The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Zhujun Wang - One of the best experts on this subject based on the ideXlab platform.
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flavones and flavonols exert cytotoxic effects on a human oesophageal Adenocarcinoma Cell Line oe33 by causing g2 m arrest and inducing apoptosis
Food and Chemical Toxicology, 2008Co-Authors: Qiang Zhang, Xinhuai Zhao, Zhujun WangAbstract:Abstract Dietary flavonoids have been shown to exert specific cytotoxicity towards some cancer Cells, but the precise molecular mechanisms are still not completely understood. In our study, cytotoxic effects of structurally related flavones and flavonols on a human oesophageal Adenocarcinoma Cell Line (OE33) were compared, and the molecular mechanisms responsible for their cytotoxic effects were explored. The results of MTT assay showed that flavones (luteolin, apigenin, chrysin) and flavonols (quercetin, kaempferol, myricetin) were all able to induce cytotoxicity in OE33 Cells in a dose- and time-dependent manner, and the cytotoxic potency of these compounds was in the order of quercetin > luteolin > chrysin > kaempferol > apigenin > myricetin. Flow cytometry and DNA fragmentation analysis indicated that the cytotoxicity induced by flavones and flavonols was mediated by G2/M Cell cycle arrest and apoptosis. Furthermore, the expression of genes related to Cell cycle arrest and apoptosis was assessed by oligonucleotide microarray, real-time RT-PCR and Western blot. It was found that the treatment of OE33 Cells with flavones and flavonols caused G2/M arrest through up-regulation of GADD45β and 14-3-3σ and down-regulation of cyclin B1 at the mRNA and protein levels, and induced p53-independent mitochondrial-mediated apoptosis through up-regulation of PIG3 and cleavage of caspase-9 and caspase-3. The results of western blot analysis further showed that increases of p63 and p73 protein translation or stability might be contribute to the regulation of GADD45β, 14-3-3σ, cyclin B1 and PIG3.
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flavones and flavonols exert cytotoxic effects on a human oesophageal Adenocarcinoma Cell Line oe33 by causing g2 m arrest and inducing apoptosis
Food and Chemical Toxicology, 2008Co-Authors: Qiang Zhang, Xinhuai Zhao, Zhujun WangAbstract:Dietary flavonoids have been shown to exert specific cytotoxicity towards some cancer Cells, but the precise molecular mechanisms are still not completely understood. In our study, cytotoxic effects of structurally related flavones and flavonols on a human oesophageal Adenocarcinoma Cell Line (OE33) were compared, and the molecular mechanisms responsible for their cytotoxic effects were explored. The results of MTT assay showed that flavones (luteolin, apigenin, chrysin) and flavonols (quercetin, kaempferol, myricetin) were all able to induce cytotoxicity in OE33 Cells in a dose- and time-dependent manner, and the cytotoxic potency of these compounds was in the order of quercetin>luteolin>chrysin>kaempferol>apigenin>myricetin. Flow cytometry and DNA fragmentation analysis indicated that the cytotoxicity induced by flavones and flavonols was mediated by G2/M Cell cycle arrest and apoptosis. Furthermore, the expression of genes related to Cell cycle arrest and apoptosis was assessed by oligonucleotide microarray, real-time RT-PCR and Western blot. It was found that the treatment of OE33 Cells with flavones and flavonols caused G2/M arrest through up-regulation of GADD45beta and 14-3-3sigma and down-regulation of cyclin B1 at the mRNA and protein levels, and induced p53-independent mitochondrial-mediated apoptosis through up-regulation of PIG3 and cleavage of caspase-9 and caspase-3. The results of western blot analysis further showed that increases of p63 and p73 protein translation or stability might be contribute to the regulation of GADD45beta, 14-3-3sigma, cyclin B1 and PIG3.
Guido Verhoeven - One of the best experts on this subject based on the ideXlab platform.
