Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
An Inducible Pathway for Degradation of FLIP Protein Sensitizes
Tumor Cells to TRAIL-induced Apoptosis*
Youngsoo
Kim,
Nanjoo
Suh,
Michael
Sporn, and
John C.
Reed§
From The Burnham Institute, La Jolla, California 92037 and the
Department of Pharmacology, Dartmouth Medical School,
Hanover, New Hampshire 03755
TRAIL (Apo2 ligand) is a member of the tumor
necrosis factor (TNF) family of cytokines that induces apoptosis.
Because TRAILpreferentially kills tumor cells, sparing normal tissues,
interesthas emerged in applying this biological factor for cancer
therapyin humans. However, not all tumors respond to TRAIL, raising
questionsabout resistance mechanisms. We demonstrate here that a
varietyof natural and synthetic ligands of peroxisome
proliferator-activatedreceptor- (PPAR) sensitize tumor but not
normal cells to apoptosisinduction by TRAIL. PPAR ligands
selectively reduce levels ofFLIP, an apoptosis-suppressing protein
that blocks early eventsin TRAIL/TNF family death receptor signaling.
Both PPAR agonistsand antagonists displayed these effects,
regardless of the levelsof PPAR expression and even in the presence
of a PPAR dominant-negativemutant, indicating a PPAR-independent
mechanism. Reductions inFLIP and sensitization to TRAIL-induced
apoptosis were also notcorrelated with NF-B, further suggesting a
novel mechanism. PPARmodulators induced ubiquitination and
proteasome-dependent degradationof FLIP, without
concomitant reductions in FLIP mRNA. The findingssuggest the
existence of a pharmacologically regulated novel targetof this class
of drugs that controls FLIP protein turnover, andraise the possibility
of combining PPAR modulators with TRAILfor more efficacious
elimination of tumor cells throughapoptosis.
Novel Phosphorylation and Ubiquitination Sites Regulate Reactive Oxygen Species-dependent Degradation of Anti-apoptotic c-FLIP Protein.
R. P. Wilkie-Grantham, S.-I. Matsuzawa, and J. C. Reed (2013)
J. Biol. Chem.
288, 12777-12790
|Abstract »|Full Text »|PDF »
mTOR Complex 2 Is Involved in Regulation of Cbl-Dependent c-FLIP Degradation and Sensitivity of TRAIL-Induced Apoptosis.
L. Zhao, P. Yue, F. R. Khuri, and S.-Y. Sun (2013)
Cancer Res.
73, 1946-1957
|Abstract »|Full Text »|PDF »
Activated T Cell Exosomes Promote Tumor Invasion via Fas Signaling Pathway.
Z. Cai, F. Yang, L. Yu, Z. Yu, L. Jiang, Q. Wang, Y. Yang, L. Wang, X. Cao, and J. Wang (2012)
J. Immunol.
188, 5954-5961
|Abstract »|Full Text »|PDF »
The Novel Akt Inhibitor API-1 Induces c-FLIP Degradation and Synergizes with TRAIL to Augment Apoptosis Independent of Akt Inhibition.
B. Li, H. Ren, P. Yue, M. Chen, F. R. Khuri, and S.-Y. Sun (2012)
Cancer Prevention Research
5, 612-620
|Abstract »|Full Text »|PDF »
The NEDD8-Activating Enzyme Inhibitor, MLN4924, Cooperates with TRAIL to Augment Apoptosis through Facilitating c-FLIP Degradation in Head and Neck Cancer Cells.
L. Zhao, P. Yue, S. Lonial, F. R. Khuri, and S.-Y. Sun (2011)
Mol. Cancer Ther.
10, 2415-2425
|Abstract »|Full Text »|PDF »
Celecoxib Promotes c-FLIP Degradation through Akt-Independent Inhibition of GSK3.
S. Chen, W. Cao, P. Yue, C. Hao, F. R. Khuri, and S.-Y. Sun (2011)
Cancer Res.
