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  • PROTEIN  (18)
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  • 1
    Keywords: brain ; RECEPTOR ; CELLS ; tumor ; Germany ; human ; SYSTEM ; SITE ; GENE ; PROTEIN ; RELEASE ; kidney ; LINKAGE ; TRANSPORT ; NERVOUS-SYSTEM ; resistance ; MUTATIONS ; LOCALIZATION ; MULTIDRUG-RESISTANCE PROTEIN ; ATP-dependent transport ; CONJUGATE EXPORT PUMP ; SUBSTRATE-SPECIFICITY ; GLIOMAS ; EFFLUX ; DISORDERS ; RE ; VESICLES ; CEREBELLAR NEURONS ; BASOLATERAL HEPATOCYTE MEMBRANE ; human brain ; BINDING CASSETTE TRANSPORTER ; multidrug resistance protein ; function ; DEHYDROEPIANDROSTERONE-SULFATE ; de-hydroepiandrosterone 3-sulfate ; GABA(A) receptor modulation ; GABA-A RECEPTOR ; multidrug resistance proteins ; NEUROACTIVE STEROIDS ; neuron ; neurosteroids ; paroxysmal kinesigenic choreoathetosis ; MULTIDRUG-RESISTANCE-PROTEIN
    Abstract: Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a K-m value of 21 mu M. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders. (c) 2005 Published by Elsevier Ltd on behalf of IBRO
    Type of Publication: Journal article published
    PubMed ID: 16359813
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  • 2
    Keywords: brain ; APOPTOSIS ; CELLS ; EXPRESSION ; IN-VITRO ; tumor ; CELL ; Germany ; human ; IN-VIVO ; INHIBITION ; KINASE ; PATHWAY ; VITRO ; PROTEIN ; RNA ; TUMORS ; BIOLOGY ; MOLECULAR-BIOLOGY ; PHOSPHORYLATION ; resistance ; genetics ; CANCER-CELLS ; ONCOGENE ; GLUCOSE ; OVEREXPRESSION ; heredity ; MAP KINASES ; INTEGRIN ACTIVATION ; signaling ; molecular biology ; molecular ; ONCOLOGY ; RE ; BRAIN-TUMORS ; GLIOMA ; GLIOMA-CELLS ; TRANSPORTER ; brain tumors ; LEVEL ; analysis ; PHOSPHOPROTEIN ; ENGLAND ; GLIOBLASTOMA ; ASTROCYTES ; CYTOPLASMIC SEQUESTRATION ; DEATH EFFECTOR DOMAIN ; ERK1/2 ; PEA-15/PED ; PED/PEA-15
    Abstract: PEA-15 ( phosphoprotein enriched in astrocytes 15 kDa) is a death effector domain-containing protein, which is involved in the regulation of apoptotic cell death. Since PEA-15 is highly expressed in cells of glia l origin, we studied the role of PEA-15 in human malignant brain tumors. Immunohistochemical analysis of PEA-15 expression shows strong immunoreactivity in astrocytomas and glioblastomas. Phosphorylation of PEA-15 at Ser(116) is found in vivo in perinecrotic areas in glioblastomas and in vitro after glucose deprivation of glioblastoma cells. Overexpression of PEA-15 induces a marked resistance against glucose deprivation-induced apoptosis, whereas small interfering RNA (siRNA)-mediated downregulation of endogenous PEA-15 results in the sensitization to glucose withdrawal-mediated cell death. This antiapoptotic activity of PEA-15 under low glucose conditions depends on its phosphorylation at Ser116. Moreover, siRNA-mediated knockdown of PEA-15 abolishes the tumorigenicity of U87MG glioblastoma cells in vivo. PEA-15 regulates the level of phosphorylated extracellular-regulated kinase ( ERK) 1/ 2 in glioblastoma cells and the PEA-15-dependent protection from glucose deprivation-induced cell death requires ERK1/2 signaling. PEA-15 transcriptionally upregulates the Glucose Transporter 3, which is abrogated by the inhibition of ERK1/2 phosphorylation. Taken together, our findings suggest that Ser(116)-phosphorylated PEA-15 renders glioma cells resistant to glucose deprivation-mediated cell death as encountered in poor microenvironments, for example in perinecrotic areas of glioblastomas
    Type of Publication: Journal article published
    PubMed ID: 17700518
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  • 3
    Keywords: brain ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; tumor ; CELL ; Germany ; LUNG-CANCER ; SYSTEM ; DISEASE ; PROTEIN ; TISSUE ; MICE ; PATIENT ; ANTIGEN ; T-CELL ; T-CELLS ; BONE-MARROW ; MEMORY ; RECOGNITION ; MOUSE ; IDENTIFICATION ; LYMPHOMA ; EFFICACY ; MELANOMA ; MASS-SPECTROMETRY ; HEAD ; NECK ; EPITOPE ; IMMUNOTHERAPY ; IMMUNOGENICITY ; CANCER PATIENTS ; CALCIUM-BINDING PROTEINS ; TUMOR-ASSOCIATED ANTIGENS ; NECK-CANCER ; brain tumor ; head and neck cancer ; endothelial cells ; proteome ; EGFR ; SEPARATION ; EXPRESSION PROFILES ; Type ; HEAD-AND-NECK
