apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling), and decreased angiogenesis. A reduction in tumor angiogenic cytokine levels (vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8) correlated with a reduction in tumor vascularity (CD31). Overall, ABT-100 has an acceptable pharmacokinetic profile, is well tolerated, and possesses broad-spectrum antitumor activity against a series of xenograft models similar to farnesyltransferase inhibitors in clinical development; therefore, it is an attractive candidate for clinical evaluation.

  8. Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities.

    Science.gov (United States)

    Tzanetou, Evangelia; Liekens, Sandra; Kasiotis, Konstantinos M; Fokialakis, Nikolas; Haroutounian, Serkos A

    2012-10-01

    The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values of 1.5 ± 0.4 µM and 5.6 ± 2.5 µM, respectively, against MCF-7 cells. In addition, the indazole derivative 16 was assessed as a competent inhibitor of endothelial tube formation at 30 µM.

  9. Chemical profile, antiproliferative and antioxidant activities of rhizome oil of Zingiber anamalayanum from Western Ghats in India.

    Science.gov (United States)

    Salim, Mohamed; Kabeer, T K Ahmedul; Nair, S Ajikumaran; Dan, Mathew; Sabu, M; Baby, Sabulal

    2016-09-01

    Volatile oil from fresh rhizomes of Zingiber anamalayanum was isolated by hydrodistillation and characterised by GC-FID and GC-MS. Twenty-one out of 24 constituents comprising 99.47% of the oil were identified. Major components in Z. anamalayanum rhizome oil were δ-2-carene (52.83%), camphene (9.83%), endo-fenchol (9.42%), iso-dihydrocarveol (6.44%) and cis-p-mentha-2,8-dien-1-ol (5.19%). Monoterpene hydrocarbons in the rhizome oil were 65.81%, followed by oxygenated monoterpenes (23.78%) and sesquiterpene hydrocarbons (9.87%). Physical parameters of rhizome oil were [Formula: see text] 1.4031, [Formula: see text] - 16.097(o) (c = 1, CHCl3) and [Formula: see text] 0.9202. Z. anamalayanum rhizome oil showed significant anti-Dalton's Lymphoma Ascitic activity.

  10. Reactivity and antiproliferative activity of ferrocenyl-tamoxifen adducts with cyclodextrins against hormone-independent breast-cancer cell lines.

    Science.gov (United States)

    Buriez, Olivier; Heldt, Jan Martin; Labbé, Eric; Vessières, Anne; Jaouen, Gerard; Amatore, Christian

    2008-01-01

    Hydroxyferrocifen compounds are a new and promising class of ferrocifen-type breast-cancer drug candidates. They possess both endocrine-modulating properties and cytotoxic activity, which come from the tamoxifen skeleton and the presence of a ferrocene moiety, respectively. However, they suffer from reduced solubility in water, which presents a problem for their eventual therapeutic use. Herein, we examined the interactions of hydroxyferrocifen compounds with cyclodextrins (CDs) to evaluate whether or not their electron-transfer oxidation pathways were affected by their inclusion. It has been demonstrated that these inclusion complexes are soluble in pure water, which shows that CDs can be used to deliver these biologically active molecules. Therefore, a series of these compounds has been investigated by cyclic voltametry in various media in the presence of CDs (beta-CD and Me-beta-CD). In methanol, the hydroxyferrocifen compounds exhibited a weak interaction with the CD cavity. These interactions became stronger as the amount of added water increased. The complexation effect between the hydroxyferrocifen compounds and beta-CD was found to be stronger if the CD was partially methylated, which is probably due to hydrophobic effects between the cyclopentadienyl ring and/or the aromatic rings and the methoxy groups. Moreover, it appears that the structure of the hydroxyferrocifen compounds affects both their solubility and their complexation dynamics. Investigations in the presence of pyridine show that the base kinetically favors the dissociation of the ferrocifen-CD complex during the electron transfer step, but does not affect the follow-up reactivity of the electrogenerated ferrocenium cation, which leads eventually to the corresponding quinone methide, as reported in the absence of CD. Accordingly, the cytotoxicity of these beta-CD-encapsulated organometallic complexes in hormone-independent breast-cancer cells (MDA-MB231) were confirmed to be similar to those

  11. Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells.

    Science.gov (United States)

    Lee, Yoo Jin; Cui, Jun; Lee, Jun; Han, Ah-Reum; Lee, Eun Byul; Jang, Ho Hee; Seo, Eun Kyoung

    2016-01-01

    Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3-17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1-17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer.

  12. Behavioral Activation for Moderately Depressed University Students: Randomized Controlled Trial

    Science.gov (United States)

    Gawrysiak, Michael; Nicholas, Christopher; Hopko, Derek R.

    2009-01-01

    Although depression is prevalent among university students, limited and dated research has examined the efficacy of behavioral interventions in treating this population (C. Lee, 2005). On the basis of a modified version of the Behavioral Activation Treatment for Depression (BATD; D. R. Hopko & C. W. Lejuez, 2007; C. W. Lejuez, D. R. Hopko, & S. D.…

  13. Promoting Moderate-Vigorous Physical Activity in Overweight Minority Girls

    Directory of Open Access Journals (Sweden)

    Norma Olvera

    2010-01-01

    Full Text Available There is limited research on the types of activities that are most effective for promoting MVPA in children. Purpose. To assess which types of activities elicit MVPA in overweight minority girls. Methods. Sample consisted of 31 overweight (BMI≥85th percentile Latina and African-American girls (mean age 10.3±1.2 years. Participants wore an Actical accelerometer each day for 8 hours for 15 days to assess engagement in MVPA during their participation in a three-week activity intervention that included traditional fitness, sport skills, games, dancing, and flexibility sessions. Results. On average 62% of participants met the MVPA recommended guidelines (60 min/5d/wk with an average of 68.5±14 minutes of MVPA across the three weeks. Traditional fitness sessions elicited the highest percent of MVPA (mean time spent in MVPA=32%, followed by dancing and games (mean time spent in MVPA=21%, sports skills (mean time spent in MVPA=18%, and flexibility (mean time spent in MVPA=7%. Step aerobics and rumba fitness elicited the highest proportions of MVPA. Conclusion. Traditional fitness activities were identified as the most successful in eliciting MVPA in overweight Latina and African American girls.

  14. Promoting moderate-vigorous physical activity in overweight minority girls.

    Science.gov (United States)

    Olvera, Norma; Graham, Marilynn; McLeod, Jessica; Kellam, Stephanie F; Butte, Nancy F

    2010-01-01

    There is limited research on the types of activities that are most effective for promoting MVPA in children. Purpose. To assess which types of activities elicit MVPA in overweight minority girls. Methods. Sample consisted of 31 overweight (BMI >/= 85th percentile) Latina and African-American girls (mean age 10.3 +/- 1.2 years). Participants wore an Actical accelerometer each day for 8 hours for 15 days to assess engagement in MVPA during their participation in a three-week activity intervention that included traditional fitness, sport skills, games, dancing, and flexibility sessions. Results. On average 62% of participants met the MVPA recommended guidelines (60 min/5d/wk) with an average of 68.5 +/- 14 minutes of MVPA across the three weeks. Traditional fitness sessions elicited the highest percent of MVPA (mean time spent in MVPA = 32%), followed by dancing and games (mean time spent in MVPA = 21%), sports skills (mean time spent in MVPA = 18%), and flexibility (mean time spent in MVPA = 7%). Step aerobics and rumba fitness elicited the highest proportions of MVPA. Conclusion. Traditional fitness activities were identified as the most successful in eliciting MVPA in overweight Latina and African American girls.

  15. Active Reading Procedures for Moderating the Effects of Poor Highlighting

    Science.gov (United States)

    Gier, Vicki S.; Herring, Daniel; Hudnell, Jason; Montoya, Jodi; Kreiner, David S.

    2010-01-01

    We investigated two active reading techniques intended to eliminate the negative effect on reading comprehension of preexisting, inappropriate highlighting. College students read passages in three highlighting conditions: no highlighting, appropriate highlighting, and inappropriate highlighting. In Experiment 1, 30 students read the passages while…

  16. A novel alkaline protease with antiproliferative activity from fresh fruiting bodies of the toxic wild mushroom Amanita farinosa.

    Science.gov (United States)

    Sun, Jian; Zhao, Yongchang; Chai, Hongmei; Wang, Hexiang; Ng, Tzi Bun

    2011-01-01

    A novel protease with a molecular mass of 15 kDa was purified from fresh fruiting bodies of the wild mushroom Amanita farinosa. The purification protocol entailed anion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, cation exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The protease was unadsorbed on DEAE-cellulose but adsorbed on Affi-gel blue gel and SP-Sepharose. It demonstrated a single 15-kDa band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS/PAGE) and a 15-kDa peak in gel filtration. The optimal pH and optimal temperature of the protease were pH 8.0 and 65 °C, respectively. Proliferation of human hepatoma HepG2 cells was inhibited by the protease with an IC(50) of 25 µM. The protease did not have antifungal or ribonuclease activity.