71, 6270-6281
|Abstract »|Full Text »|PDF »
TNF Is Necessary for Castration-Induced Prostate Regression, Whereas TRAIL and FasL Are Dispensable.
J. S. Davis, K. L. Nastiuk, and J. J. Krolewski (2011)
Mol. Endocrinol.
25, 611-620
|Abstract »|Full Text »|PDF »
Signaling through C/EBP Homologous Protein and Death Receptor 5 and Calpain Activation Differentially Regulate THP-1 Cell Maturation-Dependent Apoptosis Induced by Shiga Toxin Type 1.
M.-S. Lee, R. P. Cherla, E. K. Lentz, D. Leyva-Illades, and V. L. Tesh (2010)
Infect. Immun.
78, 3378-3391
|Abstract »|Full Text »|PDF »
Herpes Simplex Virus Type 1 (HSV-1)-Induced Apoptosis in Human Dendritic Cells as a Result of Downregulation of Cellular FLICE-Inhibitory Protein and Reduced Expression of HSV-1 Antiapoptotic Latency-Associated Transcript Sequences.
A. Kather, M. J. Raftery, G. Devi-Rao, J. Lippmann, T. Giese, R. M. Sandri-Goldin, and G. Schonrich (2010)
J. Virol.
84, 1034-1046
|Abstract »|Full Text »|PDF »
Regulation of Colorectal Cancer Cell Apoptosis by the n-3 Polyunsaturated Fatty Acids Docosahexaenoic and Eicosapentaenoic.
A. Giros, M. Grzybowski, V. R. Sohn, E. Pons, J. Fernandez-Morales, R. M. Xicola, P. Sethi, J. Grzybowski, A. Goel, C. R. Boland, et al. (2009)
Cancer Prevention Research
2, 732-742
|Abstract »|Full Text »|PDF »
Engineering a leucine zipper-TRAIL homotrimer with improved cytotoxicity in tumor cells.
D. V. Rozanov, A. Y. Savinov, V. S. Golubkov, O. L. Rozanova, T. I. Postnova, E. A. Sergienko, S. Vasile, A. E. Aleshin, M. F. Rega, M. Pellecchia, et al. (2009)
Mol. Cancer Ther.
8, 1515-1525
|Abstract »|Full Text »|PDF »
Activation-induced Degradation of FLIPL Is Mediated via the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Macrophages.
B. Shi, T. Tran, R. Sobkoviak, and R. M. Pope (2009)
J. Biol. Chem.
284, 14513-14523
|Abstract »|Full Text »|PDF »
Caspase-mediated Cleavage of {beta}-Catenin Precedes Drug-induced Apoptosis in Resistant Cancer Cells.
S. Senthivinayagam, P. Mishra, S. K. Paramasivam, S. Yallapragada, M. Chatterjee, L. Wong, A. Rana, and B. Rana (2009)
J. Biol. Chem.
284, 13577-13588
|Abstract »|Full Text »|PDF »
Bortezomib Overcomes Tumor Necrosis Factor-related Apoptosis-inducing Ligand Resistance in Hepatocellular Carcinoma Cells in Part through the Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway.
K.-F. Chen, P.-Y. Yeh, C. Hsu, C.-H. Hsu, Y.-S. Lu, H.-P. Hsieh, P.-J. Chen, and A.-L. Cheng (2009)
J. Biol. Chem.
284, 11121-11133
|Abstract »|Full Text »|PDF »
Suppression of cFLIP by Lupeol, a Dietary Triterpene, Is Sufficient to Overcome Resistance to TRAIL-Mediated Apoptosis in Chemoresistant Human Pancreatic Cancer Cells.
I. Murtaza, M. Saleem, V. M. Adhami, B. B. Hafeez, and H. Mukhtar (2009)
Cancer Res.
