Visit our Expo - Redox and Inflammation signaling 2012

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Session X : Cell death in cancer Poster X, 63 DMNQ S64 induces apoptosis via caspase activation and cyclooxygenase-2 inhibition in human non-small cell A549 lung cancer cells Eu-Soo Lim, Yun-Hee Rhee, Eun-Ok Lee, Eun-Young Lee, Sung-Hoon Kim Department of Oncology, Graduate School of East-West Medical Science, KyungHee University, Yongin 449-701, Republic of Korea. E-mail:sungkim7@khu.ac.kr Shikonin has been shown to induce apoptosis and inhibit angiogenesis in vivo and in vitro. However, it still has drawbacks of solubility and toxicity. Thus, in the present study, the underlying apoptotic mechanism of 6-ppim (1-propoxyiminoalkyl)-DMNQ-S64 (DMNQ S64), a shikonin derivative, was examined. DMNQ S64 exerted cytotoxicity against human A549 lung carcinoma cells with IC50 of 30 µM. Apoptotic bodies were observed in DMNQ S64 treated A549 cells. DMNQ S64 also increased sub G1 DNA peaks in a concentration dependent manner by flow cytometric analysis. Western blotting has revealed that DMNQ S64 effectively activates the expression of caspase 8, 9 and 3, cleaves poly(ADP-ribose) polymerase and increases the ratio of Bax/Bcl-2. Furthermore, mitochondrial membrane potential was reduced in a concentration dependent manner by DMNQ S64. It significantly inhibited the level of prostaglandin E2 by enzyme linked immunosorbent assay and downregulated the expression of cyclooxygenase-2 (COX-2) in a concentration dependent manner by Western blotting. Taken together, DMNQ S64 may exhibit cytotoxicity against A549 cells via caspase activation and COX-2 inhibition. - 396 -
Session X : Cell death in cancer Poster X, 64 The effect on cell death in drug and CD95-mediated apoptosis by the apoptosis enhancer Daxx in renal cell carcinoma C Mahotka, N Wethkamp, P Reinecke, and HE Gabbert Institute of Pathology, Heinrich Heine-University, Duesseldorf, Germany; e-mail: mahotka@med.uni-duesseldorf.de Introduction: Deregulation of apoptosis is involved in the development of cancer. Expression of Daxx is implicated in apoptosis but whether its function is pro- or anti-apoptotic is still discussed controversial. Daxx is involved in the regulation of p53 dependent transcription and associates with the promyelocytic leukemia protein (PML) in speckled subnuclear structures so called PML oncogenic domains (PODs). Overexpression-based experiments in renal cell carcinoma (RCC) were used to explore the impact of Daxx on the CD95-dependent apoptosis and cell death induced by different anticancer agents such as Etoposide, Topotecan, Taxol and Doxorubicine. Results: 1. Constitutive overexpression of Daxx in the CD95-ligand sensitive human RCC cell line clearCa-6 (clear-Ca-6/GFP-Daxx) has no influence on cell growth. 2. Treatment of clearCa-6/GFP-Daxx with the CD95-receptor agonistic antibody CH11 leads to no further enhancement of the CD95-dependent apoptosis compared to control cell line clear- Ca-6/GFP as analyzed by MTT Assay and Caspase-8 and PARP Western Blot, respectively. 3. Daxx overexpression in the CD95-ligand resistent RCC cell line clearCa-2 (clearCa-2/GFP- Daxx) also causes no sensitization to the CD95-dependent apoptosis. 4. Although Daxx is known to trigger CD95-mediated apoptosis via the activation of JNK by a Caspase-8 independent mechanism, even under Caspase-8 inhibition no Daxx-mediated modulation of the CD95-mediated apoptosis was detectable and moreover, no differences in CD95-mediated JNK aktivation were obvious as shown by in vitro kinase assays. 5. Treatment of both GFP- Daxx transduced cell lines with various anticancer drugs points to a protective role of Daxx during Taxol-dependent apoptosis of clearCa-2/GFP-Daxx, which is probably mediated by an enhanced activation of the p38/JNK pathway as shown by in vitro kinase assays. Conclusions: Our study suggests that the CD95-mediated apoptosis in renal cell carcinoma is not effected by the overexpression of the apoptosis enhancer Daxx. In contrast, the data indicate a rather anti-apoptotic than pro-apoptotic role for Daxx in human RCC as shown by the Daxx overexpression-mediated protective effect during Taxol-dependent apoptosis in the RCC cell line clearCa-2. - 397 -
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- 1 - Luxembourg, January 25th to 2
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Table of content PREFACE ..........
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Preface In 1998, we organized the f
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Acknowledgments This meeting has be
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Group B (15h00 - 17h00) Session V.
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- 11 - Exhibition
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Visit our Expo (in alphabetical ord
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Thursday January 26th, 2006 (Early
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Thursday January 26th, 2006 (Evenin
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Regulation of inflammation and gluc
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Saturday January 28th, 2006 (Early
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Oral presentations (by alphabetical
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4: : Lottin S, Vercoutter-Edouart A
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the B-Raf/mitogen-activated/extrace
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Albertini MC, Accorsi A, Citterio B
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AP-1-dependent gene expression in s
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Jaks and cytokine receptors - an in
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The Role of Met-Gab1 Signalling in
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The mammalian tumor suppressor Scri
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SIGNAL TRANSDUCTION BY STRESS-ACTIV
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Title to be announced Caroline Dive
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Mechanisms of DNA methylation in ma
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Blocking the "4 Integrin-Paxillin I
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Regulation of NF-kB-dependent trans
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The immunomodulator AS101 induces g
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Signaling pathways leading to the a
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Boute, N., Jockers, R. and Issad, T
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Jespsen JS, Sorensen MD and Wengel
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8. Nishikawa, H., Kawai, K., Tanaka
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9) Proteome analysis of rat pancrea
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MicroRNA is an anti-apoptotic facto
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Resveratrol inhibits phorbol ester-
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Cross-talk between angiotensin II a
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Multiple role of histamine H 1 rece
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PI3K Targeting by the Beta-GBP Cyto
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D.P. Chopra, R.E. Menard, J. Janusz
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[2] Meijer, L., Flajolet, M. and Gr
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[4] Niemand, C., Nimmesgern, A., Ha
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Oncogenic signaling by mutant p53 M
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activity of the Peroxisome Prolifer
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Restauration of SHIP-1 activity in
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Hypoxia Signaling. Impact on Tumor
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5. Sokolov EI, Zykov KA, Pukhalsky
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HOW ANTITOXIC AND ANTICANCER AGENTS
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Listeria monocytogenes induced Rac1
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Epigenetic Regulation of Stem Cell
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Survey on in vitro cell death induc
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Distinct roles of IRF-3 and IRF-7 i
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Redox-Sensitive Transcription Facto
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Epigenic control of MHC2TA transcri
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Attenuation of MSK1-driven NF-kB ge
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Talking to chromatin: Silencers Sil
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Ubiquitin ligase Smurf1 controls os
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Workshop presentations (by alphabet
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Ambion MicroRNAs (miRNAs) are small
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Organizer: BIOBASE GmbH Date: Janua
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Reliable and efficient gene Knock-d
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Exploring ubiquitin signaling with
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Poster presentations Poster are cla
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Session I : protein domains Poster
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Session II. Receptor signaling and
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Session II : Receptor signaling and
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Session III. Protein kinase cascade
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Session III : Protein kinase cascad
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Session IV. Protein kinase inhibito
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IV. Protein kinase inhibitors: insi
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IV. Protein kinase inhibitors: insi
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V. Phosphatases as key cell signali
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VI. Proteasome degradation pathways
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VI. Proteasome degradation pathways
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Session VII. Stem cell specific cel
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VIII. Inflammation specific signali
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Session IX. Novel compounds targeti
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Session X : Cell death in cancer -
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Session X : Cell death in cancer Po
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Session XI: Cell death and cardiova
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Session XII : Cell death and neurod
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Session XIII : Cell signaling pathw
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Session XIV : Transcriptional and t
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Session XV : Reactive oxygen specie
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Session XVI : Chemopreventive agent
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Session XVII : Cell signaling in he
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Dr. Nassera Aouali L-1526 Luxembour
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Dr. Giordano Bianchi Clinic of inte
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Mrs. Isabel Burghardt Laboratory of
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Pr. Czeslaw Cierniewski 92-215 Lodz
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Mr. Igotz Delgado Biochemistry 4894
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Mrs. Anissa Fergani INSERM U-692 67
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Dr. Mark Ginsberg Mail code 0726 92
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Dr. Jochen Hefl Division of Signal
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Mr. Jan Jepsen 2100 Copenhagen DNK
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Pr. Young Min Kim Division of Biolo
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Mr. Christoph Lahtz AG Tumorgenetik
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Pr. Etta Livneh 84105 Beer Sheva IS
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Mrs. Rasa Merzvinskyte Department o
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Mr. Gustav Nilsonne Department of L
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Mrs. Christel Péqueux Tumour and D
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Dr. Gabriella Regis Tumor Immunolog
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Dr. Carsten Scheller 97078 Wuerzbur
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Mr. Yoo-Cheol Song Laboratory of Gy
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Mrs. Jessica Wagener 40225 Duesseld
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Pr. Moncef ZOUALI Centre Viggo Pete
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