Deuschle U.,Phenex Pharmaceuticals |
Schuler J.,Oncotest GmbH |
Schulz A.,Phenex Pharmaceuticals |
Schluter T.,Phenex Pharmaceuticals |
And 3 more authors.
The farnesoid X receptor (FXR) is expressed predominantly in tissues exposed to high levels of bile acids and controls bile acid and lipid homeostasis. FXR-/- mice develop hepatocellular carcinoma (HCC) and show an increased prevalence for intestinal malignancies, suggesting a role of FXR as a tumor suppressor in enterohepatic tissues. The N-myc downstream-regulated gene 2 (NDRG2) has been recognized as a tumor suppressor gene, which is downregulated in human hepatocellular carcinoma, colorectal carcinoma and many other malignancies. We show reduced NDRG2 mRNA in livers of FXR-/- mice compared to wild type mice and both, FXR and NDRG2 mRNAs, are reduced in human HCC compared to normal liver. Gene reporter assays and Chromatin Immunoprecipitation data support that FXR directly controls NDRG2 transcription via IR1-type element(s) identified in the first introns of the human, mouse and rat NDRG2 genes. NDRG2 mRNA was induced by non-steroidal FXR agonists in livers of mice and the magnitude of induction of NDRG2 mRNA in three different human hepatoma cell lines was increased when ectopically expressing human FXR. Growth and metastasis of SK-Hep-1 cells was strongly reduced by non-steroidal FXR agonists in an orthotopic liver xenograft tumor model. Ectopic expression of FXR in SK-Hep1 cells reduced tumor growth and metastasis potential of corresponding cells and increased the anti-tumor efficacy of FXR agonists, which may be partly mediated via increased NDRG2 expression. FXR agonists may show a potential in the prevention and/or treatment of human hepatocellular carcinoma, a devastating malignancy with increasing prevalence and limited therapeutic options. © 2012 Deuschle et al. Source
Meyer H.,University of Greifswald |
Weidmann H.,University of Greifswald |
Weidmann H.,Oncotest GmbH |
Lalk M.,University of Greifswald
Microbial Cell Factories
Background: Bacillus subtilis (B. subtilis) has become widely accepted as a model organism for studies on Gram-positive bacteria. A deeper insight into the physiology of this prokaryote requires advanced studies of its metabolism. To provide a reliable basis for metabolome investigations, a validated experimental protocol is needed since the quality of the analytical sample and the final data are strongly affected by the sampling steps. To ensure that the sample analyzed precisely reflects the biological condition of interest, outside biases have to be avoided during sample preparation.Results: Procedures for sampling, quenching, extraction of metabolites, cell disruption, as well as metabolite leakage were tested and optimized for B. subtilis. In particular the energy status of the bacterial cell, characterized by the adenylate energy charge, was used to evaluate sampling accuracy. Moreover, the results of the present study demonstrate that the cultivation medium can affect the efficiency of the developed sampling procedure.Conclusion: The final workflow presented here allows for the reproducible and reliable generation of physiological data. The method with the highest qualitative and quantitative metabolite yield was chosen, and when used together with complementary bioanalytical methods (i.e., GC-MS, LC-MS and 1H-NMR) provides a solid basis to gather information on the metabolome of B. subtilis. © 2013 Meyer et al.; licensee BioMed Central Ltd. Source
Oncotest Gmbh and PIRAMAL LIFE science Ltd | Date: 2010-11-15
Oncotest Gmbh and PIRAMAL ENTERPRISES Ltd | Date: 2011-08-05
This invention relates to purified compound of formula (1). The invention includes all isomeric forms and all tautomeric forms of the compound of formula (1) and pharmaceutically acceptable salts thereof. The present invention further relates to processes for the production of the compound of formula (1) by fermentation of the fungal strain of sterile mycelium (PM0509732/MTCC5544) and to pharmaceutical compositions containing the compound as active ingredient and its use in medicines for treatment of cancer.
Ding L.,Leibniz Institute for Natural Product Research and Infection Biology |
Maier A.,Oncotest GmbH |
Fiebig H.-H.,Oncotest GmbH |
Lin W.-H.,Peking University |
And 2 more authors.
Organic and Biomolecular Chemistry
Three novel indolosesquiterpenes, xiamycin B (1b), indosespene (2), and sespenine (3), along with the known xiamycin A (1a) were isolated from the culture broth of Streptomyces sp. HKI0595, a bacterial endophyte of the widespread mangrove tree Kandelia candel. Agar diffusion assays revealed moderate to strong antimicrobial activities against several bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, while no cytotoxicity against human tumor cell lines was observed. Together with the previously reported oridamycin, the endophyte metabolites represent the first indolosesquiterpenes isolated from prokaryotes. © 2011 The Royal Society of Chemistry. Source