69, 1156-1165
|Abstract »|Full Text »|PDF »
Transcriptional and post-translational regulation of Flip, an inhibitor of Fas-mediated apoptosis, in human gut inflammation.
F Caprioli, C Stolfi, R Caruso, D Fina, G Sica, L Biancone, F Pallone, and G Monteleone (2008)
Gut
57, 1674-1680
|Abstract »|Full Text »|PDF »
Involvement of c-FLIP and survivin down-regulation in flexible heteroarotinoid-induced apoptosis and enhancement of TRAIL-initiated apoptosis in lung cancer cells.
Y. Lin, X. Liu, P. Yue, D. M. Benbrook, K. D. Berlin, F. R. Khuri, and S.-Y. Sun (2008)
Mol. Cancer Ther.
7, 3556-3565
|Abstract »|Full Text »|PDF »
Glycogen Synthase Kinase 3{beta} Regulates Cell Death Induced by Synthetic Triterpenoids.
R. Vene, P. Larghero, G. Arena, M. B. Sporn, A. Albini, and F. Tosetti (2008)
Cancer Res.
68, 6987-6996
|Abstract »|Full Text »|PDF »
The natural product honokiol preferentially inhibits cellular FLICE-inhibitory protein and augments death receptor-induced apoptosis.
S. M. Raja, S. Chen, P. Yue, T. M. Acker, B. Lefkove, J. L. Arbiser, F. R. Khuri, and S.-Y. Sun (2008)
Mol. Cancer Ther.
7, 2212-2223
|Abstract »|Full Text »|PDF »
Dependence of Reactive Oxygen Species and FLICE Inhibitory Protein on Lipofectamine-Induced Apoptosis in Human Lung Epithelial Cells.
L. Kongkaneramit, N. Sarisuta, N. Azad, Y. Lu, A. K. V. Iyer, L. Wang, and Y. Rojanasakul (2008)
J. Pharmacol. Exp. Ther.
325, 969-977
|Abstract »|Full Text »|PDF »
The Fas Death Signaling Pathway Connecting Reactive Oxygen Species Generation and FLICE Inhibitory Protein Down-Regulation.
L. Wang, N. Azad, L. Kongkaneramit, F. Chen, Y. Lu, B.-H. Jiang, and Y. Rojanasakul (2008)
J. Immunol.
180, 3072-3080
|Abstract »|Full Text »|PDF »
CCAAT/Enhancer Binding Protein Homologous Protein-Dependent Death Receptor 5 Induction and Ubiquitin/Proteasome-Mediated Cellular FLICE-Inhibitory Protein Down-Regulation Contribute to Enhancement of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis by Dimethyl-Celecoxib in Human Non Small-Cell Lung Cancer Cells.
S. Chen, X. Liu, P. Yue, A. H. Schonthal, F. R. Khuri, and S.-Y. Sun (2007)
Mol. Pharmacol.
72, 1269-1279
|Abstract »|Full Text »|PDF »
The Multikinase Inhibitor Sorafenib Potentiates TRAIL Lethality in Human Leukemia Cells in Association with Mcl-1 and cFLIPL Down-regulation.
R. R. Rosato, J. A. Almenara, S. Coe, and S. Grant (2007)
Cancer Res.
67, 9490-9500
|Abstract »|Full Text »|PDF »
Bortezomib Sensitizes Non-Hodgkin's Lymphoma Cells to Apoptosis Induced by Antibodies to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptors TRAIL-R1 and TRAIL-R2.
M. R. Smith, F. Jin, and I. Joshi (2007)
Clin. Cancer Res.
13, 5528s-5534s
|Abstract »|Full Text »|PDF »
A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B), sensitizes leukemia cells to apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL) through 15-deoxy-{Delta}12, 14 prostaglandin J2 production.