    Abstract: Identifying the antigens that have the potential to trigger endogenous antitumor responses in an individual cancer patient is likely to enhance the efficacy of cancer immunotherapy, but current methodologies do not efficiently identify such antigens. This study describes what we believe to be a new method of comprehensively identifying candidate tissue antigens that spontaneously cause T cell responses in disease situations. We used the newly developed automated, two-dimensional chromatography system PF2D to fractionate the proteome of human tumor tissues and tested protein fractions for recognition by preexisting tumor-specific CD4(+) Th cells and CTLs. Applying this method using mice transgenic for a TCR that recognizes an OVA peptide presented by MHC class I, we demonstrated efficient separation, processing, and cross-presentation to CD8(+) T cells by DCs of OVA expressed by the OVA-transfected mouse lymphoma RMA-OVA. Applying this method to human tumor tissues, we identified MUC1 and EGFR as tumor-associated antigens selectively recognized by T cells in patients with head and neck cancer. Finally, in an exemplary patient with a malignant brain tumor, we detected CD4(+) and CD8(+) T cell responses against two novel antigens, transthyretin and calgranulin B/S100A9, which were expressed in tumor and endothelial cells. The immunogenicity of these antigens was confirmed in 4 of 10 other brain tumor patients. This fast and inexpensive method therefore appears suitable for identifying candidate T cell antigens in various disease situations, such as autoimmune and malignant diseases, without being restricted to expression by a certain cell type or HLA allele
    Type of Publication: Journal article published
    PubMed ID: 20458140
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  • 4
    Keywords: brain ; APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; INHIBITOR ; proliferation ; tumor ; CELL ; CELL-PROLIFERATION ; Germany ; INHIBITION ; MODEL ; PATHWAY ; PATHWAYS ; THERAPY ; VITRO ; EXPOSURE ; GENE ; microarray ; PROTEIN ; RNA ; DIFFERENTIATION ; MECHANISM ; INDUCTION ; mechanisms ; BIOLOGY ; ACID ; TARGET ; PROGRESSION ; AMPLIFICATION ; ASSAY ; PROMOTER ; genetics ; ONCOGENE ; STEM-CELLS ; PROGENITOR CELLS ; CANCER-THERAPY ; GLIOMAS ; RETINOIC ACID ; TRANS-RETINOIC ACID ; INHIBITORS ; signaling ; ONCOLOGY ; GLIOMA ; GLIOMA-CELLS ; MOLECULAR-MECHANISMS ; LOCUS ; GLIOBLASTOMA ; MicroRNAs ; MICRORNA ; CELL BIOLOGY ; TUMOR-INITIATING CELLS ; Genetic ; tumor grade ; Molecular mechanisms ; CTGF ; miR-17-92 ; NEURAL PRECURSORS ; spheroid culture
    Abstract: All-trans retinoic acid is a potent promoter of cellular differentiation processes, which is used in cancer therapy. Glioblastoma spheroid cultures are enriched in tumor-initiating cells, and provide a model to test new treatment options in vitro. We investigated the molecular mechanisms of response to exposure to differentiation-promoting conditions in such cultures. Microarray analyses of five independent cultures showed that after induction of differentiation, inhibitors of transforming growth factor beta/bone morphogenetic protein, Wnt/beta-catenin and IGF signaling were upregulated, whereas expression of several microRNAs decreased, particularly that of the miR-17-92 cluster. In primary astrocytic gliomas (n = 82), expression of several members of miR-17-92 was significantly higher relative to those of normal brain (n = 8) and significantly increased with tumor grade progression (P 〈 0.05). A high-level amplification of the miR-17-92 locus was detected in one glioblastoma specimen. Transfection of inhibitors of miR-17-92 induced increased apoptosis and decreased cell proliferation in glioblastoma spheroids. Mir-17-92 inhibition was also associated with increased messenger RNA (mRNA) and/or protein expression of CDKN1A, E2F1, PTEN and CTGF. The CTGF gene was shown to be a target of miR-17-92 in glioblastoma spheroids by luciferase reporter assays. Our results suggest that miR-17-92 and its target CTGF mediate effects of differentiation-promoting treatment on glioblastoma cells through multiple regulatory pathways. Oncogene (2010) 29, 3411-3422; doi:10.1038/onc.2010.83; published online 22 March 2010
