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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we screened a total of 201 diethyl ether, ethanol, and ethyl acetate fungal Basidiomycetes extracts for anti-androgenic activity. Based on our screened results in combination with the selective inhibition of prostate cancer LNCaP cells, we selected Coprinus comatus and Ganoderma lucidum for further evaluation. We demonstrated that ethanol and ethyl acetate extracts from C. comatus and G. lucidum, respectively, selectively inhibit dihydrotestosterone-induced LNCaP cell viability, suppress levels of secreted prostate-specific antigen in a dose-dependent manner, and cause a G1 phase arrest in LNCaP, but not in DU 145 and PC-3 cells. For the first time, to the best of our knowledge, we demonstrated that C. comatus and G. lucidum decreased androgen and glucocorticoide receptors transcriptional activity in breast cancer MDA-kb2 cells in a dose-dependent manner, and suppressed androgen receptor (AR) protein level in LNCaP and MDA-kb2 cells. Our findings suggest that AR and non-AR mediated mechanisms underlie the effects of C. comatus and G. lucidum.
Mol Biol Rep 2008 Jun
PMID:Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function in LNCaP prostate cancer cells. 1743 21

The brains of Alzheimer's disease (AD) patients are characterized by large deposits of amyloid beta peptide (Abeta). Abeta is known to increase free radical production in nerve cells, leading to cell death that is characterized by lipid peroxidation, free radical formation, protein oxi-dation, and DNA/RNA oxidation. In this study, we selected an extract of Gardenia jasminoides by screening, and investigated its ameliorating effects on Abeta-induced oxidative stress using PC12 cells. The effects of the extract were evaluated using the 2,7 -dichlorofluorescein diacetate (DCF-DA) assay and the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. To find the active component, the ethanol extract was partitioned with hexane, chloroform, and ethyl acetate, respectively, and the active component was purified by silica-gel column chromatography and HPLC. The results suggested that Gardenia jasminoides extract can reduce the cytotoxicity of Abeta in PC 12 cells, possibly by reducing oxidative stress.
Mol Cells 2007 Aug 31
PMID:Ameliorating effect of Gardenia jasminoides extract on amyloid beta peptide-induced neuronal cell deficit. 1784 5

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional profiling revealed that celastrol treatment induces a battery of oxidant defense genes in addition to heat shock genes. Celastrol activated the yeast Yap1 oxidant defense transcription factor via the carboxy-terminal redox center that responds to electrophilic compounds. Antioxidant response genes were likewise induced in mammalian cells, demonstrating that the activation of two major cell stress pathways by celastrol is conserved. We report that celastrol's biological effects, including inhibition of glucocorticoid receptor activity, can be blocked by the addition of excess free thiol, suggesting a chemical mechanism for biological activity based on modification of key reactive thiols by this natural product.
Mol Biol Cell 2008 Mar
PMID:Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule. 1819 79

Pancreatic cancer is an aggressive disease with multiple biochemical and genetic alterations. Thus, a single agent to hit one molecular target may not be sufficient to treat this disease. The purpose of this study is to identify a novel Hsp90 inhibitor to disrupt protein-protein interactions of Hsp90 and its cochaperones for down-regulating many oncogenes simultaneously against pancreatic cancer cells. Here, we reported that celastrol disrupted Hsp90-Cdc37 interaction in the superchaperone complex to exhibit antitumor activity in vitro and in vivo. Molecular docking and molecular dynamic simulations showed that celastrol blocked the critical interaction of Glu33 (Hsp90) and Arg167 (Cdc37). Immunoprecipitation confirmed that celastrol (10 micromol/L) disrupted the Hsp90-Cdc37 interaction in the pancreatic cancer cell line Panc-1. In contrast to classic Hsp90 inhibitor (geldanamycin), celastrol (0.1-100 micromol/L) did not interfere with ATP binding to Hsp90. However, celastrol (1-5 micromol/L) induced Hsp90 client protein degradation (Cdk4 and Akt) by 70% to 80% and increased Hsp70 expression by 12-fold. Celastrol induced apoptosis in vitro and significantly inhibited tumor growth in Panc-1 xenografts. Moreover, celastrol (3 mg/kg) effectively suppressed tumor metastasis by more than 80% in RIP1-Tag2 transgenic mouse model with pancreatic islet cell carcinogenesis. The data suggest that celastrol is a novel Hsp90 inhibitor to disrupt Hsp90-Cdc37 interaction against pancreatic cancer cells.
Mol Cancer Ther 2008 Jan
PMID:A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. 1820 19

