|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 October 2001, Vol. 98, No. 7, pp. 2183-2192
NEOPLASIA
Apo2L/TRAIL and Bcl-2-related proteins regulate type I
interferon-induced apoptosis in multiple myeloma
Quan Chen,
Bendi Gong,
Ashraf S. Mahmoud-Ahmed,
Aimin Zhou,
Eric D. Hsi,
Mohamad Hussein, and
Alexandru Almasan
From the Department of Cancer Biology, Lerner Research
Institute; the Department of Clinical Pathology; the Myeloma Program;
the Department of Radiation Oncology; the Taussig Cancer Center; and
The Cleveland Clinic Foundation, Cleveland, OH.
It has been reported that interferons (IFNs) may have antitumor
activity in multiple myeloma (MM). The mechanism for their effect on
MM, however, remains elusive. This study shows that IFN- and - ,
but not - , induce apoptosis characterized by Annexin V positivity,
nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from
10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one
of the earliest events following IFN administration in U266 cells.
Treatment of these cells with TRAIL, but not with Fas agonistic
antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in
U266 cells was partially blocked by a dominant-negative Apo2L receptor,
DR5, demonstrating the functional significance of Apo2L induction. This
study shows that IFNs activate caspases and the mitochondrial-dependent
apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-
and - induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late,
amplified cytochrome c release coincides with changes in levels of
Bcl-2, Bcl-XL, and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of
Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs
and Apo2L induce cell death of CD38+/CD45 /dim
plasma cells, without significant effect on nonplasma blood cells, in a
caspase and Bcl-2 cleavage-dependent manner. These results warrant
further clinical studies with IFNs and Apo2L in MM.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. I. Bussiere, R. Chaturvedi, M. Asim, K. L. Hoek, Y. Cheng, J. Gainor, A. Scholz, W. N. Khan, and K. T. Wilson
Low Multiplicity of Infection of Helicobacter pylori Suppresses Apoptosis of B Lymphocytes.
Cancer Res.,
July 1, 2006;
66(13):
6834 - 6842.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Gamero, R. Potla, J. Wegrzyn, M. Szelag, A. E. Edling, K. Shimoda, D. C. Link, J. Dulak, D. P. Baker, Y. Tanabe, et al.
Activation of Tyk2 and Stat3 Is Required for the Apoptotic Actions of Interferon-beta in Primary Pro-B Cells
J. Biol. Chem.,
June 16, 2006;
281(24):
16238 - 16244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Hu, M. E. Mancl, and B. J. Barnes
Signaling through IFN Regulatory Factor-5 Sensitizes p53-Deficient Tumors to DNA Damage-Induced Apoptosis and Cell Death
Cancer Res.,
August 15, 2005;
65(16):
7403 - 7412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. Streck, P. V. Dickson, C. Y.C. Ng, J. Zhou, J. T. Gray, A. C. Nathwani, and A. M. Davidoff
Adeno-Associated Virus Vector-Mediated Systemic Delivery of IFN-{beta} Combined with Low-Dose Cyclophosphamide Affects Tumor Regression in Murine Neuroblastoma Models
Clin. Cancer Res.,
August 15, 2005;
11(16):
6020 - 6029.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Y. Dimberg, A. I. Dimberg, K. Ivarsson, T. Stromberg, A. Osterborg, K. Nilsson, F. Oberg, and H. J. Wiklund
Ectopic and IFN-induced expression of Fas overcomes resistance to Fas-mediated apoptosis in multiple myeloma cells
Blood,
August 15, 2005;
106(4):
1346 - 1354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Sun and D. W. Leaman
Involvement of Noxa in Cellular Apoptotic Responses to Interferon, Double-stranded RNA, and Virus Infection
J. Biol. Chem.,
April 22, 2005;
280(16):
15561 - 15568.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Matsuda, A. Almasan, M. Tomita, K. Tamaki, M. Saito, M. Tadano, H. Yagita, T. Ohta, and N. Mori
Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand
J. Gen. Virol.,
April 1, 2005;
86(4):
1055 - 1065.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Evens, P. Lecane, D. Magda, S. Prachand, S. Singhal, J. Nelson, R. A. Miller, R. B. Gartenhaus, and L. I. Gordon
Motexafin gadolinium generates reactive oxygen species and induces apoptosis in sensitive and highly resistant multiple myeloma cells
Blood,
February 1, 2005;
105(3):
1265 - 1273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Crowder, O. Dahle, R. E. Davis, O. S. Gabrielsen, and S. Rudikoff
PML mediates IFN-{alpha}-induced apoptosis in myeloma by regulating TRAIL induction
Blood,
February 1, 2005;
105(3):
1280 - 1287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Papageorgiou, L. Lashinger, R. Millikan, H. B. Grossman, W. Benedict, C. P. N. Dinney, and D. J. McConkey
Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Interferon-Induced Apoptosis in Human Bladder Cancer Cells
Cancer Res.,
December 15, 2004;
64(24):
8973 - 8979.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Colucci, G. Brunetti, R. Rizzi, A. Zonno, G. Mori, G. Colaianni, D. Del Prete, R. Faccio, A. Liso, S. Capalbo, et al.
T cells support osteoclastogenesis in an in vitro model derived from human multiple myeloma bone disease: the role of the OPG/TRAIL interaction
Blood,
December 1, 2004;
104(12):
3722 - 3730.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hideshima, P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson
Advances in biology of multiple myeloma: clinical applications
Blood,
August 1, 2004;
104(3):
607 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Thyrell, L. Hjortsberg, V. Arulampalam, T. Panaretakis, S. Uhles, M. Dagnell, B. Zhivotovsky, I. Leibiger, D. Grander, and K. Pokrovskaja
Interferon {alpha}-induced Apoptosis in Tumor Cells Is Mediated through the Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Signaling Pathway
J. Biol. Chem.,
June 4, 2004;
279(23):
24152 - 24162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Evens, S. Prachand, B. Shi, M. Paniaqua, L. I. Gordon, and R. B. Gartenhaus
Imexon-Induced Apoptosis in Multiple Myeloma Tumor Cells Is Caspase-8 Dependent
Clin. Cancer Res.,
February 15, 2004;
10(4):
1481 - 1491.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Younes and M. E. Kadin
Emerging Applications of the Tumor Necrosis Factor Family of Ligands and Receptors in Cancer Therapy
J. Clin. Oncol.,
September 15, 2003;
21(18):
3526 - 3534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Greil, G. Anether, K. Johrer, and I. Tinhofer
Tracking death dealing by Fas and TRAIL in lymphatic neoplastic disorders: pathways, targets, and therapeutic tools
J. Leukoc. Biol.,
September 1, 2003;
74(3):
311 - 330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ray and A. Almasan
Apoptosis Induction in Prostate Cancer Cells and Xenografts by Combined Treatment with Apo2 Ligand/Tumor Necrosis Factor-related Apoptosis-inducing Ligand and CPT-11
Cancer Res.,
August 1, 2003;
63(15):
4713 - 4723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Uno, T. Inukai, N. