Obvious Cytotoxic Effect Research Articles

Determining antioxidant activities of lactobacilli by cellular antioxidant assay in mammal cells

Among the beneficial effects of Lactobacillus spp., the common mechanism underlying health protection is believed to be related to antioxidant activity. The antioxidant activities of cell-free suspension (CFS) and strain suspension (SS) of 13 Lactobacillus strains derived from 4 species (L. rhamnosus, L. acidophilus, L. casei, and L. fermenti) were determined. The correlation of CFSs and SSs in different cell lines, as well as the correlation among the three cell models (RAW264.7, Caco-2, and EA.hy926 cell lines), were compared. All CFSs and SSs of lactobacilli showed that they significantly inhibited the production of intracellular reactive oxygen species without creating obvious cytotoxic effects in the three mammal cell lines. These results suggested that RAW264.7, Caco-2, and EA.hy926 cell lines could be used as cell models to assay the cellular antioxidant activity of CFS and SS of lactobacilli. Thus, lactobacilli and by-products are a potential source of natural antioxidants and to reduce oxidative stress.

Mechano growth factor-E regulates apoptosis and inflammatory responses in fibroblast-like synoviocytes of knee osteoarthritis.

This study investigated whether mechano growth factor-E (MGF-E) peptide can regulate apoptosis and inflammation responses in fibroblast-like synoviocytes of osteoarthritis (OA). A (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay was performed to evaluate cytotoxic effects of exogenous MGF-E peptide on OA fibroblast-like synoviocytes (OA-FLS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to check messenger RNA (mRNA) expression levels of lysyl oxidase (LOX) family members (LOX) after OA-FLS treatment using MGF-E peptide. A 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay was performed to identify the influence of MGF-E peptide on proliferation OA-FLS proliferation. Western blot was used to detect biomarkers of endoplasmic reticulum (ER) stress and inflammatory cytokines. Exogenous MGF-E peptide has no obvious cytotoxic effects on OA-FLS and promotes LOX expression in OA-FLS, induce apoptosis and ER stress and down-regulate protein levels of tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Our results suggest that MGF-E peptide possesses potential anti-inflammatory effects, induces cell apoptosis and facilitates repair of OA-FLS. Therefore, MGF-E peptide may have therapeutic potential in patients with OA.

Facile synthesis of fluorescent Au/Ce nanoclusters for high-sensitive bioimaging.

BackgroundTumor-target fluorescence bioimaging is an important means of early diagnosis, metal nanoclusters have been used as an excellent fluorescent probe for marking tumor cells due to their targeted absorption. We have developed a new strategy for facile synthesis of Au/Ce nanoclusters (NCs) by doping trivalent cerium ion into seed crystal growth process of gold. Au/Ce NCs have bright fluorescence which could be used as fluorescent probe for bioimaging.ResultsIn this study, we synthesized fluorescent Au/Ce NCs through two-step hydrothermal reaction. The concentration range of 25–350 μM, Au/Ce NCs have no obvious cell cytotoxicity effect on HeLa, HepG2 and L02 cells. Furthermore, normal cells (L02) have no obvious absorption of Au/Ce NCs. Characterization of synthesized Au/Ce NCs was done by using TEM, EDS and XPS. Then these prepared Au/Ce NCs were applied for in vitro/in vivo tumor-target bioimaging due to its prolonged fluorescence lifetime and bright luminescence properties.ConclusionsThe glutathione stabilized Au/Ce NCs synthesized through hydrothermal reaction possess stable and bright fluorescence that can be readily utilized for high sensitive fluorescence probe. Our results suggest that Au/Ce NCs are useful candidate for in vitro/in vivo tumor bioimaging in potential clinical application.

The use of nanoparticles to deliver nitric oxide to hepatic stellate cells for treating liver fibrosis and portal hypertension.