  17. Isolation and characterization of an antifungal peptide with antiproliferative activity from seeds of Phaseolus vulgaris cv. 'Spotted Bean'.

    Science.gov (United States)

    Wang, H X; Ng, T B

    2007-02-01

    A 7.3-kDa antifungal peptide with an N-terminal sequence exhibiting remarkable homology to defensins from other leguminous plants was isolated from Phaseolus vulgaris cv. 'Spotted Bean'. The isolation procedure involved ion exchange chromatography on O-diethylaminoethyl (DEAE) cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The peptide was unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and SP-Sepharose. It exerted an antifungal action on Fusarium oxysporum and Mycosphaerella arachidicola. It inhibited mycelial growth in F. oxysporum with an IC(50) value of 1.8 microM. It suppressed [methyl-(3)H]-thymidine incorporation by leukemia L1210 cells and MBL2 cells with an IC(50) value of 4.0 and 9.0 microM, respectively. There was no effect on HIV-1 reverse transcriptase activity when the peptide was tested up to 0.1 mM.

  18. Two New Oleanane-Type Saponins with Anti-Proliferative Activity from Camellia oleifera Abel. Seed Cake

    Directory of Open Access Journals (Sweden)

    Jian-Fa Zong

    2016-02-01

    Full Text Available Two new oleanane-type saponins, named oleiferasaponins C4 (1 and C5 (2, were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galacto-pyranosyl-(1→2]-[β-d-glucopyranosyl-(1→2-β-d-galactopyranosy-(1→3]-β-d-glucopyranosid-uronic acid methyl ester (1 and 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxy-methylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2]-[β-d-galactopyranosyl-(1→3]-β-d-glucopyranosiduronic acid methyl ester (2 through 1D- and 2D-NMR, HR-ESI-MS, and GC-MS spectroscopic methods. The two compounds exhibited potent cytotoxic activities against five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB.

  19. Antiproliferative activity of the dietary isothiocyanate erucin, a bioactive compound from cruciferous vegetables, on human prostate cancer cells.

    Science.gov (United States)

    Melchini, Antonietta; Traka, Maria H; Catania, Stefania; Miceli, Natalizia; Taviano, Maria Fernanda; Maimone, Patrizia; Francisco, Marta; Mithen, Richard F; Costa, Chiara

    2013-01-01

    It is becoming increasingly clear that many dietary agents, such as isothiocyanates (ITCs) from cruciferous vegetables, can retard or prevent the process of prostate carcinogenesis. Erucin (ER) is a dietary ITC, which has been recently considered a promising cancer chemopreventive phytochemical. The potential protective activity of ER against prostate cancer was investigated using prostate adenocarcinoma cells (PC3), to analyze its effects on pathways involved in cell growth regulation, such as the cyclin-dependent kinase (CDKs) inhibitor p21(WAF1/CIP1) (p21), phosphatidylinositol-3 kinase/AKT, and extracellular signal-regulated kinases (ERK)1/2 signaling pathways. We have shown for the first time that ER increases significantly p21 protein expression and ERK1/2 phosphorylation in a dose-dependent manner to inhibit PC3 cell proliferation (P ≤ 0.01). Compared to the structurally related sulforaphane, a well-studied broccoli-derived ITC, ER showed lower potency in inhibiting proliferation of PC3 cells, as well as in modulating p21 and pERK1/2 protein levels. Neither of the naturally occurring ITCs was able to affect significantly pAKT protein levels in prostate cells at all concentrations tested (0-25 μM). It is clearly important for the translation of laboratory findings to clinical approaches to investigate in animal and cell studies the molecular mechanisms by which ITCs may exert health promoting effects.

  20. Applying the Theory of Planned Behavior to Physical Activity: The Moderating Role of Mental Toughness.

    Science.gov (United States)

    Hannan, Thomas E; Moffitt, Robyn L; Neumann, David L; Thomas, Patrick R

    2015-10-01

    This study explored whether mental toughness, the capacity to maintain performance under pressure, moderated the relation between physical activity intentions and subsequent behavior. Participants (N = 117) completed the Mental Toughness Index and a theory of planned behavior questionnaire. Seven days later, physical activity was assessed using the International Physical Activity Questionnaire. Attitudes, subjective norms, and perceived behavioral control explained substantial variance (63.1%) in physical activity intentions. Intentions also significantly predicted physical activity behavior. The simple slopes analyses for the moderation effect revealed a nonsignificant intention-behavior relation at low levels of mental toughness. However, intentions were significantly and positively related to physical activity when mental toughness was moderate or high, suggesting that the development of a mentally tough mindset may reduce the gap between behavior and physical activity intention. Future research is needed to confirm these findings and apply them in the design of mental toughness interventions to facilitate physical activity engagement.

  1. Retinoblastoma-independent antiproliferative activity of novel intracellular antibodies against the E7 oncoprotein in HPV 16-positive cells

    Directory of Open Access Journals (Sweden)

    Banks Lawrence

    2011-01-01

    Full Text Available Abstract Background "High risk" Human Papillomavirus strains are the causative agents of the vast majority of carcinomas of the uterine cervix. In these tumors, the physical integration of the HPV genome is a frequent, though not invariable occurrence, but the constitutive expression of the E6 and E7 viral genes is always observed, suggesting key roles for the E6 and E7 oncoproteins in the process of malignant transformation. The "intracellular antibody" technology using recombinant antibodies in single-chain format offers the possibility of targeting a protein in its intracellular environment even at the level of definite domains thus representing a valuable strategy to "knock out" the function of specific proteins. Methods In this study, we investigate the in vitro activity of two single-chain antibody fragments directed against the "high-risk" HPV 16 E7 oncoprotein, scFv 43M2 and scFv 51. These scFvs were expressed by retroviral system in different cell compartments of the HPV16-positive SiHa cells, and cell proliferation was analyzed by Colony Formation Assay and EZ4U assay. The binding of these scFvs to E7, and their possible interference with the interaction between E7 and its main target, the tumor suppressor pRb protein, were then investigated by immunoassays, PepSet™technology and Surface Plasmon Resonance. Results The expression of the two scFvs in the nucleus and the endoplasmic reticulum of SiHa cells resulted in the selective growth inhibition of these cells. Analysis of binding showed that both scFvs bind E7 via distinct but overlapping epitopes not corresponding to the pRb binding site. Nevertheless, the binding of scFv 43M2 to E7 was inhibited by pRb in a non-competitive manner. Conclusions Based on the overall results, the observed inhibition of HPV-positive SiHa cells proliferation could be ascribed to an interaction between scFv and E7, involving non-pRb targets. The study paves the way for the employment of specific sc

  2. Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex.

    Science.gov (United States)

    Rossi, D; Bruni, R; Bianchi, N; Chiarabelli, C; Gambari, R; Medici, A; Lista, A; Paganetto, G

    2003-03-01

    Sangre de Drago is a red viscous latex extracted from Croton lechleri (Euphorbiaceae) cortex, renowned in South American popular medicine for its wound-healing properties. The in vitro antiproliferative effects were determined on the human myelogenous leukemia K562 cells line (IC50 = 2.5 +/- 0.3 microg ml(-1)). The mutagenic and antimutagenic activity of C. lechleri sap was examined by means of the Ames/Salmonella test. No mutagenic activity was found on the Salmonella typhimurium strains T98 and T100, either with or without S9 activation. On the other hand, the sap showed an inhibitory effect against the mutagenic activity of the indirectly acting mutagen 2-Aminoanthracene in presence of S9 and a moderate protective activity against directly acting mutagens Sodium Azide and 2-Nitrofluorene. Therefore we suggest that C. lechleri sap interacts with the enzymes of the S9 mix, thereby inhibiting the transformation of 2-Aminoantracene into its active forms.

  3. Correlates of physical activity among young children with moderate acute malnutrition

    DEFF Research Database (Denmark)

    Yaméogo, Charles W; Cichon, Bernardette; Fabiansen, Christian

    2017-01-01

    OBJECTIVE: To assess the levels of physical activity among young children with moderate acute malnutrition and to identify clinical, biochemical, anthropometric, and sociodemographic correlates of physical activity. STUDY DESIGN: In a cross-sectional study, 1609 children aged 6-23 months wore......) cpm lower activity, respectively. Elevated serum C-reactive protein and α1-acid glycoprotein were both negative correlates of physical activity, and hemoglobin was a positive correlate. CONCLUSIONS: Physical activity declines with age in children with moderate acute malnutrition and is also inversely...

  4. Conscientiousness, extroversion, and action control: comparing moderate and vigorous physical activity.

    Science.gov (United States)

    de Bruijn, Gert-Jan; de Groot, Ruben; van den Putte, Bas; Rhodes, Ryan

    2009-12-01

    The present study explored the influence of the Big Five dimensions extroversion and conscientiousness on action control regarding both moderate and vigorous physical activity within the framework of the theory of planned behavior (TPB). Prospective data were available from 186 respondents, who completed measures of intention, cognitive and affective attitude, subjective norm, perceived behavioral control, extroversion, conscientiousness, and physical activity at T1. Four weeks later, physical activity was assessed again. Respondents were grouped into four profiles: nonintenders, successful nonintenders, unsuccessful intenders, and successful intenders. Logistic regression analyses revealed that successful enactment in moderate physical activity was associated with extroversion, subjective norm, and affective attitude, whereas successful enactment in vigorous physical activity was associated with conscientiousness. Findings illustrate the differential role played by personality dimensions and TPB concepts in the explanation of moderate and vigorous physical activity action control.

  5. Antiproliferative Activity of Fucan Nanogel

    OpenAIRE

    Francisco Miguel Gama; Hugo Alexandre Oliveira Rocha; Paula Pereira; Silvia Santos Pedrosa; Arthur Anthunes Jacome Vidal; Ruth Medeiros Oliveira; Dayanne Lopes Gomes; Jailma Almeida-Lima; Nednaldo Dantas-Santos

    2012-01-01

    Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated l-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc) formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by e...

  6. Moderate physical activity and breast cancer risk: the effect of menopausal status.

    Science.gov (United States)

    Angeles-Llerenas, Angélica; Ortega-Olvera, Carolina; Pérez-Rodríguez, Edelmiro; Esparza-Cano, Jesús Pablo; Lazcano-Ponce, Eduardo; Romieu, Isabelle; Torres-Mejía, Gabriela

    2010-04-01

    It has been suggested that both moderate-and vigorous-intensity physical activity reduces the risk of breast cancer. However, the effect of moderate-intensity physical activity on breast cancer risk has not been consistently evaluated by menopausal status and has not been evaluated in Mexican women. To evaluate the effect of moderate-intensity physical activity (h/week and MET-h/week) on the risk of breast cancer by menopausal status in Mexican women. A population-based case-control study was conducted in Mexico. One thousand incident cases and 1,074 matched controls to cases by 5 years of age, site and health institution participated in the study. Women provided information on health, diet and physical activity by means of an in-person interview. Anthropometric measurements and blood samples were obtained from all women. A conditional logistic regression model was used to assess this association. Participating in moderate-intensity physical activity decreased the risk of BC in both pre- and postmenopausal women (OR = 0.96; 95% CI 0.92.-0.99; OR = 0.90; 95% CI 0.86-0.93, respectively) for every 3 h per week of moderate-intensity physical activity. There was a statistically significant modification effect by menopausal status (p = 0.009). Strategies need to be identified that will engage women in physical activity programs.

  7. New geranylated flavanones from the fruits of Paulownia catalpifolia Gong Tong with their anti-proliferative activity on lung cancer cells A549.

    Science.gov (United States)

    Gao, Tian-yang; Jin, Xing; Tang, Wen-zhao; Wang, Xiao-jing; Zhao, Yun-xue

    2015-09-01

    Three new geranylated flavanones, named as paucatalinone A (1), B (2), and isopaucatalinone B (3), were isolated from the fruits of Paulownia catalpifolia Gong Tong (Scrophulariaceae). Their structures were well determined by means of IR, MS, 1D and 2D NMR, and CD techniques. Paucatalinone A (1) is the first sample as a dimeric geranylated flavanone derivative isolated from natural products. Paucatalinone A (1) displayed good antiproliferative effects on human lung cancer cells A549 and resulted in a clear increase of the percentage of cells in G1 phase and a decrease in the percentage of cells in S and G2/M phases in comparison with control cells.

  8. Moderators of the Relationship between Physical Activity and Alcohol Consumption in College Students

    Science.gov (United States)

    Buscemi, Joanna; Martens, Matthew P.; Murphy, James G.; Yurasek, Ali M.; Smith, Ashley E.

    2011-01-01

    Objective: Among college students, several studies have found a positive relationship between physical activity and alcohol use. The current study tested gender, Greek status, and ethnicity as potential moderators of the physical activity-alcohol use relationship. Participants: Participants were college freshmen (n = 310) endorsing alcohol/drug…

  9. Metabolic syndrome risk score and time expended in moderate to vigorous physical activity in adolescents

    OpenAIRE

    Stabelini Neto,Antonio; Campos,Wagner de; dos Santos, Géssika Castilho; Mazzardo Junior, Oldemar

    2014-01-01

    Background The clustering of metabolic syndrome risk factors is inversely related to the amount of physical activity. However, the question remains as to how much daily physical activity is enough to prevent the onset of metabolic disorders in adolescents? Therefore, the objectives of this study were to associate the metabolic risk score with the moderate to vigorous physical activity (MVPA) and to identify the amount of daily physical activity to prevent the onset of the metabolic risk facto...

  10. A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands.

    Science.gov (United States)

    Crowe, David L; Chandraratna, Roshantha A S

    2004-01-01

    Certain lipids have been shown to be ligands for a subgroup of the nuclear hormone receptor superfamily known as the peroxisome proliferator-activated receptors (PPARs). Ligands for these transcription factors have been used in experimental cancer therapies. PPARs heterodimerize and bind DNA with retinoid X receptors (RXRs), which have homology to other members of the nuclear receptor superfamily. Retinoids have been found to be effective in treating many types of cancer. However, many breast cancers become resistant to the chemotherapeutic effects of these drugs. Recently, RXR-selective ligands were discovered that inhibited proliferation of all-trans retinoic acid resistant breast cancer cells in vitro and caused regression of the disease in animal models. There are few published studies on the efficacy of combined therapy using PPAR and RXR ligands for breast cancer prevention or treatment. We determined the effects of selective PPAR and RXR ligands on established human breast cancer cell lines in vitro. PPAR-alpha and PPAR-gamma ligands induced apoptotic and antiproliferative responses in human breast cancer cell lines, respectively, which were associated with specific changes in gene expression. These responses were potentiated by the RXR-selective ligand AGN194204. Interestingly, RXR-alpha-overexpressing retinoic acid resistant breast cancer cell lines were more sensitive to the effects of the RXR-selective compound. RXR-selective retinoids can potentiate the antiproliferative and apoptotic responses of breast cancer cell lines to PPAR ligands.

  11. Anti-proliferative effect and phytochemical analysis of Cymbopogon citratus extract.

    Science.gov (United States)

    Halabi, Mohammed F; Sheikh, Bassem Y

    2014-01-01

    The antiproliferative and antioxidant potential of Cymbopogon citratus (Lemon grass) extracts were investigated. The extracts were isolated by solvent maceration method and thereafter subjected to antiproliferative activity test on five different cancer cells: human colon carcinoma (HCT-116), breast carcinoma (MCF-7 and MDA-MB 231), ovarian carcinoma (SKOV-3 and COAV), and a normal liver cell line (WRL 68). The cell viability was determined using MTT assay. The DPPH radical scavenging assay revealed a concentration dependent trend. A maximum percentage inhibition of 45% and an IC50 of 278  μg/mL were observed when aqueous extract was evaluated. In contrast, 48.3% and IC50 of 258.9  μg/mL were observed when 50% ethanolic extract was evaluated. Both extracts at concentration of 50 to 800  μg/mL showed appreciative metal chelating activity with IC50 value of 172.2 ± 31  μg/mL to 456.5 ± 30  μg/mL. Depending on extraction solvent content, extract obtained from 50% ethanolic solvent proved to be more potent on breast cancer MCF-7 cell line (IC50 = 68  μg/mL). On the other hand, 90% ethanolic extract showed a moderate potency on the ovarian cancer (COAV) and MCF-7 cells having an IC50 of 104.6  μg/mL each. These results suggested antiproliferative efficacy of C. citratus ethanolic extract against human cancer cell lines.

  12. Persons with moderate Alzheimer's disease use simple technology aids to manage daily activities and leisure occupation.

    Science.gov (United States)

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Renna, Caterina; Pinto, Katia; De Vanna, Floriana; Caffò, Alessandro O; Stasolla, Fabrizio

    2014-09-01

    Two studies assessed technology-aided programs to support performance of daily activities and selection/activation of music items with patients with moderate Alzheimer's disease. In Study I, four patients were presented with activity-related pictorial instructions via a computer fitted with inexpensive, commercial software. In Study II, four patients were (a) presented with different music options and (b) allowed to select and activate the preferred option via a microswitch response. Study I showed that each patient learned to perform the two activities available with percentages of correct responses exceeding 85 by the end of the intervention. Study II showed that all patients learned to choose and activate music options. Psychology students, employed in a social validation check, scored the patients' behavior within the program better than their behavior in a control situation. The relevance and usability of simplified pictorial-instruction programs and music choice programs for patients with moderate Alzheimer's disease were discussed.

