ABSTRACT
In addition to potent anticancer effects of selenite, a modest therapeutic effect of sodium selenate has been demonstrated in prostate cancer patients. Selenate acts by activating protein phosphatase 2A, which inhibits various signal transduction cascades, including the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The human colorectal carcinoma cell line DLD-1 harbors a constitutive active mutation in PIK3CA encoding the PI3K p110α catalytic subunit. Thus, we examined the anticancer effect of sodium selenate in DLD-1 cells. As expected, selenate significantly decreased cell viability and increased apoptosis at a 50% inhibitory concentration (IC50) of 0.88mM, whereas selenite was much more potent at an IC50 of 0.0061mM. Surprisingly, at lower concentrations (0.04-0.16mM), selenate induced changes in cell morphology and motility that are characteristic of the epithelial-mesenchymal transition (EMT). Moreover, selenate-induced EMT was associated with AKT activation, increased expression of the EMT-inducing transcription factor TWIST1 and the mesenchymal cell-specific intermediate filament vimentin, and decreased expression of the epithelial cell-specific adhesion molecule E-cadherin. The critical role of AKT activation in selenate-induced EMT was identified using the AKT inhibitor Akti-1/2, which suppressed EMT-associated cell motility and invasion. These results suggest that although sodium selenate is a potential anticancer drug, deleterious effects of EMT induction should be taken into careful consideration.
Subject(s)
Antineoplastic Agents/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Oncogene Protein v-akt/metabolism , Selenium Compounds/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Enzyme Activation/physiology , Humans , Oncogene Protein v-akt/physiology , Osmolar Concentration , Selenic Acid , Up-Regulation/drug effectsABSTRACT
Bacteria were isolated from black lesions on shoots of European pear trees (Pyrus communis L.) in an orchard in Japan. Previous characterization of this novel pathogen by phenotypic and genotypic methods suggested that it should belong to the genus Erwinia but might not correspond to either Erwinia amylovora or Erwinia pyrifoliae. Here, phylogenetic analyses of the 16S rRNA gene, gyrB, and rpoD gene sequences indicated that it could not be assigned to any recognized species of the genus Erwinia. DNA-DNA hybridization confirmed that the bacterial strains represented a novel species. The DNA G+C contents, the fatty acid profile and phenotypic characteristics resembled those previously reported for members of the genus Erwinia. On the basis of these and previous results, the pathogen represents a novel species of the genus Erwinia, for which the name Erwinia uzenensis sp. nov. (type strain: YPPS 951(T)â=âLMG 25843(T)â=âNCPPB 4475(T)) is proposed.
Subject(s)
Erwinia/classification , Erwinia/isolation & purification , Phylogeny , Plant Diseases/microbiology , Pyrus/microbiology , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Erwinia/genetics , Fatty Acids/analysis , Genes, Bacterial , Japan , Molecular Sequence Data , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNAABSTRACT
Bacterial isolates from wild Agaricales fungi detoxified tolaasin, the inducer of brown blotch disease of cultivated mushrooms produced by Pseudomonas tolaasii. Mycetocola tolaasinivorans and Mycetocola lacteus were associated with fruit bodies of wild Pleurotus ostreatus and wild Lepista nuda, respectively. Tolaasin-detoxifying bacteria belonging to other genera were found in various wild mushrooms. An Acinetobacter sp. was isolated from fruit bodies of Tricholoma matsutake, Bacillus pumilus was isolated from Coprinus disseminatus, and Sphingobacterium multivorum was isolated from Clitocybe clavipes. A Pedobacter sp., which seemed not be identifiable as any known bacterial species, was isolated from a Clitocybe sp. Tolaasin-detoxifying bacteria identified thus far were attached to the surface of mycelia rather than residing within the fungal cells. M. tolaasinivorans, M. lacteus, B. pumilus, the Pedobacter sp., and S. multivorum efficiently detoxified tolaasin and strongly suppressed brown blotch development in cultivated P. ostreatus and Agaricus bisporus in vitro, but the Acinetobacter sp. did so less efficiently. These bacteria may be useful for the elucidation of mechanisms involved in tolaasin-detoxification, and may become biological control agents of mushroom disease.