Polymeric nanoparticles are designed to transport and deliver nitric oxide (NO) into hepatic stellate cells (HSCs) for the potential treatment of both liver fibrosis and portal hypertension. The nanoparticles, incorporating NO donor molecules (S-nitrosoglutathione compound), are designed for liver delivery, minimizing systemic delivery of NO. The nanoparticles are decorated with vitamin A to specifically target HSCs. We demonstrate, using in vitro and in vivo experiments, that the targeted nanoparticles are taken up specifically by rat primary HSCs and the human HSC cell line accumulating in the liver. When nanoparticles, coated with vitamin A, release NO in liver cells, we find inhibition of collagen I and α-smooth muscle actin (α-SMA), fibrogenic genes associated with activated HSCs expression in primary rat liver and human activated HSCs without any obvious cytotoxic effects. Finally, NO-releasing nanoparticles targeted with vitamin A not only attenuate endothelin-1 (ET-1) which elicites HSC contraction but also acutely alleviates haemodynamic disorders in bile duct-ligated-induced portal hypertension evidenced by decreasing portal pressure (≈20%) and unchanging mean arterial pressure. This study clearly shows, for the first time, the potential for HSC targeted nanoparticle delivery of NO as a treatment for liver diseases with proven efficacy for alleviating both liver fibrosis and portal hypertension.

Inhibition of invasion and metastasis by DMBT, a novel trehalose derivative, through Akt/GSK-3β/β-catenin pathway in B16BL6 cells

Invasion, either directly or via metastasis formation, is the main cause of death in cancer patients. Development of efficient anti-invasive agents is an important research challenge. 6,6′-bis (2,3-dimethoxybenzoyl)-a, a-d-trehalose (DMBT), one of brartemicin analogs, was found to be the most potent anti-invasive agent, but the underlying mechanisms are poorly understood. Our current study was to explore the effects of DMBT on invasion and metastasis in B16BL6 cells. Antiproliferation assay and trypan blue exclusion assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found in B16BL6 cells. Wound healing demonstrated that DMBT could inhibit cell migration compared with the normal group. Transwell experiments showed that DMBT could significantly inhibit invasion to the reconstituted basement membrane (P<0.01). We examined the effects of lung metastasis produced by highly metastatic B16BL6 melanoma cells by using experimental metastasis models and BLI analysis. DMBT could significantly suppress lung metastasis in mice. Results from immunohistochemical staining, Western blotting and real-time PCR indicated that the chemopreventive effect of DMBT was attributed to the inhibition of the VEGF and MMP-9 through Akt/GSK-3β/β-catenin and Akt/mTOR signaling pathways. These results suggested that DMBT could be a promising lead molecule for the anti-metastasis and serve as a therapeutic agent to inhibit cancer cell invasion and metastasis.

Dynamic monitoring of the cytotoxic effects of protoberberine alkaloids from Rhizoma Coptidis on HepG2 cells using the xCELLigence system

AimTo investigate the cytotoxic effects of the six protoberberine alkaloids (PAs) from Rhizoma Coptidis on HepG2 cells. MethodA systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations (IC50) were acquired to evaluate the anticancer activity of the PAs. ResultsAll of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μ·mL−1, respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. ConclusionThe xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells. These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.

Synthesis of Hydroxylactams and Esters Derived from Thalidomide and Their Antitumor Activities

A novel and convenient route for the synthesis of a series of thalidomide derivatives is described. Compound 2 was cyclized with different amines under alkaline condition to obtain 4-nitro substituted phthalimidines 3a-d. Hydroxylactams 4a-d were produced via bromination and hydroxylation. Different acyl chlorides were reacted with hydroxylactams to provide the desired esters 5a-d. All compounds were evaluated by MTT assay for their inhibitory activities against HCT-116, MG-63, MCF-7, HUVEC and HMVEC cell lines in vitro. Most of them showed no obvious cytotoxic effect on normal human cells, compounds 4a-d, 5a2, 5a4, 5a5, 5b2, 5c2 and 5d2 exhibited potent antitumor activities, among which compounds 5a2 and 5b2 were more effective than 5-FU.

Cytotoxic Effect on Osteosarcoma MG-63 Cells by Degradation of Magnesium

Biocompatible and biodegradable magnesium (Mg) based metals have attracted great interest for use in orthopedic implants and devices. Based on our previous study that Mg with and without micro-arc oxidation (MAO) coating showed obvious cytotoxic effect on tumor cells due to the increase of pH value during the degradation of Mg, this study further evaluated the cytotoxic effect of Mg and MAO coated Mg on osteosarcoma (MG-63) cells by analyzing the cell adhesion, morphology and number through observation of scanning electron microscope, as well as live/dead staining, lactate dehydrogenase (LDH) activity and 4, 6-diamidino-2-phenylindole (DAPI) assay. The results indicated that, compared to titanium, Mg could strongly inhibit the cell adherence, morphology and number of MG-63 on the surface of the naked Mg, whereas the MAO coated Mg showed relative weak cytotoxic effect on MG-63 cells, expecting that magnesium based metals with suitable coating can be designed to be applied as tumor prosthesis in the clinical practice.