Acrylamide (AA) is formed during heating of carbohydrate rich foods in the course of the Maillard reaction. AA has been classified as probably carcinogenic to humans. Storage experiments with roasted coffee have shown that AA levels decrease depending on storage time and temperature. In the present study the fate of AA lost during storage of roasted and ground (R&G) coffee was studied, using 14C-labeled AA as radiotracer. Radiolabel was measured in coffee brew, filter residue, and volatiles. In the brew, total (14)C-label decreased during storage of R&G coffee, while activity in the filter residue built up concomitantly. [2,3-14C]-AA (14C-AA) was the only 14C-related water extractable low molecular compound in the brew detected by radio-HPLC. No formation of volatile 14C-AA-related compounds was detected during storage and coffee brewing. Close to 90% of the radiolabel in the filter residue (spent R&G coffee, spent grounds) remained firmly bound to the matrix, largely resisting extraction by aqueous ammonia, ethyl acetate, chloroform, hexane, and sequential polyenzymatic digest. Furanthiols, which are abundant as aroma components in roasted coffee, have not been found to be involved in the formation of covalent AA adducts and thus do not contribute substantially to the decrease of AA during storage.
Mol Nutr Food Res 2008 May
PMID:Fate of 14C-acrylamide in roasted and ground coffee during storage. 1843 40

Previous work established the phytoestrogenicity of "unfermented"Cyclopia (honeybush) extracts. The current study investigated the phytoestrogenicity of four Cyclopia harvestings (M6-9) for preparation of extracts with enhanced phytoestrogenicity for benchmarking against commercial preparations. Two extracts, from M6 (C. subternata) and M7 (C. genistoides), were identified as most phytoestrogenic using estrogen receptor binding, an estrogen receptor response element containing promoter reporter assay, alkaline phosphatase activity, and E-screen. M6 and M7 were sequentially and non-sequentially extracted with five solvents of differing polarities. Additionally, two extracts were prepared in the traditional way of preparing a cup of honeybush tea. The resultant 22 extracts were evaluated for estrogenicity. Select extracts were analysed by high-pressure liquid chromatography (HPLC) and liquid chromatography mass spectrometry (LC-MS). The sequentially extracted M6 methanol extract (SM6Met) had the highest potency and the sequentially extracted M6 ethyl acetate extract (SM6EAc) had the highest efficacy of all the extracts. The HPLC results suggested enrichment of luteolin in SM6EAc and enrichment of an unidentified polyphenol in SM6Met. Benchmarking against four commercial phytoestrogenic preparations suggest that in terms of the assays used, Cyclopia extracts have comparable potency and efficacy to the commercial extracts and thus have potential as marketable phytoestrogenic nutraceuticals.
J Steroid Biochem Mol Biol 2008 Nov
PMID:Selective extraction of Cyclopia for enhanced in vitro phytoestrogenicity and benchmarking against commercial phytoestrogen extracts. 1879 25

Recently, we have identified a gene encoding a LuxR-type factor, TeiR (Testosterone-inducible Regulator), which positively regulates steroid degradation in Comamonas testosteroni. Herein, we demonstrate that TeiR interacts in vivo with steroid catabolic gene promoters. The presence of testosterone induces a significant TeiR protein increase at the early logarithmic phase of growth. Interestingly, it is not until the early stationary phase where the activation of a steroid-inducible gene promoter is observed, indicating that testosterone might not be the true inductor of the steroid degradation pathway. In addition, beta-galactosidase expression driven by a testosterone-inducible promoter is prematurely activated in cells cultured in medium supplemented with ethyl acetate extracts obtained from the early stationary phase cell-free supernatants of C. testosteroni grown in presence of testosterone. Complementation experiments of C. testosteroni wild type performed with teiR deletion constructs indicate that extra-copies of deleted-TeiR exert a dominant negative effect on the wild-type TeiR protein. While, when C. testosteroni teiR mutants were used to carry out complementation assays only the full length gene can overcome the teiR mutant phenotype. Altogether these findings indicate that TeiR regulates steroid catabolic genes interacting with their promoters and suggest that this interaction requires the presence of a testosterone-derived metabolite to induce the system.
J Steroid Biochem Mol Biol 2008 Nov
PMID:Regulation of testosterone degradation in Comamonas testosteroni. 1885 46