H. Hasegawa, Y. Yamada, K. Komiyama, M. Hayashi, M. Ishibashi, T. Sunazuka, T. Izuhara, K. Sugahara, K. Tsuruda, M. Masuda, et al. (2007)
Blood
110, 1664-1674
|Abstract »|Full Text »|PDF »
Transcriptional network governing the angiogenic switch in human pancreatic cancer.
A. Abdollahi, C. Schwager, J. Kleeff, I. Esposito, S. Domhan, P. Peschke, K. Hauser, P. Hahnfeldt, L. Hlatky, J. Debus, et al. (2007)
PNAS
104, 12890-12895
|Abstract »|Full Text »|PDF »
Effects of Thiazolidinediones on Differentiation, Proliferation, and Apoptosis.
F.-S. Chou, P.-S. Wang, S. Kulp, and J. J. Pinzone (2007)
Mol. Cancer Res.
5, 523-530
|Abstract »|Full Text »|PDF »
Critical Role for Fas-Associated Death Domain-Like Interleukin-1-Converting Enzyme-Like Inhibitory Protein in Anoikis Resistance and Distant Tumor Formation.
I. A. Mawji, C. D. Simpson, R. Hurren, M. Gronda, M. A. Williams, J. Filmus, J. Jonkman, R. S. Da Costa, B. C. Wilson, M. P. Thomas, et al. (2007)
J Natl Cancer Inst
99, 811-822
|Abstract »|Full Text »|PDF »
The Farnesyltransferase Inhibitor R115777 Up-regulates the Expression of Death Receptor 5 and Enhances TRAIL-Induced Apoptosis in Human Lung Cancer Cells.
Y. Qiu, X. Liu, W. Zou, P. Yue, S. Lonial, F. R. Khuri, and S.-Y. Sun (2007)
Cancer Res.
67, 4973-4980
|Abstract »|Full Text »|PDF »
The Proteasome Inhibitor PS-341 (Bortezomib) Up-Regulates DR5 Expression Leading to Induction of Apoptosis and Enhancement of TRAIL-Induced Apoptosis Despite Up-Regulation of c-FLIP and Survivin Expression in Human NSCLC Cells.
X. Liu, P. Yue, S. Chen, L. Hu, S. Lonial, F. R. Khuri, and S.-Y. Sun (2007)
Cancer Res.
67, 4981-4988
|Abstract »|Full Text »|PDF »
Cellular FLICE-inhibitory protein regulates chemotherapy-induced apoptosis in breast cancer cells.
K. M.A. Rogers, M. Thomas, L. Galligan, T. R. Wilson, W. L. Allen, H. Sakai, P. G. Johnston, and D. B. Longley (2007)
Mol. Cancer Ther.
6, 1544-1551
|Abstract »|Full Text »|PDF »
Selective Down-Regulation of Glioma-Associated Oncogene 2 Inhibits the Proliferation of Hepatocellular Carcinoma Cells.
Y. Kim, J. W. Yoon, X. Xiao, N. M. Dean, B. P. Monia, and E. G. Marcusson (2007)
Cancer Res.
67, 3583-3593
|Abstract »|Full Text »|PDF »
Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort.
A. Meinander, T. S. Soderstrom, A. Kaunisto, M. Poukkula, L. Sistonen, and J. E. Eriksson (2007)
J. Immunol.
178, 3944-3953
|Abstract »|Full Text »|PDF »
Selective Inhibition of I{kappa}B Kinase Sensitizes Mantle Cell Lymphoma B Cells to TRAIL by Decreasing Cellular FLIP Level.
G. Roue, P. Perez-Galan, M. Lopez-Guerra, N. Villamor, E. Campo, and D. Colomer (2007)
J. Immunol.
178, 1923-1930
|Abstract »|Full Text »|PDF »
Cellular FLICE-Inhibitory Protein Down-regulation Contributes to Celecoxib-Induced Apoptosis in Human Lung Cancer Cells.