Up-Conversion Nanoparticle Assembled Mesoporous Silica Composites: Synthesis, Plasmon-Enhanced Luminescence, and Near-Infrared Light Triggered Drug Release

A facile process for the preparation of multifunctional nanospheres combining several advantages of mesoporous channels, up-conversion (UC) luminescence, and photothermal responses into one single entity is reported. First, Gd2O3:Yb/Er assembled mesoporous silica with 2D hexagonal (MCM-41) and 3D cubic (MCM-48) network have been prepared via a one-step procedure. Then, gold nanocrystals with diameter of 5 nm are integrated with the amino group functionalized nanocomposites. Upon 980 nm near infrared (NIR) laser irradiation, a wavelength-dependent enhancement of the UC intensities is observed due to the surface plasmon resonance (SPR) effect of attached gold nanoparticles. These composites have good biocompatibility and sustained anticancer drug (doxorubicin, DOX) release properties, making it a promising candidate for drug delivery. Particularly, under 980 nm NIR laser irradiation, the green UC emission overlaps the SPR band of gold nanocrystals, which causes a photothermal effect of gold nanocrystals and induces a rapid DOX release from the Au hybrid materials. This DOX loaded multifunctional system has an obvious cytotoxic effect and photothermally killing enhanced effect on SKOV3 ovarian cancer cells. The endocytosis process was also demonstrated through confocal laser scanning microscope (CLSM) images. Such novel multifunctional anticancer drug delivery systems, which combine hyperthermia with the chemotherapeutic drugs by synergistic effect, should be of high potential in cancer therapy.

Dimethyloxaloylglycine Increases the Bone Healing Capacity of Adipose-Derived Stem Cells by Promoting Osteogenic Differentiation and Angiogenic Potential

Hypoxia inducible factor-1α (HIF-1α) plays an important role in angiogenesis-osteogenesis coupling during bone regeneration, which can enhance the bone healing capacity of mesenchymal stem cells (MSCs) by improving their osteogenic and angiogenic activities. Previous studies transduced the HIF-1α gene into MSCs with lentivirus vectors to improve their bone healing capacity. However, the risks due to lentivirus vectors, such as tumorigenesis, should be considered before clinical application. Dimethyloxaloylglycine (DMOG) is a cell-permeable prolyl-4-hydroxylase inhibitor, which can activate the expression of HIF-1α in cells at normal oxygen tension. Therefore, DMOG is expected to be an alternative strategy for enhancing HIF-1α expression in cells. In this study, we explored the osteogenic and angiogenic activities of adipose-derived stem cells (ASCs) treated with different concentrations of DMOG in vitro, and the bone healing capacity of DMOG-treated ASCs combined with hydrogels for treating critical-sized calvarial defects in rats. The results showed that DMOG had no obvious cytotoxic effects on ASCs and could inhibit the death of ASCs induced by serum deprivation. DMOG markedly increased vascular endothelial growth factor production in ASCs in a dose-dependent manner and improved the osteogenic differentiation potential of ASCs by activating the expression of HIF-1α. Rats with critical-sized calvarial defects treated with hydrogels containing DMOG-treated ASCs had more bone regeneration and new vessel formation than the other groups. Therefore, we believe that DMOG enhanced the angiogenic and osteogenic activity of ASCs by activating the expression of HIF-1α, thereby improving the bone healing capacity of ASCs in rat critical-sized calvarial defects.

Ultra-small BaGdF5-based upconversion nanoparticles as drug carriers and multimodal imaging probes

A new type of drug-delivery system (DDS) was constructed, in which the anti-cancer drug doxorubicin (DOX) was conjugated to the ultra-small sized (sub-10 nm) BaGdF5:Yb3+/Tm3+ based upconversion nanoparticles (UCNPs). This multifunctional DDS simultaneously possesses drug delivery and optical/magnetic/X-ray computed tomography imaging capabilities. The DOX can be selectively released by cleavage of hydrazone bonds in acidic environment, which shows a pH-triggered drug release behavior. The MTT assay shows these DOX-conjugated UCNPs exhibit obvious cytotoxic effect on HeLa cells. Moreover, to improve the upconversion luminescence intensity, core–shell structured UCNPs were constructed. The in vitro upconversion luminescence images of these UCNPs uptaken by HeLa cells show bright emission with high contrast. In addition, these UCNPs were further explored for T1-weighted magnetic resonance (MR) and X-ray computed tomography (CT) imaging in vitro. Long-term in vivo toxicity studies indicated that mice intravenously injected with 10 mg/kg of UCNPs survived for 40 days without any apparent adverse effects to their health. The results indicate that this multifunctional drug-delivery system with optimized size, excellent optical/MR/CT trimodal imaging capabilities, and pH-triggered drug release property is expected to be a promising platform for simultaneous cancer therapy and bioimaging.

Antioxidant properties of certain cereals as affected by food-grade bacteria fermentation

The effects of fermentation by 2 food-grade bacteria (Bacillus subtilis and Lactobacillus plantarum) on antioxidant activities and the contents of phenolics and flavonoids in 4 cereals (specifically adlay, chestnut, lotus seed, and walnut) were determined and compared with those of their non-fermented counterparts. Results showed that antioxidant properties observed in the fermented and non-fermented cereals may vary with fermented starters. Fermentation was observed to increase the phenolic and flavonoid contents of the extracts. The effects on Bacillus-fermented cereals were stronger than on Lactobacillus-fermented cereals. In IC50 values (mg/mL) of extracts, the extracts of fermented cereal showed a stronger DPPH radical scavenging and ferric-reducing activities. Fermentation did not significantly alter the Fe(2+)-chelating activity in the extracts of chestnuts and lotus seeds. All cereals were shown significantly inhibited the production of LPS-induced intracellular reactive oxygen species (ROS) without creating obvious cytotoxic effects in the macrophage cells. These results suggest that the fermentation process enables cereal-based foods with enhanced antioxidant capacities to contribute to health and nutritional improvements in consumers.

Purification and characterization of L-amino acid oxidase from the solid-state grown cultures of Aspergillus oryzae ASH

L-Amino acid oxidase (L-AAO) was purified from the solid state-grown cultures of A. oryzae ASH (JX006239.1) by fractional salting out, followed by ion exchange and gel filtration chromatography, to its molecular homogeneity, displaying 3.38-fold purification in comparison with the crude enzyme. SDS-PAGE revealed the enzyme to be a homo-dimer with ∼55-kDa subunits, with approximate molecular weight on native PAGE of 105–110 kDa. Two absorption maxima, at 280 nm and 341 nm, for the apoproteinic and FMN prosthetic group of the enzyme, respectively, were observed, with no detected surface glycosyl residues. The enzyme had maximum activity at pH 7.8–8.0, with ionic structural stability within pH range 7.2–7.6 and pH precipitation point (pI) 4.1–5.0. L-AAO exhibited the highest activity at 55°C, with plausible thermal stability below 40°C. The enzyme had T 1/2 values of 21.2, 8.3, 3.6, 3.1, 2.6 h at 30, 35, 40, 50, 60°C with Tm 61.3°C. Kinetically, A. oryzae L-AAO displayed a broad oxidative activity for tested amino acids as substrates. However, the enzyme had a higher affinity towards basic amino acid L-lysine (K m 3.3 mM, K cat 0.04 s−1) followed by aromatic amino acids L-tyrosine (K m 5.3 mM, K cat 0.036 s−1) and L-phenylalanine (K m 6.6 mM), with 1ow affinity for the S-amino acid L-methionine (K m 15.6 mM). The higher specificity of A. oryzae L-AAO to L-lysine as substrate seems to be a unique property comparing to this enzyme from other microbes. The enzyme was significantly inhibited by hydroxylamine and SDS, with slight inhibition by EDTA. The enzyme had a little effect on AST and ALT, with no effect on platelet aggregation and blood hemolysis in vivo with an obvious cytotoxic effect towards HepG2 (IC50 832.2 μg/mL) and MCF-7 (IC50, 370.6 μg/mL) tumor cells in vitro.