  13. Perceptions of the Neighborhood Environment and Children's Afterschool Moderate-to-Vigorous Physical Activity.

    Science.gov (United States)

    McDonald, Samantha; Dowda, Marsha; Colabianchi, Natalie; Porter, Dwayne; Dishman, Rod K; Pate, Russell R

    2015-05-01

    Previous research suggests the neighborhood environment may be an important influence on children's physical activity (PA) behaviors; however, findings are inconsistent. The purpose of this study was to further understand the relationship between perceptions of the neighborhood environment and children's afterschool moderate-to-vigorous PA. Utilizing a structural equation modeling technique, we tested a conceptual model linking parent and child perceptions of the neighborhood environment, parent support for PA, and child outdoor PA with children's afterschool moderate-to vigorous PA. We found that child perception of the neighborhood environment and outdoor PA were positively associated with afterschool moderate-to-vigorous PA. In addition, parent support for PA positively influenced children's outdoor PA. The neighborhood environment and outdoor activity appear to play an influential role on children's afterschool PA behaviors.

  14. Synthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines.

    Science.gov (United States)

    Cankara Pirol, Şeyma; Çalışkan, Burcu; Durmaz, Irem; Atalay, Rengül; Banoglu, Erden

    2014-11-24

    We synthesized a series of novel amide derivatives of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid and assessed their antiproliferative activities against three human cancer cell lines (Huh7, human liver; MCF7, breast and HCT116, colon carcinoma cell lines) with the sulforhodamine B assay. Compound 4j with 2-chloro-4-pyridinyl group in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 1.6 μM, 3.3 μM and 1.1 μM for Huh7, MCF7 and HCT116 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G1 phase as an indicator of apoptotic cell death induction. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess potential in the design of more potent compounds for intervention with cancer cell proliferation.

  15. Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

    NARCIS (Netherlands)

    Beulens, J.W.J.; Berg, R. van den; Kok, F.J.; Helander, A.; Vermunt, S.H.F.; Hendriks, H.F.J.

    2008-01-01

    Background and aims: To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results: Eleven lean (BMI: 18.5-25 kg/m2) and 9 overweight (BMI

  16. Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

    NARCIS (Netherlands)

    Beulens, J.W.J.; Berg, van den R.; Kok, F.J.; Helander, A.; Vermunt, S.H.F.; Hendriks, H.F.J.

    2008-01-01

    Background and aims To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results Eleven lean (BMI: 18.5¿25 kg/m2) and 9 overweight (BMI &g

  17. Conscientiousness, extroversion, and action control: Comparing moderate and vigorous physical activity

    NARCIS (Netherlands)

    de Bruijn, G.J.; de Groot, R.; van den Putte, B.; Rhodes, R.E.

    2009-01-01

    The present study explored the influence of the Big Five dimensions extroversion and conscientiousness on action control regarding both moderate and vigorous physical activity within the framework of the theory of planned behavior (TPB). Prospective data were available from 186 respondents, who comp

  18. Moderate-intensity physical activity ameliorates the breast cancer risk in diabetic women

    National Research Council Canada - National Science Library

    Torres-Mejía, Gabriela; Angeles-Llerenas, Angélica; Ortega-Olvera, Carolina; Lazcano-Ponce, Eduardo; Ziv, Elad; Pulido-Rodríguez, José; García-Solis, Manuel de Jesús; Murillo-Zamora, Efrén; Vázquez-Lara, Julia; Romieu, Isabelle

    2012-01-01

    .... The association between diabetes and BC risk decreased with increasing tertiles of moderate-intensity physical activity (odds ratio [OR] = 4.9 [95% CI 2.3-10.8]; 3.0 [1.3-6.9]; and 1.0 [0.1-9.2...

  19. Marketing Activities to Support ‘Moderately Novel’ Product Innovation: Insights from the Chemical Industry

    NARCIS (Netherlands)

    Smits, A.A.J.; Vissers, G.A.N.; Dankbaar, B.

    2015-01-01

    Scholars often follow a contingency approach to study which marketing activities are suitable for a particular type of product innovation project, thereby making a distinction between incremental and radical innovation only. ‘Moderately novel’ projects, which have intermediate levels of newness, hav

  20. The antipsoriatic agent monomethylfumarate has antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes.

    Science.gov (United States)

    Helwa, Inas; Patel, Ravi; Karempelis, Peter; Kaddour-Djebbar, Ismail; Choudhary, Vivek; Bollag, Wendy B

    2015-01-01

    Monomethylfumarate (MMF) is thought to be the bioactive ingredient of the drug Fumaderm (Biogen Idec, Cambridge, MA), licensed in Germany since 1994 for the treatment of moderate-to-severe psoriasis. Psoriasis is a common inflammatory hyperproliferative skin disorder that involves cross-talk between different cell types, including immune cells and keratinocytes. Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation, and inflammation, with the psoriatic cytokine network maintained by communication between immune cells and keratinocytes. Recently, there is increasing evidence regarding the pivotal role of keratinocytes in mediating the disease process, and these cells can be regarded as safe therapeutic targets. From the data available on human subjects treated with Fumaderm, MMF is an effective antipsoriatic agent with known effects on immune cells. However, little is known about its direct effects on keratinocytes. We hypothesized that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes. Indeed, MMF dose-dependently inhibited [(3)H]thymidine incorporation into DNA, indicating a direct antiproliferative action on keratinocytes. MMF significantly increased the protein level of keratin 10, the early keratinocyte differentiation marker, and the activity of transglutaminase, a late differentiation marker. These results are consistent with an ability of MMF to promote keratinocyte differentiation and inhibit proliferation, thereby improving psoriatic lesions. In 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced keratinocytes, MMF significantly inhibited the expression of the proinflammatory cytokines, tumor necrosis factor-α (TNFα), interleukin-6, and interleukin-1α as well as the production of TNFα. Our results support the notion that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes, highlighting its potential use as a multifactorial

  1. Five new 3,4-seco-lanostane-type triterpenoids with antiproliferative activity in human leukemia cells isolated from the roots of Kadsura coccinea.

    Science.gov (United States)

    Wang, Nan; Li, Zhan-lin; Song, Dan-dan; Li, Wei; Pei, Yue-hu; Jing, Yong-kui; Hua, Hui-ming

    2012-10-01

    Five new 3,4-seco-lanostane-type triterpenoids, seco-coccinic acids G-K (1-5), and a known compound, seco-coccinic F, were isolated from the roots of Kadsura coccinea (Lem.) A. C. Sm. Their structures were elucidated by spectroscopic methods, including 2D-NMR and HR-MS techniques. The cell growth inhibitory effects of these compounds were assayed in human leukemia HL-60 cells, and it was found that 1, 5, and 6 showed antiproliferative effects with GI₅₀ values of 28.4, 15.2, and 16.6 µM, respectively. Georg Thieme Verlag KG Stuttgart · New York.

  2. Ultrasonic promoted synthesis of novel s-triazine-Schiff base derivatives; molecular structure, spectroscopic studies and their preliminary anti-proliferative activities

    Science.gov (United States)

    El-Faham, Ayman; Soliman, Saied M.; Ghabbour, Hazem A.; Elnakady, Yasser A.; Mohaya, Talal A.; Siddiqui, Mohammed R. H.; Albericio, Fernando

    2016-12-01

    Novel series of s-triazine-Schiff base derivatives were synthesized employing ultrasonic irradiation and characterized by NMR (1H and 13C), FT-IR, and elemental analysis. The use of ultrasonic irradiation has allowed the preparation of the target products with better yields in shorter reaction time and excellent purities compared to the conventional heating. X-ray single crystal diffraction experiments verified the molecular structure of four from the new prepared s-triaizne-Schiff base derivatives. The molecular structures of the studied compounds are computerized using DFT/B3LYP method. The effects of substituent at the triazine and phenyl ring on the electronic and spectroscopic properties of the studied compounds were also investigated. The natural atomic charges showed that pipridino-s-triazine derivatives are richer in electrons than those having morpholino derivatives. The anti-proliferative effects for the prepared compounds were tested against three different cancer cell lines.

  3. COMPARISON OF CLINICAL ACTIVITY OF PIMECROLIMUS IN PEDIATRIC PATIENTS WITH MILD AND MODERATE ATOPIC DERMATITIS

    Directory of Open Access Journals (Sweden)

    E.V. Deeva

    2008-01-01

    Full Text Available Atopic dermatitis (ad is prevalent disease in younger children. Calcium inhibitor pimecrolimus (elidel, cream 1% is the latest anti-inflammatory drug offered for management of ad. The activity of pimecrolimus was evaluated in open, prospective, randomized, comparison trial, on 60 children (age from 3 months to 7 years with mild and moderate ad. Pimecrolimus was more effective in management of mild ad on the assumption of regular use of drug (TIS < 17, and topical corticosteroids were effective in patients with moderate ad.Key words: children, atopic dermatitis, pimecrolimus, topical corticosteroids, management.

  4. A new friedelane triterpenoid and saponin with moderate antimicrobial activity from the stems of Drypetes laciniata

    Institute of Scientific and Technical Information of China (English)

    Simone Veronique Fannang; Victor Kuete; Celine Mbazoa Djama; Marlise Diane J. Dongfack; Jean Duplex Wansi; Francois Tillequin; Elisabeth Seguin; Elizabeth Chosson; Jean Wandji

    2011-01-01

    A new friedelane-type triterpene named 3β-hydroxyfriedelane-7,12,22-trione, as well as nine known compounds were isolated from the whole stems of Drypetes laciniata Hutch. (Euphorbiaceae). Their structures were established on the basis of spectroscopic methods. The new triterpene derivative and a known saponin were tested for antimicrobial and antifungal activities and they appeared to be moderate active.

  5. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.

    Science.gov (United States)

    Eldehna, Wagdy M; Almahli, Hadia; Al-Ansary, Ghada H; Ghabbour, Hazem A; Aly, Mohamed H; Ismael, Omnia E; Al-Dhfyan, Abdullah; Abdel-Aziz, Hatem A

    2017-12-01

    Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC50 = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC50 = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

  6. Physical activity moderates the association between nicotine dependence and depression among U.S. smokers.

    Science.gov (United States)

    Loprinzi, Paul D; Walker, Jerome F; Kane, Christy; Cardinal, Bradley J

    2014-01-01

    Research demonstrates that nicotine dependence and depression are associated and that physical activity is effective in reducing depression symptoms. However, our understanding of the potential beneficial effects of physical activity on depression in current smokers is more limited. The purpose of this study was to examine whether physical activity moderates the association between nicotine dependence and depression in U.S. smokers. Cross-sectional. National Health and Nutrition Examination Survey 2005-2006. Four hundred forty-one current adult smokers. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess nicotine dependence and depression. Effect modification and statistical interaction models were used. Both models were significant. With regard to the statistical interaction model, and after controlling for age, gender, race/ethnicity, education, comorbidity index, homocysteine, cotinine, total cholesterol, sedentary behavior, and vitamins C, D, and E, objectively measured physical activity moderated the association between nicotine dependence and depression (interaction variable: odds ratio = 3.43; 95% confidence interval: 1.02-11.51; p = .04). In this national sample of current smokers, physical activity moderated the association between nicotine dependence and depression. These results suggest that those individuals with nicotine dependence and who are less physically active are more likely to be depressed than what would be expected on the basis of the individual effects of nicotine and physical inactivity separately.

  7. 葡萄籽多酚化合物抗氧化能力与抗癌细胞增殖活性的评价%Antioxidant properties and antiproliferative activities of grape seed phenolic compounds on cancer cell culture

    Institute of Scientific and Technical Information of China (English)

    夏兰兰; 张雅丽; 朱磊; 邓嘉进; 曲桂芹; 卢江

    2011-01-01

    Purpose: To study the antioxidant properties and antiproliferative activities of grape seed phenlic compounds on Petri-Dish cultured cancer cells. Methods: Three phenolic compound parameters(total phenols, flavonoids, and flavan-3-ols) and three antioxidant property parameters DPPH(2,2-diphenyi- 1-picrylhydrazyl) radical scavenging, ABTS 2, 2-azino-di-(3-ethylben -zothialozine-sulphonic acid) radical scavenging and FRAP(ferric reducing antioxidant power), were measured. In-vitro cultured human liver cancer cells-HepG2 were treated with extracts of grape seed phenlic compounds in different concentration for 24 h, and were measured for proliferation ability by MTT assay. Results: Phenolic compounds,antioxidant properties and antiproliferative activities were different among variant grape seed extracts. Large quantity of phenolic compounds were remained in grape pomace. V. vinifera "Cabernet Sauvignon"had higher values of phenolic compounds, antioxidant properties and antiproliferative activities than V.rotundifolia "Noble". Conclusions: Grape seed phenolic extracts from both fresh fruit and pomace showed antioxidant properties and antiproliferative activities.%目的:探讨葡萄鲜果及酿酒皮渣中葡萄籽提取物中的酚类化合物含量,抗氧化特性及对癌细胞增殖的抑制作用。方法:乙醇法提取葡萄籽中多酚化合物,分光光度计法测定三大酚类化合物参数(总酚、类黄酮类、黄烷-3-醇类)及3种抗氧化性能参数(DPPH)及ABTS自由基清除能力,FRAP分析)。体外培养肝癌细胞HepG2,建立细胞模型,不同浓度的提取物作用于癌细胞后,采用四甲基偶氮唑盐比色法(MTT法)检测多酚提取物对癌细胞增殖的抑制作用。结果:不同样品葡萄籽所含酚类化合物、抗氧化性能、抗癌细胞增殖能力均不同,酿酒皮渣的葡萄籽中仍含有大量的多酚化合物,其中欧亚种赤霞珠鲜果

  8. Antiproliferative, Antimicrobial and Apoptosis Inducing Effects of Compounds Isolated from Inula viscosa

    OpenAIRE

    2012-01-01

    The antiproliferative and antimicrobial effects of thirteen compounds isolated from Inula viscosa (L.) were tested in this study. The antiproliferative activity was tested against three cell lines using the MTT assay. The microdilution method was used to study the antimicrobial activity against two Gram positive bacteria, two Gram negative bacteria and one fungus. The apoptotic activity was determined using a TUNEL colorimetric assay. Scanning electron microscopy was used to study the morphol...

  9. Practice of walking, moderate and vigorous physical activity and associated factors in first year undergraduate students

    Directory of Open Access Journals (Sweden)

    Gaia Salvador Claumann

    2014-12-01

    Full Text Available The changes that occur with the beginning of university life may interfere with the practice of physical activities by students. The aim was to investigate the association between the practice of walking, moderate and vigorous physical activities with sociodemographic factors and weight status in freshman students in the first semester of the first year of a public university in Florianopolis/SC. This study assessed198 students (86 men and 112 women. The practice of physical activities was collected with the International Physical Activity Questionnaire – IPAQ, short version. Students of human and educational sciences reported higher amounts of moderate physical activity when compared to health and exact science counterparts (p< 0.05. It was verified that male students, from higher economic status, from the health sciences, and full-time students showed higher time of practice of vigorous physical activity (p< 0.05. Significant associations were also observed between study period and walking, and between gender, scientific field and vigorous physical activity. It was concluded that the variables associated with the practice of physical activity differ according to the type and intensity of physical activity.

  10. Isolation and characterization of 2-hydroxy-9,10-anthraquinone from Streptomyces olivochromogenes (ERINLG-261 with antimicrobial and antiproliferative properties

    Directory of Open Access Journals (Sweden)

    Chandrasekar Balachandran

    2016-06-01

    Full Text Available Abstract Currently Streptomyces is one of the most important antibiotic producing microorganisms against several diseases. In the present study Streptomyces olivochromogenes ERINLG-261 was isolated from the soil samples of the Mudumalai hills, Western Ghats, India. Morphological, physiological, biochemical and 16S rRNA studies strongly suggested that this isolate belonged to the genus Streptomyces. ERINLG-261 showed good antimicrobial activity against different bacteria and fungi in Micromonospora fermentation medium. The active ethyl acetate extract was packed in column chromatography over silica gel which led to the isolation of 2-hydroxy-9,10-anthraquinone as the active principle. The isolated compound showed good antimicrobial activity against tested bacteria and fungi in minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC studies. The compound showed moderate in vitro antiproliferative activity against A549 and COLO320 cells. The compound was subjected to molecular docking studies for the inhibition of Topoisomerase, TtgR and Beta-lactamase enzymes which are targets for antimicrobials. Docking results of the compound showed low docking energy with these enzymes indicating its usefulness as antimicrobial agent. This is the first report of antimicrobial and antiproliferative activity of 2-hydroxy-9,10-anthraquinone isolated from Streptomyces olivochromogenes along with molecular docking studies.

  11. A novel ribonuclease with antiproliferative activity toward leukemia and lymphoma cells and HIV-1 reverse transcriptase inhibitory activity from the mushroom, Hohenbuehelia serotina.

    Science.gov (United States)

    Zhang, Rui; Zhao, Liyan; Wang, Hexiang; Ng, Tzi Bun

    2014-01-01

    In this study, a 27-kDa ribonuclease (RNase) was purified from the dried fruiting bodies of the mushroom, Hohenbuehelia serotina. The isolation protocol involved anion exchange chromatography, affinity chromatography, cation exchange chromatography and gel filtration in succession. The RNase was unadsorbed on DEAE-cellulose, but was adsorbed on Affi-gel blue gel and CM-cellulose. The N-terminal amino acid sequence was TVGGSLAEKGN which showed homology to other fungal RNases to a certain degree. The RNase exhibited maximal RNase activity at pH 5 and 80˚C. It demonstrated the highest ribonucleolytic activity toward poly(C), a relatively high activity toward poly(U), and a considerably weaker activity toward poly(A) and (G). The RNase inhibited human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with an IC50 of 50 µM and reduced [3H-methyl]-thymidine uptake by L1210 leukemia cells and MBL2 lymphoma cells with an IC50 of 25 µM and 40 µM, respectively.