    Type of Publication: Journal article published
    PubMed ID: 20305691
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  • 5
    Keywords: GENES ; PROTEIN ; NEURAL STEM-CELLS ; SUBVENTRICULAR ZONE ; EXPANSION ; MAMMALIAN BRAIN ; CHARGE-SYNDROME ; DE-NOVO MUTATIONS ; ANALYSIS REVEALS ; NUCLEAR RECEPTOR TAILLESS
    Abstract: Chromatin factors that regulate neurogenesis in the central nervous system remain to be explored. Here, we demonstrate that the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7), a protein frequently mutated in human CHARGE syndrome, is a master regulator of neurogenesis in mammalian brain. CHD7 is selectively expressed in actively dividing neural stem cells (NSCs) and progenitors. Genetic inactivation of CHD7 in NSCs leads to a reduction of neuronal differentiation and aberrant dendritic development of newborn neurons. Strikingly, physical exercise can rescue the CHD7 mutant phenotype in the adult hippocampal dentate gyrus. We further show that in NSCs, CHD7 stimulates the expression of Sox4 and Sox11 genes via remodeling their promoters to an open chromatin state. Our study demonstrates an essential role of CHD7 in activation of the neuronal differentiation program in NSCs, thus providing insights into epigenetic regulation of stem cell differentiation and molecular mechanism of human CHARGE syndrome.
    Type of Publication: Journal article published
    PubMed ID: 23827709
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  • 6
    Keywords: brain ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; tumor ; CELL ; Germany ; human ; MICROSCOPY ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; DRUG ; FAMILY ; MEMBER ; MEMBERS ; GLYCOPROTEIN ; NO ; GLUTATHIONE ; resistance ; MEMBRANE ; NUCLEOTIDES ; REGION ; REGIONS ; LOCALIZATION ; POLYMERASE-CHAIN-REACTION ; CHAIN-REACTION ; DRUG-RESISTANCE ; MULTIDRUG-RESISTANCE ; CONJUGATE EXPORT PUMP ; ORGANIC ANION TRANSPORTER ; CHAIN ; quantitative polymerase chain reaction ; ADULT ; polymerase chain reaction ; P-GLYCOPROTEIN ; TRANSPORTER ; NEURONS ; GLYCOPROTEINS ; BASOLATERAL HEPATOCYTE MEMBRANE ; blood-brain barrier ; CEREBROSPINAL FLUID BARRIER ; CULTURED RAT ASTROCYTES ; human brain ; MICROVESSEL ENDOTHELIAL-CELLS ; MRP4 CONFERS RESISTANCE ; multidrug resistance proteins (MRPs,symbol ABCC) ; NORMAL HUMAN-TISSUES ; organic anions
    Abstract: Multidrug resistance proteins (MRPs, symbol ABCC) are membrane glycoproteins that mediate the ATP-dependent export of organic anions, including cytotoxic and antiviral drugs, from cells. To identify MRP family members possibly involved in the intrinsic resistance of human brain to cytotoxic and antiviral drugs, we analyzed the expression and localization of MRP1-MRP6 in rapidly frozen perilesional samples of several regions of adult human brain obtained during neurosurgery. Quantitative polymerase chain reaction analysis showed expression of MRP1, MRP2, MRP3, MRP4, and MRP5 mRNA, whereas MRP6 mRNA was below detectability. However, immunofluorescence microscopy of cryosections from human brain showed no reactivity for the MRP2 or MRP3 proteins. The proteins MRP1, MRP4, and MRP5 were clearly localized by confocal laser scanning microscopy to the luminal side of brain capillary endothelial cells. The MRP4 and MRP5 proteins were also detected in astrocytes of the subcortical white matter. Notably, MRP5 protein was present in pyramidal neurons. MRP proteins may, thus, contribute to the cellular efflux of endogenous anionic glutathione or glucuronate conjugates (substrates for MRP1), cyclic nucleotides (substrates for MRP4 and MRP5), or glutathione (co-substrate for MRP1 and MRP4); in addition, they may play an important role in the resistance of the brain to several cytotoxic and antiviral drugs. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15501592
