|
|
 Previous Article | Table of Contents | Next Article 
Cross-Resistance of CD95- and Drug-Induced Apoptosis as a Consequence of Deficient Activation of Caspases (ICE/Ced-3 Proteases)
Marek Los,
Ingrid Herr,
Claudia Friesen,
Simone Fulda,
Klaus Schulze-Osthoff, and
Klaus-Michael Debatin
From Hematology/Oncology, University Children's Hospital, and the Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany; and the Institute of Biochemistry, University of Freiburg, Freiburg, Germany.
The cytotoxic effect of anticancer drugs has been shown to involve induction of apoptosis. We report here that tumor cells resistant to CD95 (APO-1/Fas) -mediated apoptosis were cross-resistant to apoptosis-induced by anticancer drugs. Apoptosis induced in tumor cells by cytarabine, doxorubicin, and methotrexate required the activation of ICE/Ced-3 proteases (caspases), similarly to the CD95 system. After drug treatment, a strong increase of caspase activity was found that preceded cell death. Drug-induced activation of caspases was also found in ex vivo-derived T-cell leukemia cells. Resistance to cell death was conferred by a peptide caspase inhibitor and CrmA, a poxvirus-derived serpin. The peptide inhibitor was effective even if added several hours after drug treatment, indicating a direct involvement of caspases in the execution and not in the trigger phase of drug action. Drug-induced apoptosis was also strongly inhibited by antisense approaches targeting caspase-1 and -3, indicating that several members of this protease family were involved. CD95-resistant cell lines that failed to activate caspases upon CD95 triggering were cross-resistant to drug-mediated apoptosis. Our data strongly support the concept that sensitivity for drug-induced cell death depends on intact apoptosis pathways leading to activation of caspases. The identification of defects in caspase activation may provide molecular targets to overcome drug resistance in tumor cells.
Blood, Vol. 90 No. 8 (July 15), 1997:
pp. 3118-3129
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S Ghavami, M Hashemi, S R Ande, B Yeganeh, W Xiao, M Eshraghi, C J Bus, K Kadkhoda, E Wiechec, A J Halayko, et al.
Apoptosis and cancer: mutations within caspase genes
J. Med. Genet.,
August 1, 2009;
46(8):
497 - 510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Friesen, M. Roscher, A. Alt, and E. Miltner
Methadone, Commonly Used as Maintenance Medication for Outpatient Treatment of Opioid Dependence, Kills Leukemia Cells and Overcomes Chemoresistance
Cancer Res.,
August 1, 2008;
68(15):
6059 - 6064.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Friesen, M. Uhl, U. Pannicke, K. Schwarz, E. Miltner, and K.-M. Debatin
DNA-Ligase IV and DNA-Protein Kinase Play a Critical Role in Deficient Caspases Activation in Apoptosis-resistant Cancer Cells by Using Doxorubicin
Mol. Biol. Cell,
August 1, 2008;
19(8):
3283 - 3289.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A.G.M. Cillessen, C. J. Hess, E. Hooijberg, K. C.M. Castricum, P. Kortman, F. Denkers, W. Vos, M. A. van de Wiel, G. J. Schuurhuis, G. J. Ossenkoppele, et al.
Inhibition of the Intrinsic Apoptosis Pathway Downstream of Caspase-9 Activation Causes Chemotherapy Resistance in Diffuse Large B-Cell Lymphoma
Clin. Cancer Res.,
December 1, 2007;
13(23):
7012 - 7021.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. N. Reske, S. Deisenhofer, G. Glatting, B. D. Zlatopolskiy, A. Morgenroth, A. T. J. Vogg, A. K. Buck, and C. Friesen
123I-ITdU-Mediated Nanoirradiation of DNA Efficiently Induces Cell Kill in HL60 Leukemia Cells and in Doxorubicin-, {beta}-, or {gamma}-Radiation-Resistant Cell Lines
J. Nucl. Med.,
June 1, 2007;
48(6):
1000 - 1007.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bossard, K. Belhadj, F. Reyes, N. Martin-Garcia, F. Berger, J. A. Kummer, J. Briere, A.-C. Baglin, S. Cheze, J. Bosq, et al.
Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials
Blood,
March 1, 2007;
109(5):
2183 - 2189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. Meyer, L. Karawajew, M. Schrappe, W.-D. Ludwig, K.-M. Debatin, and K. Stahnke
Cytochrome c-related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL
Blood,
June 1, 2006;
107(11):
4524 - 4531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Su, J. Kuball, A.-P. Barreiros, D. Gottfried, E. A. Ferreira, M. Theobald, P. R. Galle, D. Strand, and S. Strand
Nitric Oxide Promotes Resistance to Tumor Suppression by CTLs
J. Immunol.,
April 1, 2006;
176(7):
3923 - 3930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Catley, Y.-T. Tai, R. Shringarpure, R. Burger, M. T. Son, K. Podar, P. Tassone, D. Chauhan, T. Hideshima, L. Denis, et al.