Cell response of nanographene platelets to human osteoblast‐like MG63 cells

The biologic/cytotoxic effects of dispersed nanographene platelets (NGPs) on human osteosarcoma cells (MG63 cell line) were first studied by examining cell viability, cycle, apoptosis, change in morphology, lactate dehydrogenase (LDH) release, alkaline phosphatase (ALP) activity, and inflammation. The results shown that the cell cytotoxicity of the dispersed NGPs exhibited dose-dependent characters, which had no obvious cytotoxic effects to MG63 cells at the concentration less than 10 μg mL(-1), whereas could postpone cell cycle, promote cell apoptosis, damage cell microstructure, induce serious tumor necrosis factor-α expression and greatly reduce ALP activity of MG63 cells at higher concentration of NGPs (>10 µg mL(-1)). Besides, NGPs had little influence on the LDH leakage. The cytotoxic mechanism of NGPs to MG63 cells was speculated to be intracellular activity with no physical damage of plasma membrane.

795 PROSTATE CANCER-TARGETED DELIVERY OF NANOMICELLE-LOADED WITH P110BETA-SPECIFIC INHIBITOR TGX221 PRO-DRUGS SUPPRESSES XENOGRAFT TUMOR GROWTH

You have accessJournal of UrologyProstate Cancer: Basic Research (IV)1 Apr 2013795 PROSTATE CANCER-TARGETED DELIVERY OF NANOMICELLE-LOADED WITH P110BETA-SPECIFIC INHIBITOR TGX221 PRO-DRUGS SUPPRESSES XENOGRAFT TUMOR GROWTH Zachary Hamilton, Xing Zeng, Ruibao Chen, Yunqi Zhao, Qiuhong Yang, Yan Huang, Laird Forrest, J. Brantley Thrasher, and Benyi Li Zachary HamiltonZachary Hamilton Kansas City, KS More articles by this author , Xing ZengXing Zeng Kansas City, KS More articles by this author , Ruibao ChenRuibao Chen Kansas City, KS More articles by this author , Yunqi ZhaoYunqi Zhao Lawrence, KS More articles by this author , Qiuhong YangQiuhong Yang Lawrence, KS More articles by this author , Yan HuangYan Huang Kansas City, KS More articles by this author , Laird ForrestLaird Forrest Lawrence, KS More articles by this author , J. Brantley ThrasherJ. Brantley Thrasher Kansas City, KS More articles by this author , and Benyi LiBenyi Li Kansas City, KS More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.359AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Early detection, radiation, surgery, and androgen deprivation therapy have made prostate cancer treatable for many patients; yet, it is the second leading cause of cancer death among American men. Recently, we demonstrated that PI3K p110beta isoform, a major cellular signaling molecule, is critical for prostate cancer progression in a cell culture model and a mouse xenograft model. In this study, we established a prostate-targeted delivery approach with p110beta-specific inhibitor TGX221 prodrug-loaded nano-micelle, in order to suppress growth of prostate cancer xenografts in vivo. METHODS We synthesized a TGX221 analog (pro-drug BL05-HA) that was integrated onto the nano-micelle polymers. The prostate specific membrane antigen (PSMA)-targeted RNA aptamer A10 was conjugated also onto the nano-micelles for prostate cancer cell targeting. Prostate cancer cell lines LNCaP, LAPC-4, C4-2 and 22RV1 were used in vitro for nanoparticle loading assay and in vivo to generate xenografts in nude mice (10 mice/group). Tumor growth was measured by length and width three days a week. Cell proliferation was assessed by immunohistochemistry (IHC) with anti-Ki67 antibody. AKT S473 phosphorylation was detected with IHC for evaluating the inhibitory effect on PI3K activity. RESULTS Our data demonstrated that BL05-HA pro-drug-loaded nano-micelles had no obvious cytotoxic effect on prostate cancer cells in vitro, possibly due to its slow releasing feature. BL05-HA loaded nano-micelles had better pharmacokinetics and superb tissue distribution in mouse prostate than the naked drug. There were no notable side-effects at a dose up to 100 mg/kg. This indicates that A10-based nano-micelle approach is a favorable formula for in vivo delivery of TGX221. Multiple experiments with different prostate cancer cell lines in nude mice also demonstrated a significant suppression of xenograft tumor growth in vivo. Further analysis revealed that TGX221 pro-drug dramatically reduced the Ki-67 index (cell proliferation) and AKT phosphorylation at S473, indicating the antitumor effect was due to suppression of p110beta activity. CONCLUSIONS Cell-based testing revealed that a significant inhibition of cell proliferation was achieved using the PSMA-targeting approach. An advantage of pharmacokinetics in nude mice was also observed. Prostate cancer-targeted nano-micelles loaded with p110beta specific inhibitor TGX221 pro-drug BL-05-HA is a promising novel agent for prostate cancer treatment, although further clinical trials are needed. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e327-e328 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zachary Hamilton Kansas City, KS More articles by this author Xing Zeng Kansas City, KS More articles by this author Ruibao Chen Kansas City, KS More articles by this author Yunqi Zhao Lawrence, KS More articles by this author Qiuhong Yang Lawrence, KS More articles by this author Yan Huang Kansas City, KS More articles by this author Laird Forrest Lawrence, KS More articles by this author J. Brantley Thrasher Kansas City, KS More articles by this author Benyi Li Kansas City, KS More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Anti-inflammatory activity of Lactobacillus-fermented adlay-soymilk in LPS-induced macrophages through suppression of NF-κB pathways