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identification of the phosphatidic acid phosphatase type 2a isozyme as an androgen regulated gene in the human prostatic Adenocarcinoma Cell Line lncap
Journal of Biological Chemistry, 1998Co-Authors: William Ulrix, Johannes V Swinnen, Walter Heyns, Guido VerhoevenAbstract:Abstract Differential display was used to identify novel androgen-regulated genes in the human prostatic Adenocarcinoma Cell Line LNCaP. A 322-base pair cDNA fragment that was consistently induced by the synthetic androgen R1881 revealed 100% homology with the human phosphatidic acid phosphatase type 2a isozyme very recently reported by Kai et al. (PAP-2a; Kai., M., Wada, I., Imai, S.-i., Sakane, F., and Kanoh, H. (1997) J. Biol. Chem.272, 24572–24578). The fragment was used to clone the corresponding cDNA from a human prostate library. The deduced amino acid sequence confirmed the identity with human PAP-2a. The inducibility of PAP-2a mRNA by androgens was confirmed by Northern blot hybridization. The effect was time- and dose-dependent with a maximal stimulation (4-fold) after 24 h of treatment with 10−9 m R1881. The steroid specificity of PAP-2a mRNA regulation was found to be in agreement with the aberrant ligand specificity of the mutated androgen receptor in LNCaP Cells, supporting the involvement of the androgen receptor in the induction process. Furthermore, low basal levels of PAP-2a mRNA and absence of androgen inducibility were observed in the poorly differentiated and androgen receptor-negative Cell Lines PC-3 and DU-145. Induction of PAP-2a mRNA was not affected by the protein synthesis inhibitor cycloheximide and was accompanied by a marked increase in PAP-2 activity as measured by the conversion of phosphatidic acid into diacylglycerol in membrane fractions of LNCaP. Comparison of the expression of PAP-2a mRNA in 50 different human tissues revealed ubiquitous expression. The highest levels, however, were observed in the prostate. Since PAP-2 plays a pivotal role in the control of signal transduction by lipid mediators such as phosphatidate, lysophosphatidate, and ceramide-1-phosphate, the ability of androgens to stimulate the expression and activity of this enzyme in prostatic Cells may provide an important opportunity for cross-talk between signaling pathways involving lipid mediators and androgens.
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a human gene encoding diazepam binding inhibitor acy1 coa binding protein transcription and hormonal regulation in the androgen sensitive human prostatic Adenocarcinoma Cell Line lncap
DNA and Cell Biology, 1996Co-Authors: Johannes V Swinnen, Murielle Esquenet, Joelle Rosseels, Frank Claessens, Wilfried Rombauts, Walter Heyns, Guido VerhoevenAbstract:ABSTRACT Diazepam-binding inhibitor (DBI)/acyl-CoA-binding protein (ACBP) is a highly conserved 10-kD polypeptide expressed in various organs and implicated in the regulation of multiple biological processes such as GABAA/benzodiazepine receptor modulation, acyl-CoA metabolism, steroidogenesis, and insulin secretion. To extend our knowledge about the biology of DBI/ACBP and to elucidate the molecular mechanisms responsible for regulating DBI/ACBP gene expression, we have studied the androgen-regulated expression of DBI/ACBP transcripts in the human prostatic Adenocarcinoma Cell Line LNCaP and have cloned and characterized a human gene encoding DBI/ACBP. Northern blotting, reverse transcription-assisted polymerase chain reaction (RT-PCR), ribonuclease protection, and 5′ RACE analysis (rapid amplification of cDNA ends) of DBI/ACBP transcripts in LNCaP Cells revealed androgen-regulated expression of multiple transcripts originating from multiple transcription start sites and alternative processing. The most ...
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a human gene encoding diazepam binding inhibitor acyl coa binding protein transcription and hormonal regulation in the androgen sensitive human prostatic Adenocarcinoma Cell Line lncap
DNA and Cell Biology, 1996Co-Authors: Johannes V Swinnen, Murielle Esquenet, Joelle Rosseels, Frank Claessens, Wilfried Rombauts, Walter Heyns, Guido VerhoevenAbstract:ABSTRACT Diazepam-binding inhibitor (DBI)/acyl-CoA-binding protein (ACBP) is a highly conserved 10-kD polypeptide expressed in various organs and implicated in the regulation of multiple biological processes such as GABAA/benzodiazepine receptor modulation, acyl-CoA metabolism, steroidogenesis, and insulin secretion. To extend our knowledge about the biology of DBI/ACBP and to elucidate the molecular mechanisms responsible for regulating DBI/ACBP gene expression, we have studied the androgen-regulated expression of DBI/ACBP transcripts in the human prostatic Adenocarcinoma Cell Line LNCaP and have cloned and characterized a human gene encoding DBI/ACBP. Northern blotting, reverse transcription-assisted polymerase chain reaction (RT-PCR), ribonuclease protection, and 5′ RACE analysis (rapid amplification of cDNA ends) of DBI/ACBP transcripts in LNCaP Cells revealed androgen-regulated expression of multiple transcripts originating from multiple transcription start sites and alternative processing. The most ...
Bruce A Lessey - One of the best experts on this subject based on the ideXlab platform.
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characterization of integrin expression in a well differentiated endometrial Adenocarcinoma Cell Line ishikawa
The Journal of Clinical Endocrinology and Metabolism, 1997Co-Authors: Arthur J Castelbaum, Abiodun O Ilesanmi, Steven G Somkuti, Lei Ying, Jinghai Sun, Bruce A LesseyAbstract:The pattern of constitutive and cycle-dependent integrins in normal endometrium has recently been established, suggesting a role for Cell adhesion molecules in endometrial receptivity and implantation. Currently few, if any, models exist for the study of human endometrial integrins and their role in establishment of the receptive endometrial phenotype. The Ishikawa Cell Line maintains functional estrogen receptors and progesterone receptors. The progesterone receptors in these Cells are inducible by priming with estradiol and down-regulated by treatment with progesterone. In the present study the pattern of integrin expression in this well differentiated endometrial Cell Line is compared to that in normal endometrial epithelium using immunohistochemistry and flow cytometry and is confirmed by immunoprecipitation, Western immunoblot, and PCR. Like normal endometrial epithelium, Ishikawa Cells maintain constitutive expression of alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 4. PCR demonstrates the expected size fragments of each, although evidence for alternatively spliced forms of the alpha 2-subunit was noted. Progesterone treatment of estradiol-primed Cells resulted in increased expression of the alpha 1 beta 1 collagen-laminin receptor and suppression of the alpha v beta 3 vitronectin receptor, two of the cycle-dependent integrins expressed by normal endometrial epithelium. These data support the use of Ishikawa Cells as an exCellent model to study the regulation endometrial integrins and advance our understanding of hormonally mediated events surrounding implantation.
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characterization of the functional progesterone receptor in an endometrial Adenocarcinoma Cell Line ishikawa progesterone induced expression of the α1 integrin
The Journal of Steroid Biochemistry and Molecular Biology, 1996Co-Authors: Bruce A Lessey, Abiodun O Ilesanmi, Arthur J Castelbaum, Lingwen Yuan, Steven G Somkuti, P G Satyaswaroop, Kristof ChwaliszAbstract:Abstract Endometrial progesterone receptors (PR) are regulated by both estrogen (E2) and progesterone (P) and mediate the expression of specific endometrial proteins. Ishikawa Cells are a well-differentiated human endometrial Adenocarcinoma Cell Line, with both estrogen receptors (ER) and PR, regulated in a manner similar to that of normal endometrium. Immunohistochemical and biochemical analyses demonstrate that the concentration of PR is increased by E2 priming and decreased by subsequent treatment with P. Scatchard plot analysis showed a Kd of 1 nM. On the basis of biochemical analysis, PR concentrations reached approximately 1400 fmol/mg cytosol protein in Cells after treatment with E2 (10−8 M) for 4 days. Immunoprecipitation and Western blot studies revealed the presence of both the 116 kDa and 81 kDa proteins with multiple isoforms of the high molecular weight (MW) protein. Northern blot analysis demonstrated transcriptional control of PR by steroid treatment. These studies demonstrate the coordinate regulation of all PR mRNA species. The functionality of Ishikawa PR was demonstrated by the expression of α1β1 integrin in response to E2 plus P, at the level of transcription and translation. This effect was blocked by the addition of the anti-progestin, RU-486. These studies reconfirm that the Ishikawa Cell Line is an exCellent model for the study of hormonally regulated events in the human endometrial epithelium.
Arthur J Sytkowski - One of the best experts on this subject based on the ideXlab platform.
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differentially expressed genes associated with cisplatin resistance in human ovarian Adenocarcinoma Cell Line a2780
Cancer Letters, 2011Co-Authors: Peter Solar, Arthur J SytkowskiAbstract:Ovarian cancer Cells are usually initially sensitive to platinum-based chemotherapy, such as cisplatin (CDDP), but typically become resistant over time. Such drug resistance is a serious impediment to successful disease treatment, and the molecular mechanisms responsible for resistance are not fully understood. In search of novel mechanisms that may lead to the development of CDDP chemoresistance, we used subtractive hybridization to identify differentially expressed genes in CDDP resistant CP70 and C200 Cells vs. CDDP sensitive A2780 human ovarian Adenocarcinoma Cells. We analyzed 256 randomly selected clones. Subtraction efficiency was determined by dot blot and DNA sequencing. Confirmation of differentially expressed cDNAs was done by virtual northern blot analysis, and 17 genes that were differentially expressed in CDDP resistant Cell Lines vs. CDDP sensitive A2780 Cells were identified. The expression of 10 of these genes was low or undetectable in sensitive A2780 Cells in comparison to resistant Cells and an additional seven genes were more highly expressed in resistant CP70 and C200 vs. A2780 Cells. Our identified genes are involved in numerous and diverse Cellular processes, such as inhibition of apoptosis (ARHGDIB), stress response (HSPCA, TRA1), chromatin condensation (CNAP1, RanBP2), invasiveness of Cells (MMP10), alteration of Ca(2+) homeostasis (ASPH, ATP2B1) and others. Further characterization of these genes and gene products should yield important insights into the biology of CDDP resistance in ovarian carcinoma.
David Eisel - One of the best experts on this subject based on the ideXlab platform.
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radiation induced alterations in immunogenicity of a murine pancreatic ductal Adenocarcinoma Cell Line
Scientific Reports, 2020Co-Authors: Philipp Schroter, Laura Hartmann, Wolfram Osen, Daniel Baumann, Rienk Offringa, David EiselAbstract:Pancreatic ductal Adenocarcinoma (PDA) is highlighted by resistance to radiotherapy with the possible exception of hypofractionated irradiation. As single photon doses were reported to increase immunogenicity, we investigated dose-dependent irradiation effects on clonogenic survival, expression of immunologically relevant Cell surface molecules and susceptibility to cytotoxic T Cell (CTL) mediated killing using a murine PDA Cell Line. Clonogenicity decreased in a dose-responsive manner showing enhanced radioresistance at single photon doses below 5 Gy. Cell cycle analysis revealed a predominant G2/M arrest, being most pronounced 12 h after irradiation. Polyploidy increased in a dose- and time-dependent manner reaching a maximum frequency 60 h following irradiation with 10 Gy. Irradiation increased surface expression of MHC class I molecules and of immunological checkpoint molecules PDL-1 and CD73, especially at doses ≥ 5 Gy, but not of MHC class II molecules and CXCR4 receptors. Cytotoxicity assays revealed increased CTL lysis of PDA Cells at doses ≥ 5 Gy. For the PDA Cell Line investigated, our data show for the first time that single photon doses ≥ 5 Gy effectively inhibit colony formation and induce a G2/M Cell cycle arrest. Furthermore, expression levels of immunomodulatory Cell surface molecules became altered possibly enhancing the susceptibility of tumour Cells to CTL lysis.