Proteasomal Degradation of Topoisomerase I Is Preceded by c-Jun NH2-Terminal Kinase Activation, Fas Up-Regulation, and Poly(ADP-Ribose) Polymerase Cleavage in SN38-Mediated Cytotoxicity against Multiple Myeloma
Cancer Res.,
December 1, 2004;
64(23):
8746 - 8753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Svingen, D. Loegering, J. Rodriquez, X. W. Meng, P. W. Mesner Jr., S. Holbeck, A. Monks, S. Krajewski, D. A. Scudiero, E. A. Sausville, et al.
Components of the Cell Death Machine and Drug Sensitivity of the National Cancer Institute Cell Line Panel
Clin. Cancer Res.,
October 15, 2004;
10(20):
6807 - 6820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. V. Oleinik and S. A. Krupenko
Ectopic Expression of 10-Formyltetrahydrofolate Dehydrogenase in A549 Cells Induces G1 Cell Cycle Arrest and Apoptosis
Mol. Cancer Res.,
June 1, 2003;
1(8):
577 - 588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J J Oudejans, R L ten Berge, and C J L M Meijer
Immune escape mechanisms in ALCL
J. Clin. Pathol.,
June 1, 2003;
56(6):
423 - 425.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Wittig, M. Nessling, R. D. Will, J. Mollenhauer, R. Salowsky, E. Munstermann, M. Schick, H. Helmbach, B. Gschwendt, B. Korn, et al.
Candidate Genes for Cross-Resistance against DNA-damaging Drugs
Cancer Res.,
November 15, 2002;
62(22):
6698 - 6705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. F. Dukers, C. J. L. M. Meijer, R. L. ten Berge, W. Vos, G. J. Ossenkoppele, and J. J. Oudejans
High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict favorable clinical outcome
Blood,
June 17, 2002;
100(1):
36 - 42.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. ten Berge, C. J. L. M. Meijer, D. F. Dukers, J. A. Kummer, B. A. Bladergroen, W. Vos, C. E. Hack, G. J. Ossenkoppele, and J. J. Oudejans
Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma
Blood,
May 29, 2002;
99(12):
4540 - 4546.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Los, M. Mozoluk, D. Ferrari, A. Stepczynska, C. Stroh, A. Renz, Z. Herceg, Z.-Q. Wang, and K. Schulze-Osthoff
Activation and Caspase-mediated Inhibition of PARP: A Molecular Switch between Fibroblast Necrosis and Apoptosis in Death Receptor Signaling
Mol. Biol. Cell,
March 1, 2002;
13(3):
978 - 988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Stahnke, S. Fulda, C. Friesen, G. Strau{beta}, and K.-M. Debatin
Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy
Blood,
November 15, 2001;
98(10):
3066 - 3073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Watts, B. W. Futscher, R. Isett, M. Gleason-Guzman, M. W. Kunkel, and S. E. Salmon
cDNA Microarray Analysis of Multidrug Resistance: Doxorubicin Selection Produces Multiple Defects in Apoptosis Signaling Pathways
J. Pharmacol. Exp. Ther.,
November 1, 2001;
299(2):
434 - 441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Herr and K.-M. Debatin
Cellular stress response and apoptosis in cancer therapy
Blood,
November 1, 2001;
98(9):
2603 - 2614.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Uzzo, V. Kolenko, C. J. Froelich, C. Tannenbaum, L. Molto, A. C. Novick, N. H. Bander, R. Bukowski, and J. H. Finke
The T Cell Death Knell: Immune-mediated Tumor Death in Renal Cell Carcinoma
Clin. Cancer Res.,
October 1, 2001;
7(10):
3276 - 3281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Renz, W. E. Berdel, M. Kreuter, C. Belka, K. Schulze-Osthoff, and M. Los
Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo
Blood,
September 1, 2001;
98(5):
1542 - 1548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Laurent and J.-P. Jaffrezou
Signaling pathways activated by daunorubicin
Blood,
August 15, 2001;
98(4):
913 - 924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Z. Carter, M. Milella, D. C. Altieri, and M. Andreeff
Cytokine-regulated expression of survivin in myeloid leukemia
Blood,
May 1, 2001;
97(9):
2784 - 2790.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Bellarosa, A. Ciucci, A. Bullo, F. Nardelli, S. Manzini, C. A. Maggi, and C. Goso
Apoptotic Events in a Human Ovarian Cancer Cell Line Exposed to Anthracyclines
J. Pharmacol. Exp. Ther.,
April 13, 2001;
296(2):