Oleuropein and (+)-cycloolivil are natural polyphenolic compounds with a significant radical scavenging activity present in olive tree. We have investigated the antiaggregant effects of oleuropein and (+)-cycloolivil isolated from an ethyl acetate extract of olive tree wood. Oleuropein and (+)-cycloolivil reduced the ability of thrombin to stimulate platelet aggregation. Both compounds reduced thrombin-evoked Ca(2+) release and entry to a similar extent to hydroxytyrosol. This effect was greater in platelets from patients with type 2 diabetes mellitus than in controls. Thrombin-, thapsigargin- and 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ)-evoked protein tyrosine phosphorylation, which is involved in Ca(2+) signalling and platelet aggregation, is inhibited by oleuropein and (+)-cycloolivil. oleuropein and (+)-cycloolivil are natural oxygen radical scavengers that reduce thrombin-induced protein tyrosine phosphorylation, Ca(2+) signalling and platelet aggregation. These observations suggest that oleuropein and (+)-cycloolivil may prevent thrombotic complications associated to platelet hyperaggregability and be the base for the development of antiaggregant therapeutic strategies.
Blood Cells Mol Dis
PMID:Olive tree wood phenolic compounds with human platelet antiaggregant properties. 1919 14

Hydrophobic polymer layers (3 microm) were spin-coated on Si or Ge plates and placed in a flow through gas chamber. FTIR reflection spectra of the layers were recorded showing the characteristic IR absorption bands of the polymer and the interference pattern generated by layered structure of the polymer film. Upon exposure of the polymer layer to gaseous analytes enrichment in the polymer film occurred. This was evidenced by the appearance of analyte specific absorption particular in the mid-IR part of the spectrum, as well as by a shift in the interference pattern across the whole spectrum. Qualitative information concerning the analyte was accessible in the mid-IR part of the spectrum, whereas quantitative assessment was obtained from the interference pattern. Polyetherurethane, polydimethylsiloxane, Makrolon and polyisobutylene polymer layers were tested for such IR-RIfS measurements, whereas toluene, o-dichlorobenzene, m-xylene, ethyl acetate and cyclohexane were employed as analytes. There was no influence of water vapour neither on the IR absorptions nor the interference pattern as hydrophobic polymers were used.
Spectrochim Acta A Mol Biomol Spectrosc 2009 Jun
PMID:IR absorption and reflectometric interference spectroscopy (RIfS) combined to a new sensing approach for gas analytes absorbed into thin polymer films. 1923 14

The 4-hydroxy benzaldehyde-N-methyl 4-stilbazolium tosylate (HBST), a good non-linear optical (NLO) crystal has been synthesized and the single crystal has been grown by slow evaporation method. In this work we have used ethyl acetate mixed methanol (1:1 ratio) as solvent. The lattice parameters were calculated from the powder X-ray diffraction patterns and compared with previous reports. The crystalline perfection has been verified with multicrystal X-ray diffractometer. The functional groups were identified from FTIR and NMR spectral studies. In order to know the optical quality of the grown crystal, the UV-Vis-NIR absorption spectrum was recorded and optical transition energy levels were also calculated. The thermal properties were analyzed from TG/DTA data. The relative SHG efficiency was compared with urea by Kurtz powder method.
Spectrochim Acta A Mol Biomol Spectrosc 2009 Jul
PMID:Growth and characterization of organic non-linear optical crystal 4-hydoroxy benzaldehyde-N-methyl 4-stilbazolium tosylate (HBST). 1925 77


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