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  • 7
    Keywords: brain ; RECEPTOR ; EXPRESSION ; tumor ; Germany ; neoplasms ; THERAPY ; SYSTEM ; DISTINCT ; PROTEIN ; TUMORS ; PATIENT ; DNA ; MECHANISM ; MARKER ; IMPACT ; prognosis ; FREQUENCY ; FREQUENCIES ; NERVOUS-SYSTEM ; IDENTIFICATION ; immunohistochemistry ; REPAIR ; inactivation ; PATHOGENESIS ; FRAMESHIFT MUTATIONS ; INSTABILITY ; microsatellite instability ; PHENOTYPE ; CARCINOMAS ; pathology ; NONPOLYPOSIS COLORECTAL-CANCER ; protein expression ; YOUNG ; DEFICIENCY ; FEATURES ; ENDOMETRIAL ; GLIOMA ; TARGET GENES ; analysis ; function ; LOSSES ; central nervous system ; COLON ADENOMAS ; TUMOR-SPECIFIC ANTIGENS
    Abstract: About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (similar to 25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms
    Type of Publication: Journal article published
    PubMed ID: 17388945
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  • 8
    Keywords: brain ; PEPTIDE ; APOPTOSIS ; CANCER ; CELLS ; GROWTH ; IN-VITRO ; INHIBITOR ; INVASION ; tumor ; TUMOR-CELLS ; CELL ; Germany ; human ; IN-VIVO ; INHIBITION ; KINASE ; VITRO ; VIVO ; DEATH ; DISTINCT ; PROTEIN ; RNA ; TUMORS ; ACTIVATION ; BIOLOGY ; DOWN-REGULATION ; treatment ; CLEAVAGE ; ASSAY ; resistance ; CELL-DEATH ; INDUCED APOPTOSIS ; DECREASE ; STRESS ; RESECTION ; CANCER-CELLS ; MIGRATION ; STRATEGIES ; CONSTITUTIVE ACTIVATION ; CASPASE 8 ; CROSS-TALK ; CD95 ; CASPASE ; INHIBITORS ; signaling ; ONCOLOGY ; RE ; PATTERN ; BRAIN-TUMORS ; GLIOMA ; GLIOMA-CELLS ; MALIGNANT GLIOMAS ; CASPASE-8 ; ASSAYS ; cell death ; PROMOTION ; USA ; caspases ; focal adhesion kinase ; gelsolin ; cancer research ; in vivo ; MOTILITY ; GLIOBLASTOMA ; PROMOTES ; apoptotic ; caspase-3 ; block ; SMALL INTERFERING RNA ; SECONDARY GLIOBLASTOMAS ; CELLULAR-RESISTANCE ; RADIOCHEMOTHERAPY
    Abstract: Glioblastomas, the most malignant of all brain tumors, are characterized by cellular resistance to apoptosis and a highly invasive growth pattern. These factors contribute to the poor response of glioblastomas to radiochemotherapy and prevent their complete neurosurgical resection. However, the driving force behind the distinct motility of glioma cells is only partly understood. Here, we report that in the absence of cellular stress and proapoptotic stimuli, human glioblastoma cells exhibit a constitutive activation of caspases in vivo and in vitro. The inhibition of caspases by various peptide inhibitors decreases the migration of cells in scrape motility assays and the invasiveness of cells in spheroid assays. Similarly, specific small interfering RNA- or antisense-mediated down-regulation of caspase-3 and caspase-8 results in an inhibition of the migratory potential of glioma cells. The constitutive caspase-dependent motility of glioblastoma cells is independent of CD95 activation and it is not mediated by mitogen-activated protein/ extracellular signal-regulated kinase kinase signaling. The basal caspase activity is accompanied by a constant cleavage of the motility-associated gelsolin protein, which may contribute to the caspase-mediated promotion of migration and invasiveness in glioblastoma cells. Our results suggest that the administration of low doses of caspase inhibitors that block glioma cell motility without affecting the execution of apoptotic cell death may be exploited as a novel strategy for the treatment of glioblastomas
    Type of Publication: Journal article published
    PubMed ID: 18171980
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  • 9
    Keywords: brain ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; IN-VITRO ; CELL ; Germany ; human ; MODEL ; VITRO ; GENE ; GENES ; PROTEIN ; cell line ; TISSUE ; MARKER ; BIOLOGY ; E7 ; immunohistochemistry ; resistance ; CELL-LINE ; LINE ; human papillomavirus ; E6 ; HUMAN-PAPILLOMAVIRUS ; MORPHOLOGY ; BARRIER FUNCTION ; TIGHT JUNCTIONS ; CONJUGATE EXPORT PUMP ; MRP2 ; ORIGIN ; RE ; TRANSFECTION ; P-GLYCOPROTEIN ; blood-brain barrier ; human brain ; ENDOTHELIAL-CELL ; brain capillary endothelial cell ; ATP-BINDING ; BLOOD-BRAIN ; ABC-TRANSPORTERS ; DRUG EFFLUX TRANSPORTERS ; endothelial markers