This study evaluated the anti-inflammatory activities of adlay-soymilk fermented with Lactobacillus plantarum in a lipopolysaccharide (LPS)-stimulated macrophage model. Both the adlay-soymilk (AS) and fermented adlay-soymilk (FA) significantly inhibited the production of LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), and intracellular reactive oxygen species (ROS) without creating obvious cytotoxic effects in the cells. Western blot analyses showed that AS and FA significantly blocked the protein expression of iNOS and COX-2 in LPS-induced macrophages. Moreover, AS and FA inhibited the activation of NF-κB and the production of LPS-induced TNF-α, IL-6, and IL-1β, in a concentration-dependent manner. The results showed that anti-inflammatory properties observed in FA and AS may vary with fermentation processing. Fermentation was observed to increase the anti-inflammatory properties of the adlay-soymilk. In conclusion, our study shows that the application of L. plantarum for FA production contributes anti-inflammatory effects by attenuating the generation of excessive NO, PGE2, and ROS, and by suppressing the expression of pro-inflammatory genes through inhibiting NF-κB activation, which could be serve as potential strategy in the prevention of inflammation-related diseases.

Inhibition of angiogenesis and invasion by DMBT is mediated by downregulation of VEGF and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells

Invasion, either directly or via metastasis formation, is the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. In order to obtain more potent inhibitors, a series of brartemicin analogs were synthesized and evaluated for their inhibitory activity against invasion. Among the synthetic analogs tested, DMBT, 6,6'-bis (2,3-dimethoxybenzoyl)-a,a-D-trehalose, was found to be the most potent anti-invasive agent. But the effects of DMBT on breast cancer cells were not known. In this study, the effects of DMBT on invasion and metastasis in MDA-MB-231 cells were investigated. MTT assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found. DMBT could inhibit invasion, migration and tube formation of HUVECs. Gelatin zymography showed that DMBT inhibited secretion and activity of MMP-9. Western blotting demonstrated that DMBT effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and p-Akt. These results suggested that DMBT could inhibit invasion and angiogenesis by downregulation of VEGF and MMP-9, resulting from the inhibition of Akt pathway. DMBT might be a promising lead molecule for the anti-metastasis and serve as a therapeutic agent to inhibit breast cancer cell invasion and metastasis.

BD750, a benzothiazole derivative, inhibits T cell proliferation by affecting the JAK3/STAT5 signalling pathway

A series of benzothiazole derivatives were screened for immunosuppressive activity; of these compounds BD750 was found to be the most effective immunosuppressant. The purpose of the current study was to determine the immunosuppressive activity of BD750 on T cell proliferation and its potential mode of action. T cell proliferation, CD25 and CD69 expression and cell cycle distribution were measured in vitro by flow cytometry. Cell viability was determined by CCK-8 assay. Cytokine levels were measured by elisa. The activation of signal-regulated molecules was assessed by Western blot analysis. The effects of BD750 were evaluated in vivo in a mouse model of delayed-type hypersensitivity. BD750 significantly inhibited mouse and human T cell proliferation, stimulated either by anti-CD3/anti-CD28 monoclonal antibodies or by an alloantigen, in a dose-dependent manner in vitro. No obvious cytotoxic effects of BD750 were observed in our experimental conditions. Furthermore, BD750 did not inhibit CD25 and CD69 expression or IL-2 and IL-4 secretion, but induced cell cycle arrest at the G(0) /G(1) phase in activated T cells. In IL-2-stimulated CTLL-2 cells and primary activated T cells, BD750 inhibited cell proliferation and STAT5 phosphorylation, but not Akt or p70S6K phosphorylation. BD750 also reduced the T cell-mediated delayed-type hypersensitivity response in mice in a dose-dependent manner. These data indicate that BD750 inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation. BD750 has the potential to be used as a lead compound for the design and development of new immunosuppressants for preventing graft rejection and treating autoimmune diseases.

Characterization of flavonoids from Dryopteris erythrosora and evaluation of their antioxidant, anticancer and acetylcholinesterase inhibition activities

The profiles and bioactivities of flavonoids extracted from Dryopteris erythrosora were investigated. The total flavonoid content in full plant of D. Erythrosora is about 14.33%. The main flavonoids in D. Erythrosora were identified as gliricidin 7-O-hexoside, apigenin7-O-glucoside, quercetin 7-O-rutinoside, quercetin 7-O-galactoside, keampferol 7-O-gentiobioside, keampferol-3-O-rutinoside, myricetin 3-O-rhamnoside and quercitrin by means of HPLC-DAD–ESI-MS. Flavonoids (0.36mg/ml) extract from D. erythrosora showed similar 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS), superoxide anion scavenging potential and ferric reducing antioxidant potential (FRAP) with that of rutin (0.80mg/ml). However, the antioxidant power by FRAP assay of 0.36mg/ml flavonoids extract from D. erythrosora was much weaker than that of 0.80mg/ml rutin. Moreover, the flavonoids extract from D. erythrosora showed obvious cytotoxic effects on A549 cells. The antioxidant activities of flavonoids extracts from 69 ferns showed a significant reciprocal proportion to the total flavonoids contents. The flavonoids extract from D. erythrosora exhibited a dose-dependent inhibition against acetylcholinesterase. Moreover, the anticancer activity slightly increased with improving antioxidant potential of fern flavonoids. Fern flavonoids are excellent function foods.

Doxorubicin conjugated NaYF4:Yb3+/Tm3+ nanoparticles for therapy and sensing of drug delivery by luminescence resonance energy transfer

In this study, we report an anticancer drug delivery system based on doxorubicin (DOX)-conjugated NaYF4:Yb3+/Tm3+ nanoparticles. The as-synthesized nanoparticles consist of uniform spherical nanoparticles with an average diameter of 25 nm. The drug delivery system demonstrates the ability to release DOX by cleavage of the hydrazone bond in mildly acidic environments. The spectra overlap between emission of donor NaYF4:Yb3+/Tm3+ nanoparticles at 452 nm (1D2→3F4) and 477 nm (1G4→3H6) and the broad absorbance of acceptor DOX centered at around 480 nm enables energy transfer to occur between the nanoparticles and DOX. The quenching and recovery of the up-conversion luminescence of NaYF4:Yb3+/Tm3+ by DOX due to luminescence resonance energy transfer (LRET) mechanism are applied as optical probe to confirm the DOX conjunction and monitor the release of DOX. The DOX-conjugated NaYF4:Yb3+/Tm3+ nanoparticles exhibit an obvious cytotoxic effect on SKOV3 ovarian cancer cells via MTT assay. Meanwhile, the endocytosis process of DOX-conjugated NaYF4:Yb3+/Tm3+ nanoparticles by SKVO3 cells was demonstrated through confocal laser scanning microscopy (CLSM), flow cytometry and ICP-OES. Such drug delivery system, which combines pH-triggered drug-release and up-converting nanoparticles-based LRET property, has excellent potential applications in cancer therapy and smart imaging.