  12. Antiproliferative Diterpenes from a Malleastrum sp. from the Madagascar dry forest.

    Science.gov (United States)

    Liu, Yixi; Wiedle, C Houston; Brodie, Peggy J; Callmander, Martin W; Rakotondrajaona, R; Rakotobe, Etienne; Rasamison, Vincent E; Kingston, David G I

    2015-09-01

    An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (-)-kolavenol (4), and the known labdane diterpene 3-oxo-ent-Iabda-8(17),13-dien-15,16-olide (5). Compounds 1, 3, and 4 showed moderate antiproliferative activities against the A2780 ovarian cancer cell line, with the IC50 values of 3.01 ± 0.8, 7.84 ± 0.2, and 17.9 ± 3 µM, respectively. The structure elucidations of all compounds were carried out based on analysis of NMR and mass spectroscopic data. The relative stereochemistry of compound 1 was determined by NOESY NMR spectrum.

  13. Ion density and temperature variations at altitude of 500 km during moderate seismic activity

    Science.gov (United States)

    Bardhan, Ananna; Khurana, M. S.; Bahal, B. M.; Aggarwal, Malini; Sharma, D. K.

    2017-02-01

    Ionospheric ions (O+ and H+) and temperature (Ti) as precursory parameters to seismic activity have been analysed from year 1995 till 1998, using SROSS-C2 (average altitude range of ∼500 km) satellite measurements for moderate magnitude earthquakes. The details of seismic events during this period are downloaded from United State Geological Survey (USGS) and National Earthquake Information Centre (NEIC) website. 13 seismic events of moderate magnitude (M = 4-5.5) from 1995 to 1998, using SROSS-C2 satellite measurements have been analysed. During seismic affected period, considerable decrease in the density of heavier ion - O+ and increase in the ion temperature (Ti) is observed during all the selected events. Lighter ion - H+ doesn't show any significant change. Electric field and electromagnetic emissions generated due to seismogenic activity could be the plausible initializing agents responsible for change in ion concentration and temperature values during these events.

  14. Association of sedentary time with mortality independent of moderate to vigorous physical activity

    DEFF Research Database (Denmark)

    Koster, Annemarie; Caserotti, Paolo; Patel, Kushang V

    2012-01-01

    Sedentary behavior has emerged as a novel health risk factor independent of moderate to vigorous physical activity (MVPA). Previous studies have shown self-reported sedentary time to be associated with mortality; however, no studies have investigated the effect of objectively measured sedentary...... time on mortality independent of MVPA. The objective our study was to examine the association between objectively measured sedentary time and all-cause mortality....

  15. Socio-Demographic Moderators of Environment-Physical Activity Associations: Results From the International Prevalence Study.

    Science.gov (United States)

    Perez, Lilian G; Conway, Terry L; Bauman, Adrian; Kerr, Jacqueline; Elder, John P; Arredondo, Elva M; Sallis, Jim F

    2017-08-03

    Associations between the built environment and physical activity (PA) may vary by socio-demographic factors. However, such evidence from international studies is limited. This study tested moderating effects of socio-demographic factors on associations between perceived environment and self-report total PA among adults from the International Prevalence Study. Between 2002-2003, adults from nine countries (N=10,258) completed surveys assessing total PA (IPAQ-short), perceived environment, and socio-demographics (age, gender, and education). Total PA was dichotomized as meeting/not meeting a) high PA levels and b) minimum PA guidelines (PAG). Logistic models tested environment by socio-demographic interactions (24 total). Education and gender moderated the association between safety from crime and meeting high PA levels (interaction p<0.05), with inverse associations found only among the high-education group and men. Education and gender also moderated associations of safety from crime and the presence of transit stops with meeting minimum PAG (interaction p<0.05), with positive associations found for safety from crime only among women and presence of transit stops only among men and the high-education group. The limited number of moderating effects found provides support for population-wide environment-PA associations. International efforts to improve built environments are needed to promote health-enhancing PA, and maintain environmental sustainability.

  16. The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Mariana P.C. [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal); Nunes-Correia, Isabel [Center for Neuroscience and Cell Biology, Flow Cytometry Unit, University of Coimbra, 3000-354 Coimbra (Portugal); Santos, Armanda E., E-mail: aesantos@ci.uc.pt [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal); Custódio, José B.A. [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal)

    2014-02-15

    Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: • MK-801 and memantine decrease melanoma cell proliferation. • The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. • These combinations greatly enhance the effects of the compounds individually. • MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. • The combination of MK-801 and antiestrogens is an innovative strategy for melanoma.

  17. Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones have enhanced activity under high glucose conditions

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    de Dios Stephanie T

    2007-10-01

    Full Text Available Abstract Background Inhibition of vascular smooth muscle cell (vSMC proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods VSMC proliferation was investigated by [3H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]-thymidine uptake. Cell cycle events were analyzed by FACS. Results VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose and high (25 mM glucose increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P 3H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [3H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations. The sulfonylureas chlorpropamide and gliclazide had no inhibitory effect on vSMC proliferation assessed by either [3H

  18. In vitro antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone induced apoptosis against COLO320 cells through cytochrome c release caspase mediated pathway with PI3K/AKT and COX-2 inhibition.

    Science.gov (United States)

    Balachandran, C; Emi, N; Arun, Y; Yamamoto, N; Duraipandiyan, V; Inaguma, Yoko; Okamoto, Akinao; Ignacimuthu, S; Al-Dhabi, N A; Perumal, P T

    2016-04-05

    The present study investigated the anticancer activity of 2,3-dihydroxy-9,10-anthraquinone against different cancer cells such as MCF-7, COLO320, HepG-2, Skov-3, MOLM-14, NB-4, CEM, K562, Jurkat, HL-60, U937, IM-9 and Vero. 2,3-dihydroxy-9,10-anthraquinone showed good antiproliferative activity against COLO320 cells when compared to other tested cells. The cytotoxicity results showed 79.8% activity at the dose of 2.07 μM with IC50 value of 0.13 μM at 24 h in COLO320 cells. So we chose COLO320 cells for further anticancer studies. mRNA expression was confirmed by qPCR analysis using SYBR green method. Treatment with 2,3-dihydroxy-9,10-anthraquinone was found to trigger intrinsic apoptotic pathway as indicated by down regulation of Bcl-2, Bcl-xl; up regulation of Bim, Bax, Bad; release of cytochrome c and pro-caspases cleaving to caspases. Furthermore, 2,3-dihydroxy-9,10-anthraquinone stopped at G0/G1 phase with modulation in protein levels of cyclins. On the other hand PI3K/AKT signaling plays an important role in cell metabolism. We found that 2,3-dihydroxy-9,10-anthraquinone inhibits PI3K/AKT activity after treatment. Also, COX-2 enzyme plays a major role in colorectal cancer. Our results showed that the treatment significantly reduced COX-2 enzyme in COLO320 cells. These results indicated antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone involving apoptotic pathways, mitochondrial functions, cell cycle checkpoint and controlling the over expression genes during the colorectal cancer. Molecular docking studies showed that the compound bound stably to the active sites of Bcl-2, COX-2, PI3K and AKT. This is the first report of anticancer mechanism involving 2,3-dihydroxy-9,10-anthraquinone in COLO320 cells. The present results might provide helpful suggestions for the design of antitumor drugs toward colorectal cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II).

    Science.gov (United States)

    Kovala-Demertzi, Dimitra; Hadjipavlou-Litina, Dimitra; Staninska, Malgorzata; Primikiri, Alexandra; Kotoglou, Chronis; Demertzis, Mavroudis A

    2009-06-01

    Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7

  20. Does physical activity moderate the relationship between depression symptomatology and low back pain?

    DEFF Research Database (Denmark)

    Hübscher, Markus; Hartvigsen, Jan; Fernandez, Matthew

    2016-01-01

    PURPOSE: To investigate whether depression symptomatology is associated with low back pain (LBP) in twins aged 70+ and whether this effect depends on a person's physical activity (PA) status. METHODS: This prospective cohort and nested case-control study used a nationally representative sample....... This effect is supposedly not attributable to genetic or shared environmental factors. Physical activity did not moderate the effect of depression symptomatology on LBP....... of twins. Data on depression symptomatology (modified Cambridge Mental Disorders Examination) and self-reported PA were obtained from the Longitudinal Study of Aging Danish Twins using twins without LBP at baseline. Associations between depression symptomatology (highest quartile) at baseline and LBP two...

  1. Factors associated with walking, moderate and vigorous physical activities in adolescents

    Directory of Open Access Journals (Sweden)

    V.C. Barbosa Filho

    2011-01-01

    Full Text Available This study aimed at investigating the relationship between a set of variables (adolescents' gender, age, economic level, nutritional status, and fathers' educational level and physical activity practices. The sample consisted of 578 students from a public school, aged between 11 and 16 years. The International Physical Activity Questionnaire (IPAQ, version 8, short form was applied in order to measure their physical activity practices. Chi-square, independent t test and one-way ANOVA were implemented. Thirteen percent of adolescents were physically inactive and no significant difference was found between gender (p > .05. Compared to boys, girls spent more time in walking (p = .019 and vigorous activities (p = .017. Adolescents aged 14-16 years spent more time in walking compared with those aged 11-12 years (p = .026 and 13-year-olds (p = .006. There was a positive association between economic level and time spent in moderate physical activity (p = .034.

  2. Activity Of The Moderate And Radical Islamic Organizations In The European States

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    Nina V. Volodina

    2014-12-01

    Full Text Available In the present article author examines various aspects of Islamic organizations functioning in modern European countries. In the world the dangerous situation due to the spread of radical Islamic views, this is directly related to safety arose. Author researches some aspects of Islamic organizations in Europe functioning and their division into "moderate" and "radical". Author notes that the concept of "moderate Islam" is actively used in the western countries. In the article it is emphasized that supporters of such division believe that it is the "moderate Islamists" may help deal with the terrorist threat. Author gives definition of "religious extremism" and analyzes activities of Islamic organizations in Germany and France, as well as other European countries at the present stage of their development. In the process of study author pays enough attention to the notion of "spreading radicalism within the law", analyze existing legal acts. In the article problems of financing extremist organizations is pointed out and the need to create a set of joint measures to counter extremism and terrorism by Russian Federation and European countries, further improvement of law-enforcement is identified.

  3. Benefits of achieving vigorous as well as moderate physical activity recommendations: evidence from heart rate complexity and cardiac vagal modulation.

    Science.gov (United States)

    Soares-Miranda, Luisa; Sandercock, Gavin; Vale, Susana; Silva, Pedro; Moreira, Carla; Santos, Rute; Mota, Jorge

    2011-07-01

    The aim of this study was to examine differences in traditional heart rate variability measurements and heart rate complexity (sample entropy) in young adults grouped by objectively measured achievement of either moderate or both moderate and vigorous physical activity recommendations. Of 168 young adults tested (86 females, 82 males; age 20.5 ± 1.2 years), 119 achieved only recommendations for moderate physical activity (moderate group) and 49 achieved recommendations for both moderate and vigorous physical activity (vigorous group). Analysis of covariance controlling for sex, weekly minutes of moderate physical activity, and percentage of body fat was used to assess between-group differences in heart rate variability and heart rate complexity. Logistic regression analysis was used to determine the group characteristics that best predicted high heart rate complexity and vagal indices of heart rate variability. The majority of the autonomic measures were higher (P heart rate complexity and higher heart rate variability. Young adults engaged in regular vigorous physical activity were more than twice as likely to have high heart rate complexity than those involved in predominantly moderate exercise. These findings suggest that vigorous physical activity is more closely associated with high heart rate complexity than moderate physical activity in young adults.

  4. Longitudinal Effects of Personality on Physical Activity Among College Students: Examining Executive Function as a Potential Moderator.

    Science.gov (United States)

    Joyner, Chelsea; Loprinzi, Paul D

    2017-01-01

    Objective The purpose of this study was to examine the relationship between personality and physical activity, with a specific focus on whether executive function moderates this relationship. Methods One hundred twenty-six young adults provided complete data at baseline and the five-month follow-up assessment. Executive function was assessed via the parametric Go/No-Go computer task; outcome measures of parametric Go/No-Go were mean reaction time and percent of correct target detection across executive function tasks (simple rule and repeating rule). Personality and moderate-to-vigorous physical activity were assessed via validated questionnaires; one-week test-retest was established on a random sample of the participants, with pedometry employed in the subsample. Results Individuals with a higher baseline conscientiousness personality type had greater five-month follow-up moderate-to-vigorous physical activity (β = 18.5; 95% confidence interval: 5.3, 31.7; p = .006). There was no evidence of an interaction effect for personality trait and executive function on five-month follow-up moderate-to-vigorous physical activity. Conclusion The personality trait conscientiousness was associated with greater moderate-to-vigorous physical activity. However, there was no evidence to suggest that executive function moderates the role between personality and moderate-to-vigorous physical activity. Thus, if confirmed by future work, personality may exert its effects on moderate-to-vigorous physical activity independent of executive function level.

  5. Lipid Composition, Fatty Acids and Sterols in the Seaweeds Ulva armoricana, and Solieria chordalis from Brittany (France): An Analysis from Nutritional, Chemotaxonomic, and Antiproliferative Activity Perspectives.

    Science.gov (United States)

    Kendel, Melha; Wielgosz-Collin, Gaëtane; Bertrand, Samuel; Roussakis, Christos; Bourgougnon, Nathalie; Bedoux, Gilles

    2015-09-02

    Lipids from the proliferative macroalgae Ulva armoricana (Chlorophyta) and Solieria chordalis (Rhodophyta) from Brittany, France, were investigated. The total content of lipids was 2.6% and 3.0% dry weight for U. armoricana and S. chordalis, respectively. The main fractions of S. chordalis were neutral lipids (37%) and glycolipids (38%), whereas U. armoricana contained mostly neutral lipids (55%). Polyunsaturated fatty acids (PUFA) represented 29% and 15% of the total lipids in U. armoricana and S. chordalis, respectively. In both studied algae, the phospholipids were composed of PUFA for 18%. In addition, PUFA were shown to represent 9% and 4.5% of glycolipids in U. armoricana and S. chordalis, respectively. The essential PUFA were 16:4n-3, 18:4n-3, 18:2n-3, 18:2n-6, and 22:6n-3 in U. armoricana, and 20:4n-6 and 20:5n-3 in S. chordalis. It is important to notice that six 2-hydroxy-, three 3-hydroxy-, and two monounsaturated hydroxy fatty acids were also identified and may provide a chemotaxonomic basis for algae. These seaweeds contained interesting compounds such as squalene, α-tocopherol, cholest-4-en-3-one and phytosterols. The antiproliferative effect was evaluated in vitro on human non-small-cell bronchopulmonary carcinoma line (NSCLC-N6) with an IC50 of 23 μg/mL for monogalactosyldiacylglycerols isolated from S. chordalis and 24 μg/mL for digalactosyldiacylglycerols from U. armoricana. These results confirm the potentialities of valorization of these two species in the fields of health, nutrition and chemotaxonomy.

  6. Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells.

    Science.gov (United States)

    Pereira, Andreia; Bester, Megan; Soundy, Puffy; Apostolides, Zeno

    2016-09-01

    Context Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown that root extracts are rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. Objective This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). Materials and methods The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukaemia cell line at concentrations of 0-150 μg/mL. The effect on cell growth was determined with sulphorhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. The effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. Results Dihydroxycoumarin sulphates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL were observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 value of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 value of 9.7 μg/mL). The PST arrested Jurkat cells at the G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. Conclusion We present evidence that P. sidoides has cancer cell type-specific anti-proliferative effects and may be a source of novel anticancer molecules.

  7. The social context moderates the relationship between neighborhood safety and adolescents' activities

    Directory of Open Access Journals (Sweden)

    Sarah-Jeanne Salvy

    2017-06-01

    Full Text Available Studies of neighborhood safety and physical activity have typically neglected to consider the youth's peer context as a modifier of these relationships. This study fills this gap in testing the independent and interactive effects of perceived neighborhood safety and time spent with friends and peers on young adolescents' physical activity and sedentary behavior. Participants (N = 80; ages 13–17 completed the Pedestrian/Traffic Safety and Crime Safety subscales of the adolescent version of the Neighborhood Environment Walkability Scale (NEWS. An experience sampling methodology was used to assess sedentary behaviors/screen time and the social context in which physical activity and sedentary time/behavior occurred. Physical activity was assessed via accelerometry. Multilevel models were used to estimate the relationships between predictors (neighborhood safety and social context and outcomes (physical activity and sedentary time/behavior. Frequency of peer/friend interactions moderated the relationships between neighborhood safety and adolescents' physical activity and sedentary behavior. Specifically, physical activity was more strongly influenced by neighborhood safety among adolescents who reported spending less time with peers and friends than among those who reported frequent peer interactions. Among youths who perceived that their neighborhoods were safer, spending more time with friends and peers was related to greater engagement in sedentary activities, whereas this was not the case among adolescents who perceived that their neighborhoods were less safe. The peer social context moderates the relationship between perceived neighborhood safety and adolescents' physical activity and sedentary behavior. Improving social interactions at the individual level within neighborhoods may decrease concerns of safety.