    Abstract: Primary human brain capillary endothelial cells (hBCECs) are available only in small quantities and have a short life span in vitro; this restricts their use as in vitro model for the blood-brain barrier (BBB). To overcome these limitations, we have established an immortalized hBCEC line (NKIM-6) by transfection with pLXSN16-E6E7, which encodes the human papillomavirus type 16 E6 and E7 genes. The cell line exhibits an extended life span in vitro and retains its characteristic endothelial morphology, endothelial markers, and physiology. Likewise, as demonstrated by immunohistochemistry and reverse transcription/polymerase chain reaction (RT-PCR), NKIM-6 cells express BBB markers, and the lack of glial, neuronal, and epithelial markers confirms their endothelial origin. Moreover, with quantitative RT-PCR, we have been able to demonstrate that several ATP-binding cassette-transporters are expressed in NKIM-6 cells with a conserved expression order compared with primary hBCECs. Our results suggest that this cell line might be suitable as in vitro model for several aspects of the BBB
    Type of Publication: Journal article published
    PubMed ID: 17180596
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  • 10
    Keywords: APOPTOSIS ; CANCER ; CELLS ; INHIBITOR ; tumor ; CELL ; Germany ; human ; IN-VIVO ; INHIBITION ; KINASE ; PATHWAY ; THERAPY ; DEATH ; PROTEIN ; PROTEINS ; DRUG ; LINES ; ACTIVATION ; LIGAND ; MECHANISM ; FAMILY ; REDUCTION ; INDUCTION ; CONTRAST ; CELL-LINES ; DOWN-REGULATION ; MEMBERS ; SUPPRESSION ; CLEAVAGE ; resistance ; CELL-LINE ; LINE ; STABILITY ; DEGRADATION ; DIETARY ; OVEREXPRESSION ; CANCER-THERAPY ; TRAIL ; AKT ; Bcl-2 ; RAT-BRAIN ; APOPTOSIS-INDUCING LIGAND ; CASPASE-8 ACTIVATION ; ONCOLOGY ; FAMILIES ; THERAPIES ; cancer therapy ; GLIOMA ; GLIOMA-CELLS ; human glioma ; CASPASE-8 ; SURVIVIN ; LEVEL ; INDUCE ; USA ; cancer research ; BCL-XL ; MCL-1 ; APO2L/TRAIL ; NOV ; BCL-2 FAMILY ; LIMITS ; proteasomal degradation ; TRAIL/Apo2L ; DRIVEN ; flavonoid ; glioma cell ; XIAP
    Abstract: Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) limits its potential as a drug for cancer therapy. Here, we report that kaempferol, a bioactive plant flavonoid, sensitizes U251 and U87 glioma cells to TRAIL-mediated apoptosis. In contrast, U373 cells are not affected by kaempferol treatment. Treatment of kaempferol alone for 24 h did not induce apoptosis in the cell lines. We provide evidence that TRAIL-induced apoptosis is partially driven by kaempferol-mediated reduction of survivin protein levels. On kaempferol treatment, proteasomal degradation of survivin was observed. Inhibition of proteasomal degradation with MG132 in kaempferol-treated cells restored survivin protein levels in both glial cell lines. Consequently, overexpression of survivin attenuated TRAIL-kaempferol-induced apoptosis. In addition, we show that kaempferol mediates down-regulation of phosphorylated Akt, thereby further reducing survivin protein level. Furthermore, the blockage of the serine/threonine kinase Akt activity by kaempferol is important for inhibition of survivin because active phosphorylated Akt enhances the stability of survivin. However, we also show that the combined treatment of TRAIL and kaempferol induces cleavage (activation) of caspase-8, thereby exerting a proapoptotic effect independent of survivin known not to inhibit caspase-8 activation. Other effects induced by kaempferol were suppression of X-linked inhibitor of apoptosis proteins as the antiapoptotic members of the Bcl-2 family, Bcl-2, Bcl-xL, and Mcl-1 in a concentration-dependent manner. In summary, we showed that suppression of survivin is an essential mechanism in TRAIL-kaempferol-mediated apoptosis. [Mol Cancer Ther 2008;7(11):3566-74]
    Type of Publication: Journal article published
    PubMed ID: 19001439
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