276 - 283.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
P. J. Frost, L. H. Butterfield, V. B. Dissette, J. S. Economou, and B. Bonavida
Immunosensitization of Melanoma Tumor Cells to Non-MHC Fas-Mediated Killing by MART-1-Specific CTL Cultures
J. Immunol.,
March 1, 2001;
166(5):
3564 - 3573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ochs and B. Kaina
Apoptosis Induced by DNA Damage O -Methylguanine Is Bcl-2 and Caspase-9/3 Regulated and Fas/Caspase-8 Independent
Cancer Res.,
October 1, 2000;
60(20):
5815 - 5824.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. G. Ferreira, C. Tolis, S. W. Span, G. J. Peters, T. van Lopik, A. J. Kummer, H. M. Pinedo, and G. Giaccone
Drug-induced Apoptosis in Lung Cancer Cells Is Not Mediated by the Fas/FasL (CD95/APO1) Signaling Pathway
Clin. Cancer Res.,
January 1, 2000;
6(1):
203 - 212.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Fulda, G. Strauss, E. Meyer, and K.-M. Debatin
Functional CD95 ligand and CD95 death-inducing signaling complex in activation-induced cell death and doxorubicin-induced apoptosis in leukemic T cells
Blood,
January 1, 2000;
95(1):
301 - 308.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Jarry, G Vallette, E Cassagnau, A Moreau, C Bou-Hanna, P Lemarre, E Letessier, J-C Le Neel, J-P Galmiche, and C L Laboisse
Interleukin 1 and interleukin 1beta converting enzyme (caspase 1) expression in the human colonic epithelial barrier. Caspase 1 downregulation in colon cancer
Gut,
August 1, 1999;
45(2):
246 - 251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Srivastava, C. Y. Sasaki, J. M. Hardwick, and D. L. Longo
Bcl-2-Mediated Drug Resistance: Inhibition of Apoptosis by Blocking Nuclear Factor of Activated T Lymphocytes (Nfat)-Induced FAS Ligand Transcription
J. Exp. Med.,
July 19, 1999;
190(2):
253 - 266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. H. Landowski, K. H. Shain, M. M. Oshiro, I. Buyuksal, J. S. Painter, and W. S. Dalton
Myeloma Cells Selected for Resistance to CD95-Mediated Apoptosis Are Not Cross-Resistant to Cytotoxic Drugs: Evidence for Independent Mechanisms of Caspase Activation
Blood,
July 1, 1999;
94(1):
265 - 274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Kolenko, R. G. Uzzo, R. Bukowski, N. H. Bander, A. C. Novick, E. D. Hsi, and J. H. Finke
Dead or Dying: Necrosis versus Apoptosis in Caspase-deficient Human RenalCell Carcinoma
Cancer Res.,
June 1, 1999;
59(12):
2838 - 2842.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. O'Connor, A. Strasser;, M. Bennett, K. Macdonald, S. Chan, J. P. Luzio, R. Simari, and P. Weissberg;
Fas, p53, and Apoptosis
Science,
May 28, 1999;
284(5419):
1431b - 1431.
[Full Text]
|
|
|
|
|
|
|
S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff
Anticancer Drugs Induce Caspase-8/FLICE Activation and Apoptosis in the Absence of CD95 Receptor/Ligand Interaction
Blood,
May 1, 1999;
93(9):
3053 - 3063.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Keane, S. A. Ettenberg, M. M. Nau, E. K. Russell, and S. Lipkowitz
Chemotherapy Augments TRAIL-induced Apoptosis in Breast Cell Lines
Cancer Res.,
February 1, 1999;
59(3):
734 - 741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Fulda, C. Scaffidi, S. A. Susin, P. H. Krammer, G. Kroemer, M. E. Peter, and K.-M. Debatin
Activation of Mitochondria and Release of Mitochondrial Apoptogenic Factors by Betulinic Acid
J. Biol. Chem.,
December 18, 1998;
273(51):
33942 - 33948.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Evan and T. Littlewood
A Matter of Life and Cell Death
Science,
August 28, 1998;
281(5381):
1317 - 1322.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
I. Jeremias, C. Kupatt, B. Baumann, I. Herr, T. Wirth, and K.M. Debatin
Inhibition of Nuclear Factor kappa B Activation Attenuates Apoptosis Resistance in Lymphoid Cells
Blood,
June 15, 1998;
91(12):
4624 - 4631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Beltinger, E. Kurz, T. Bohler, M. Schrappe, W.-D. Ludwig, and K.-M. Debatin
CD95 (APO-1/Fas) Mutations in Childhood T-Lineage Acute Lymphoblastic Leukemia
Blood,
May 15, 1998;
91(10):
3943 - 3951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