  8. Atividade antiproliferativa dos extratos e da fração orgânica obtidos das folhas de Virola sebifera Aubl. (Myristicaceae Antiproliferative activity of extracts and fractions from Virola sebifera Aubl. leaves (Myristicaceae

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    Carina Denny

    2007-12-01

    Full Text Available As cascas de Virola sebifera (Myristicaceae são utilizadas por populações indígenas amazônicas em preparações alucinógenas, nas quais foram encontrados alcalóides como a dimetiltriptamina e seus derivados. Considerando a enorme importância dos alcalóides isolados de plantas na terapêutica do câncer e a presença desses compostos em espécies de Virola, o presente trabalho teve por objetivo o estudo da atividade antiproliferativa em cultura de células tumorais humanas de extratos e da fração orgânica, obtidos das folhas de Virola sebifera. O extrato bruto diclorometânico (EBD foi considerado o mais ativo, com seletividade principalmente para a linhagem de pulmão (NCI-460 - IC50: 4,46 µg/mL e para a fração orgânica (FO obtida por extração ácido-base - IC50; 6,91 µg/mL. A atividade observada possivelmente pode ser atribuída a alcalóides ou compostos nitrogenados que foram evidenciados pelo corante Dragendorff. Assim, a purificação da FO será necessária a fim de comprovar a presença de compostos nitrogenados, através de isolamento e determinação estrutural, bem como a participação desses compostos na atividade antiproliferativa observada.Barks of Virola sebifera (Myristicaceae used by Amazonian Indian communities in hallucinogenic snuff preparations have yielded dimethyltryptamine and derivatives. Considering the importance of the alkaloids isolated from plants for the development of chemotherapy, and the presence of these compounds in several Virola species, the scope of this work was to evaluate the antiproliferative activity of the extracts and the organic fraction from Virola sebifera leaves. The crude dichloromethane extract was the most active with selectivity for lung line (NCI-460 - IC50: 4.46 µg/mL, as well as the organic fraction (OF - IC50: 6.91 µg/mL. The observed activity could probably be attributed to alkaloids or nitrogen compounds that were evidenced by the Dragendorff reagent. However, the

  9. Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves’ Orbitopathy

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    Miaoli Lin

    2015-01-01

    Full Text Available Aim. To study the efficacy and safety of subantimicrobial dose (SD doxycycline(50 mg/d in patients with active and moderate-to-severe Graves’ orbitopathy (GO. Methods. Thirteen patients with active and moderate-to-severe GO received once daily oral doxycycline (50 mg/d for 12 wk. Treatment response at 24 wk was used as the primary outcome, measured by a composite of improvement in Clinical Activity Score (CAS, diplopia, motility, soft tissue swelling, proptosis, and eyelid aperture. Secondary outcome was the change of quality of life score (QoL, including visual functioning subscale and appearance subscale. Adverse events were also recorded. Results. Overall improvement was noted in eight out of 13 patients (61.5%, 95% CI 31.6%–86.1%. Both CAS and soft tissue swelling significantly ameliorated in eight patients at 24 wk. Five patients (38.5% had improvement in ocular motility of ≥8 degrees. Eyelid aperture (46.2% also decreased remarkably. For QoL, a significant improvement in appearance subscale (P=0.008 was noted during the study, whereas no difference was observed in visual functioning subscale (P=0.21. Two patients reported mild stomachache at 12 wk. Conclusions. SD doxycycline appears to be effective and safe for the treatment of active and moderate-to-severe GO. It might serve as a new promising therapeutic strategy for GO. This trial is registered with NCT01727973.

  10. Overweight, obesity, steps, and moderate to vigorous physical activity in children.

    Science.gov (United States)

    Oliveira, Luis Carlos; Ferrari, Gerson Luis de Moraes; Araújo, Timóteo Leandro; Matsudo, Victor

    2017-04-27

    The objective of this study is to establish cutoff points for the number of steps/day and minutes/day of moderate to vigorous physical activity in relation to the risk of childhood overweight and obesity and their respective associations. In addition, we aim to identify the amount of steps/day needed to achieve the recommendation of moderate to vigorous physical activity in children from São Caetano do Sul. In total, 494 children have used an accelerometer to monitor steps/day and the intensity of physical activity (min/day). The moderate to vigorous physical activity has been categorized according to the public health recommendation (≤ 60 versus > 60 min/day). Overweight or obesity is defined as body mass index > +1 SD, based on reference data from the World Health Organization. The data on family income, education of parents, screen time, diet pattern, and sedentary time have been collected by questionnaires. Logistic regression and Receiver Operating Characteristic curves have been constructed. On average, boys walked more steps/day (1,850) and performed more min/day of moderate to vigorous physical activity (23.1) than girls. Overall, 51.4% of the children have been classified as eutrophic and 48.6% as overweight or obese. Eutrophic boys walked 1,525 steps/day and performed 18.6 minutes/day more of moderate to vigorous physical activity than those with overweight/obesity (p 0.05). The cutoff points to prevent overweight and obesity in boys and girls were 10,500 and 8,500 steps/day and 66 and 46 min/day of moderate to vigorous physical activity, respectively. The walking of 9,700 steps/day for boys and 9,400 steps/day for girls ensures the scope of the recommendation of moderate to vigorous physical activity. In boys, steps/day and moderate to vigorous physical activity have been negatively associated with body mass index, regardless of race, family income, education of parents, screen time, diet pattern, and sedentary time. We suggest, for steps/day and

  11. Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke

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    Firdaus Fabrice Hannanu

    2017-01-01

    In subacute stroke, fMRI brain activity related to passive movement measured in a sensorimotor network defined by activity during voluntary movement predicted motor recovery better than baseline motor-FMS alone. Furthermore, fMRI sensorimotor network activity measures considered alone allowed excellent clinical recovery prediction and may provide reliable biomarkers for assessing new therapies in clinical trial contexts. Our findings suggest that neural reorganization related to motor recovery from moderate to severe stroke results from balanced changes in ipsilesional MI (BA4a and a set of phylogenetically more archaic sensorimotor regions in the ventral sensorimotor trend, in which OP1 and OP4 processes may complement the ipsilesional dorsal motor cortex in achieving compensatory sensorimotor recovery.

  12. Metabolic syndrome risk score and time expended in moderate to vigorous physical activity in adolescents.

    Science.gov (United States)

    Stabelini Neto, Antonio; de Campos, Wagner; Dos Santos, Géssika Castilho; Mazzardo Junior, Oldemar

    2014-02-14

    The clustering of metabolic syndrome risk factors is inversely related to the amount of physical activity. However, the question remains as to how much daily physical activity is enough to prevent the onset of metabolic disorders in adolescents? Therefore, the objectives of this study were to associate the metabolic risk score with the moderate to vigorous physical activity (MVPA) and to identify the amount of daily physical activity to prevent the onset of the metabolic risk factors in Brazilian adolescents. The study involved 391 participants aged 10 to 18 years. Physical activity was measured by accelerometry. The counts obtained in the different activities were transformed into metabolic equivalents and classified as light (≥ 1.5 but pressure, blood glucose, HDL-C and triglycerides. Time spent in MVPA was inversely associated with the continuous risk score for metabolic syndrome (p adolescents must perform at least 88 minutes per day of MVPA. These findings reinforce previous evidence that physical activity relates to metabolic syndrome in adolescents. This population should be encouraged to gradually replace part of their sedentary time with physical activities.

  13. Wear testing of moderate activities of daily living using in vivo measured knee joint loading.

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    Jörn Reinders

    Full Text Available Resumption of daily living activities is a basic expectation for patients provided with total knee replacements. However, there is a lack of knowledge regarding the impact of different activities on the wear performance. In this study the wear performance under application of different daily activities has been analyzed. In vivo load data for walking, walking downstairs/upstairs, sitting down/standing up, and cycling (50 W & 120 W has been standardized for wear testing. Wear testing of each activity was carried out on a knee wear simulator. Additionally, ISO walking was tested for reasons of comparison. Wear was assessed gravimetrically and wear particles were analyzed. In vivo walking produced the highest overall wear rates, which were determined to be three times higher than ISO walking. Moderate wear rates were determined for walking upstairs and downstairs. Low wear rates were determined for standing up/sitting down and cycling at power levels of 50 W and 120 W. The largest wear particles were observed for cycling. Walking based on in vivo data has been shown to be the most wear-relevant activity. Highly demanding activities (stair climbing produced considerably less wear. Taking into account the expected number of loads, low-impact activities like cycling may have a greater impact on articular wear than highly demanding activities.

  14. Antimicrobial and Antiproliferative Potential of Anadenanthera colubrina (Vell. Brenan

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    Rennaly de Freitas Lima

    2014-01-01

    Full Text Available The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell. Brenan (angico and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC, minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM. Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 (MIC=0.031 mg/mL, with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance (P>0.05. SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell. Brenan as well as a tendency toward diminishing the growth of human tumor cells.

  15. Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium from Corals.

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    Lisa Fujise

    Full Text Available The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium. Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae in aquaria under non-thermal stress (27°C and moderate thermal stress conditions (30°C, and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress con