The effects of tea extracts on proinflammatory signaling

BACKGROUND: Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin during radiotherapy exists. In this study, we explored the effect of topically-applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most-active moiety of green tea. METHODS: Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed retrospectively. Tea extracts were compared for their ability to modulate IL-1β, IL-6, IL-8, TNFα and PGE(2 )release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-κB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays. RESULTS: Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-κB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation CONCLUSION: Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate

Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.</p> <p>Methods</p> <p>Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. <it>In vivo </it>effect of EGCG on tumor growth was examined in a xenograft model.</p> <p>Results</p> <p>Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44°C for 1 h) or oxidative stress (H₂O₂, 500 μM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.</p> <p>Conclusions</p> <p>Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer.</p

Chromatographic Examinations of Tea's Protection Against Lipid Oxidative Modifications

Ethanol metabolism is accompanied by generation of free radicals that damage cell components, especially lipids. The present study was designed to investigate the efficacy of the preventive effect of black tea on the lipid oxidative modifications in different tissues (plasma, liver, brain, kidney, stomach, lung, intestine, and spleen) of 12-month-old rats chronically intoxicated with ethanol. Ethanol intoxication caused changes in the level/activity of antioxidants that led to the significant increase in the level of lipid oxidative modification products. Oxidative modifications were estimated by measuring lipid hydroperoxides, malondialdehyde, and 4-hydroxynonenal by high-performance liquid chromatography (HPLC) and by spectrophotometric determination of conjugated dienes. These lipid-modification marker levels were increased in almost all examined tissues (3%–71%) after ethanol intoxication. Described changes were in accordance with the liver level of the most often used marker of arachidonic acid oxidation, isoprostane (8-isoPGF2α), determined by the LC/MS system. Administration of black tea to ethanol-intoxicated rats remarkably prevents the significant increase (by about 15%–42%) in concentrations of all measured parameters regarding all examined tissues, but especially the plasma, liver, brain, stomach, and spleen. The preventive effect of black tea in the other organs (kidney, lung, intestine) caused a decrease in examined markers in a smaller degree (by about 7%–28%). To determine in the liver the major constituents of black tea mainly responsible for antioxidative action such as catechins and theaflavins, which were absorbed in organism, the present study indicates their protective effect against ethanol-induced oxidative modifications of lipids

A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer

Formation of Periodically Arranged Nanobubbles in Mesopores Capillary Bridge Formation and Cavitation during Sorption and Solidification in an Hierarchical Porous SBA 15 Matrix

We report synchrotron based small angle X ray scattering experiments on a template grown porous silica matrix Santa Barbara Amorphous 15 upon in situ sorption of fluorinated pentane C5F12 along with volumetric gas sorption isotherm measurements. Within the mean field model of Saam and Cole for vapor condensation in cylindrical pores, a nitrogen and C5F12 sorption isotherm is well described by a bimodal pore radius distribution dominated by meso and micropores with 3.4 and 1.6 nm mean radius, respectively. In the scattering experiments, two different periodicities become evident. One of them d1 11.5 nm reflects the next nearest neighbor distance in a 2D hexagonal lattice of tubular mesopores. A second periodicity d2 11.4 nm found during in situ sorption and freezing experiments is traced back to a superstructure along the cylindrical mesopores. It is compatible with periodic pore corrugations found in electron tomograms of empty SBA 15 by Gommes et al. Chem. Mater. 2009, 21, 1311 amp; 8722;1317 . A Rayleigh amp; 8722;Plateau instability occurring at the cylindrical blockcopolymer micelles characteristic of the SBA 15 templating process quantitatively accounts for the superstructure and thus the spatial periodicity of the pore wall corrugation. The consequences of this peculiar morphological feature on the spatial arrangement of C5F12, in particular the formation of periodically arranged nanobubbles or voids upon adsorption, desorption, and freezing of liquids, are discussed in terms of capillary bridge formation and cavitation in tubular but periodically corrugated pore

Silver substrates for surface enhanced Raman scattering: Correlation between nanostructure and Raman scattering enhancement

The fabrication of substrates for Surface Enhanced Raman Scattering (SERS) applications matching the needs for high sensitive and reproducible sensors remains a major scientific and technological issue. We correlate the morphological parameters of silver (Ag) nanostructured thin films prepared by sputter deposition on flat silicon (Si) substrates with their SERS activity. A maximum enhancement of the SERS signal has been found at the Ag percolation threshold, leading to the detection of thiophenol, a non-resonant Raman probe, at concentrations as low as 10-10M, which corresponds to enhancement factors higher than 7 orders of magnitude. To gain full control over the developed nanostructure, we employed the combination of in-situ time-resolved microfocus Grazing Incidence Small Angle X-ray Scattering with sputter deposition. This enables to achieve a deepened understanding of the different growth regimes of Ag. Thereby an improved tailoring of the thin film nanostructure for SERS applications can be realized. © 2014 AIP Publishing LLC.Peer Reviewe