X. Liu, P. Yue, A. H. Schonthal, F. R. Khuri, and S.-Y. Sun (2006)
Cancer Res.
66, 11115-11119
|Abstract »|Full Text »|PDF »
Flavopiridol Induces Cellular FLICE-Inhibitory Protein Degradation by the Proteasome and Promotes TRAIL-Induced Early Signaling and Apoptosis in Breast Tumor Cells..
C. Palacios, R. Yerbes, and A. Lopez-Rivas (2006)
Cancer Res.
66, 8858-8869
|Abstract »|Full Text »|PDF »
Inorganic selenium sensitizes prostate cancer cells to TRAIL-induced apoptosis through superoxide/p53/Bax-mediated activation of mitochondrial pathway..
H. Hu, C. Jiang, T. Schuster, G.-X. Li, P. T. Daniel, and J. Lu (2006)
Mol. Cancer Ther.
5, 1873-1882
|Abstract »|Full Text »|PDF »
Transduction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand into Hematopoietic Cells Leads to Inhibition of Syngeneic Tumor Growth In vivo..
K. Song, N. Benhaga, R. L. Anderson, and R. Khosravi-Far (2006)
Cancer Res.
66, 6304-6311
|Abstract »|Full Text »|PDF »
Beyond peroxisome proliferator-activated receptor {gamma} signaling: the multi-facets of the antitumor effect of thiazolidinediones..
J-R Weng, C-Y Chen, J J Pinzone, M D Ringel, and C-S Chen (2006)
Endocr. Relat. Cancer
13, 401-413
|Abstract »|Full Text »|PDF »
Chemotherapeutic approaches for targeting cell death pathways..
A Peroxisome Proliferator-activated Receptor-{gamma} Agonist, Troglitazone, Facilitates Caspase-8 and -9 Activities by Increasing the Enzymatic Activity of Protein-tyrosine Phosphatase-1B on Human Glioma Cells.
Y. Akasaki, G. Liu, H. H. Matundan, H. Ng, X. Yuan, Z. Zeng, K. L. Black, and J. S. Yu (2006)
J. Biol. Chem.
281, 6165-6174
|Abstract »|Full Text »|PDF »
Identification of Small Molecules that Sensitize Resistant Tumor Cells to Tumor Necrosis Factor-Family Death Receptors.
A. D. Schimmer, M. P. Thomas, R. Hurren, M. Gronda, M. Pellecchia, G. R. Pond, M. Konopleva, D. Gurfinkel, I. A. Mawji, E. Brown, et al. (2006)
Cancer Res.
66, 2367-2375
|Abstract »|Full Text »|PDF »
Nitric Oxide Negatively Regulates Fas CD95-induced Apoptosis through Inhibition of Ubiquitin-Proteasome-mediated Degradation of FLICE Inhibitory Protein.
P. Chanvorachote, U. Nimmannit, L. Wang, C. Stehlik, B. Lu, N. Azad, and Y. Rojanasakul (2005)
J. Biol. Chem.
280, 42044-42050
|Abstract »|Full Text »|PDF »
Down-regulation of c-FLIP contributes to the sensitization effect of 3,3'-diindolylmethane on TRAIL-induced apoptosis in cancer cells.
Cardiomyocyte-Specific Knockout and Agonist of Peroxisome Proliferator-Activated Receptor-{gamma} Both Induce Cardiac Hypertrophy in Mice.
S. Z. Duan, C. Y. Ivashchenko, M. W. Russell, D. S. Milstone, and R. M. Mortensen (2005)
Circ. Res.
97, 372-379
|Abstract »|Full Text »|PDF »
Reactive Oxygen Species Regulate Caspase Activation in Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Resistant Human Colon Carcinoma Cell Lines.
K. Izeradjene, L. Douglas, D. M. Tillman, A. B. Delaney, and J. A. Houghton (2005)
Cancer Res.
65, 7436-7445
|Abstract »|Full Text »|PDF »
Death Receptor-Induced Signaling Pathways Are Differentially Regulated by Gamma Interferon Upstream of Caspase 8 Processing.
D. Siegmund, A. Wicovsky, I. Schmitz, K. Schulze-Osthoff, S. Kreuz, M. Leverkus, O. Dittrich-Breiholz, M. Kracht, and H. Wajant (2005)
Mol. Cell. Biol.
25, 6363-6379
|Abstract »|Full Text »|PDF »
Rapid Turnover of c-FLIPshort Is Determined by Its Unique C-terminal Tail.
M. Poukkula, A. Kaunisto, V. Hietakangas, K. Denessiouk, T. Katajamaki, M. S. Johnson, L. Sistonen, and J. E. Eriksson (2005)
J. Biol. Chem.
280, 27345-27355
|Abstract »|Full Text »|PDF »
Apoptosis-based therapies for hematologic malignancies.
Synthetic Triterpenoids Cooperate with Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand to Induce Apoptosis of Breast Cancer Cells.
M. L. Hyer, R. Croxton, M. Krajewska, S. Krajewski, C. L. Kress, M. Lu, N. Suh, M. B. Sporn, V. L. Cryns, J. M. Zapata, et al. (2005)
Cancer Res.
65, 4799-4808
|Abstract »|Full Text »|PDF »
Selective Knockdown of the Long Variant of Cellular FLICE Inhibitory Protein Augments Death Receptor-mediated Caspase-8 Activation and Apoptosis.
D. A. Sharp, D. A. Lawrence, and A. Ashkenazi (2005)
J. Biol. Chem.
280, 19401-19409
|Abstract »|Full Text »|PDF »
Peroxisome Proliferator-activated Receptor {gamma} Agonists Promote TRAIL-induced Apoptosis by Reducing Survivin Levels via Cyclin D3 Repression and Cell Cycle Arrest.
M. Lu, T. Kwan, C. Yu, F. Chen, B. Freedman, J. M. Schafer, E.-J. Lee, J. L. Jameson, V. C. Jordan, and V. L. Cryns (2005)
J. Biol. Chem.
280, 6742-6751
|Abstract »|Full Text »|PDF »
cFLIPL Inhibits Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated NF-{kappa}B Activation at the Death-inducing Signaling Complex in Human Keratinocytes.
T. Wachter, M. Sprick, D. Hausmann, A. Kerstan, K. McPherson, G. Stassi, E.-B. Brocker, H. Walczak, and M. Leverkus (2004)
J. Biol. Chem.
279, 52824-52834
|Abstract »|Full Text »|PDF »
Sensitization of Cells to TRAIL-induced Apoptosis by Decoy Receptor 3.
Y.-Y. Wu, Y.-C. Chang, T.-L. Hsu, S.-L. Hsieh, and M.-Z. Lai (2004)
J. Biol. Chem.
279, 44211-44218
|Abstract »|Full Text »|PDF »
c-Jun NH2-Terminal Kinase-Mediated Up-regulation of Death Receptor 5 Contributes to Induction of Apoptosis by the Novel Synthetic Triterpenoid Methyl-2-Cyano-3,12-Dioxooleana-1, 9-Dien-28-Oate in Human Lung Cancer Cells.
W. Zou, X. Liu, P. Yue, Z. Zhou, M. B. Sporn, R. Lotan, F. R. Khuri, and S.-Y. Sun (2004)
Cancer Res.
64, 7570-7578
|Abstract »|Full Text »|PDF »
Cellular FLIP Inhibits {beta}-Catenin Ubiquitylation and Enhances Wnt Signaling.
M. Naito, R. Katayama, T. Ishioka, A. Suga, K. Takubo, M. Nanjo, C. Hashimoto, M. Taira, S. Takada, R. Takada, et al. (2004)
Mol. Cell. Biol.
24, 8418-8427
|Abstract »|Full Text »|PDF »
Persistent c-FLIP(L) Expression Is Necessary and Sufficient to Maintain Resistance to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated Apoptosis in Prostate Cancer.
X. Zhang, T.-G. Jin, H. Yang, W. C. DeWolf, R. Khosravi-Far, and A. F. Olumi (2004)
Cancer Res.
64, 7086-7091
|Abstract »|Full Text »|PDF »
Death Induction by Recombinant Native TRAIL and Its Prevention by a Caspase 9 Inhibitor in Primary Human Esophageal Epithelial Cells.
S.-H. Kim, K. Kim, J. G. Kwagh, D. T. Dicker, M. Herlyn, A. K. Rustgi, Y. Chen, and W. S. El-Deiry (2004)
J. Biol. Chem.
279, 40044-40052
|Abstract »|Full Text »|PDF »
Sphingosine Contributes to Glucocorticoid-Induced Apoptosis of Thymocytes Independently of the Mitochondrial Pathway.
S. Lepine, B. Lakatos, M.-P. Courageot, H. Le Stunff, J.-C. Sulpice, and F. Giraud (2004)
J. Immunol.
173, 3783-3790
|Abstract »|Full Text »|PDF »
Keratins Modulate c-Flip/Extracellular Signal-Regulated Kinase 1 and 2 Antiapoptotic Signaling in Simple Epithelial Cells.
S. Gilbert, A. Loranger, and N. Marceau (2004)
Mol. Cell. Biol.
24, 7072-7081
|Abstract »|Full Text »|PDF »
Mcl-1 Mediates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance in Human Cholangiocarcinoma Cells.
M. Taniai, A. Grambihler, H. Higuchi, N. Werneburg, S. F. Bronk, D. J. Farrugia, S. H. Kaufmann, and G. J. Gores (2004)
Cancer Res.
64, 3517-3524
|Abstract »|Full Text »|PDF »
Flavopiridol Induces p53 via Initial Inhibition of Mdm2 and p21 and, Independently of p53, Sensitizes Apoptosis-Reluctant Cells to Tumor Necrosis Factor.
Cotreatment with Histone Deacetylase Inhibitor LAQ824 Enhances Apo-2L/Tumor Necrosis Factor-Related Apoptosis Inducing Ligand-Induced Death Inducing Signaling Complex Activity and Apoptosis of Human Acute Leukemia Cells.
F. Guo, C. Sigua, J. Tao, P. Bali, P. George, Y. Li, S. Wittmann, L. Moscinski, P. Atadja, and K. Bhalla (2004)
Cancer Res.
64, 2580-2589
|Abstract »|Full Text »|PDF »
Expression of NAG-1, a Transforming Growth Factor-{beta} Superfamily Member, by Troglitazone Requires the Early Growth Response Gene EGR-1.
S. J. Baek, J.-S. Kim, J. B. Nixon, R. P. DiAugustine, and T. E. Eling (2004)
J. Biol. Chem.
279, 6883-6892
|Abstract »|Full Text »|PDF »
Induction of redox imbalance and apoptosis in multiple myeloma cells by the novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid.
T. Ikeda, Y. Nakata, F. Kimura, K. Sato, K. Anderson, K. Motoyoshi, M. Sporn, and D. Kufe (2004)
Mol. Cancer Ther.
3, 39-45
|Abstract »|Full Text »
Interferon-{gamma}-Induced Sensitization of Colon Carcinomas to ZD9331 Targets Caspases, Downstream of Fas, Independent of Mitochondrial Signaling and the Inhibitor of Apoptosis Survivin.
J. Geller, I. Petak, K. S. Szucs, K. Nagy, D. M. Tillman, and J. A. Houghton (2003)
Clin. Cancer Res.
9, 6504-6515
|Abstract »|Full Text »|PDF »
Canstatin Inhibits Akt Activation and Induces Fas-dependent Apoptosis in Endothelial Cells.
The proteasome inhibitor PS-341 sensitizes neoplastic cells to TRAIL-mediated apoptosis by reducing levels of c-FLIP.
T. J. Sayers, A. D. Brooks, C. Y. Koh, W. Ma, N. Seki, A. Raziuddin, B. R. Blazar, X. Zhang, P. J. Elliott, and W. J. Murphy (2003)
Blood
102, 303-310
|Abstract »|Full Text »|PDF »
Effects of Prostaglandin Analogues on Human Ciliary Muscle and Trabecular Meshwork Cells.
X. Zhao, K. E. Pearson, D. A. Stephan, and P. Russell (2003)
Invest. Ophthalmol. Vis. Sci.
44, 1945-1952
|Abstract »|Full Text »|PDF »
A Peroxisome Proliferator-activated Receptor-{gamma} Agonist and the p53 Rescue Drug CP-31398 Inhibit the Spontaneous Immortalization of Breast Epithelial Cells.
B.-S. Herbert, V. P. Pearce, L. S. Hynan, D. M. LaRue, W. E. Wright, L. Kopelovich, and J. W. Shay (2003)
Cancer Res.
63, 1914-1919
|Abstract »|Full Text »|PDF »
N. Suh, A. B. Roberts, S. Birkey Reffey, K. Miyazono, S. Itoh, P. t. Dijke, E. H. Heiss, A. E. Place, R. Risingsong, C. R. Williams, et al. (2003)
Cancer Res.
63, 1371-1376
|Abstract »|Full Text »|PDF »
Erythroid Differentiation Sensitizes K562 Leukemia Cells to TRAIL-Induced Apoptosis by Downregulation of c-FLIP.
V. Hietakangas, M. Poukkula, K. M. Heiskanen, J. T. Karvinen, L. Sistonen, and J. E. Eriksson (2003)
Mol. Cell. Biol.
23, 1278-1291
|Abstract »|Full Text »|PDF »
Pediatric Acute Lymphoblastic Leukemia.
W. L. Carroll, D. Bhojwani, D.-J. Min, E. Raetz, M. Relling, S. Davies, J. R. Downing, C. L. Willman, and J. C. Reed (2003)
Hematology
2003, 102-131
|Abstract »|Full Text »|PDF »
The Long Form of FLIP Is an Activator of Caspase-8 at the Fas Death-inducing Signaling Complex.
O. Micheau, M. Thome, P. Schneider, N. Holler, J. Tschopp, D. W. Nicholson, C. Briand, and M. G. Grutter (2002)
J. Biol. Chem.
277, 45162-45171
|Abstract »|Full Text »|PDF »
Shiga-like Toxin Inhibition of FLICE-like Inhibitory Protein Expression Sensitizes Endothelial Cells to Bacterial Lipopolysaccharide-induced Apoptosis.
R. D. Erwert, R. K. Winn, J. M. Harlan, and D. D. Bannerman (2002)
J. Biol. Chem.
277, 40567-40574
|Abstract »|Full Text »|PDF »
TRAIL-induced apoptosis of authentic myeloma cells does not correlate with the procaspase-8/cFLIP ratio.
A. Spencer, S.-L. Yeh, K. Koutrevelis, C. Baulch-Brown ;, N. Mitsiades, C. Mitsiades, K. C. Anderson, and S. P. Treon (2002)
Blood
100, 3049-3050
|Full Text »|PDF »
The triterpenoid CDDO induces apoptosis in refractory CLL B cells.
I. M. Pedersen, S. Kitada, A. Schimmer, Y. Kim, J. M. Zapata, L. Charboneau, L. Rassenti, M. Andreeff, F. Bennett, M. B. Sporn, et al. (2002)
Blood
100, 2965-2972
|Abstract »|Full Text »|PDF »
,
(PPAR
B, further suggesting a
novel mechanism. PPAR