An In-Situ µGISAXS Investigation of the Growth of Magnetic Nanostructures on Rippled Templates

Poster presented at the 16th International Conference on Small-Angle Scattering, held on 13-18th September, 2015, Berlin (Germany).Patterning of magnetic materials at nanoscale is so crucial for spintronic applications. The artificial tuning of magnetic properties of ultrathin films by means of the surface and interface modifications is a fascinating issue from both fundamental and technological points of view. Recently, nanorippled Si substrates produced by low energy ion beam erosion have been used as templates for growing nanostructured metallic thin films with tunable functional properties [1, 2]. The structure and the morphology of the nanopatterned substrate are expected to affect significantly the growth behavior of the metallic thin film, inducing anisotropy in the morphology. Therefore it is important to understand the effect of the structure and morphology of the nanopatterned substrate on the growth behavior of metallic thin films. In this work, investigation of the growth mechanism of magnetic thin films of Co and Permalloy (Ni80Fe20) deposited at normal incidence and glancing angle sputter geometry on nano-rippled Si (100) substrates using in-situ μGI-SAXS measurements has been done. We have performed in-situ real time μGISAXS at the P03/MiNaXS beamline [3, 4] of PETRA III storage ring during the sputter deposition thin films. Nanorippled Si substrates prepared by low energy ion beam sputtering with average wavelength of 40 nm and depth of 3 nm have been used as a template. A detailed investigation of the effect of various experimental parameters on the formation of patterned templates has been studied using GISAXS. The thickness of the deposited thin films has been calibrated by x-ray reflectivity measurements. In the case of Co thin film deposited at normal incidence the film replicates the morphology up to larger thickness regimes. It has been found that growth is highly anisotropic along and normal to the ripple wave vectors. Magnetic measurements show a strong uniaxial magnetic anisotropy with magnetization in a direction normal to the ripple wave vector. In the case of Permalloy thin films deposited at glancing angle, the shadowing effect leads to the formation of tilted nanowires. The conformity with the template has been observed for low thickness values and it gradually decreases with increasing the film thickness. Annealing followed by the deposition generates large range ordered nanowires. Also tried to correlate the observed magnetic anisotropy with anisotropic nanostructure deduced from GISAXS

Tailoring of uniaxial magnetic anisotropy in Permalloy thin films using nanorippled Si substrates

In this work the investigation of in-plane uniaxial magnetic anisotropy induced by the morphology due to ion beam erosion of Si(1 0 0) has been done. Ion beam erosion at an oblique angle of incidence generates a well-ordered nanoripple structure on the Si surface and ripple propagates in a direction normal to ion beam erosion. Permalloy thin films grown on such periodic nanopatterns show a strong uniaxial magnetic anisotropy with easy axis of magnetization in a direction normal to the ripple wave vector. The strength of uniaxial magnetic anisotropy is found to be high for the low value of ripple wavelength; it is decreasing with increasing value of ripple wavelength. Similarly, the strength of uniaxial magnetic anisotropy decreases with increasing Permalloy film thickness. Grazing incidence small angle x-ray scattering data reveals an anisotropic growth of Permalloy thin films with preferential orientation of grains in the direction normal to the ripple wave vector. Permalloy thin film growth is highly conformal with the film surface replicating the substrate ripple morphology up to a film thickness of 50 nm has been observed. Correlation between observed uniaxial magnetic anisotropy to surface modification has been addressed

Electronic excitation induced structural modification of FeCo nanoparticles embedded in silica matrix

Electronic excitation mediated energy loss by 120 MeV Au9+ swift heavy ions (SHIs) results in significant structural modifications of FeCo nanoparticles embedded in thin SiO2 matrix. The variations in local atomic structure and particle size/shape at different irradiation fluences are probed by extended x-ray absorption fine structure spectroscopy (EXAFS) and grazing incidence small angle x-ray scattering (GISAXS). The crystallinity and ordering of the films are found to first decrease and then increase with fluence. The observed alterations in co-ordination number of Fe/Co from EXAFS are correlated primarily with particle size modifications due to a transient thermal spike generated in the embedded nanoparticles by SHIs. The role of hydrogen desorption from nanoparticles is also highlighted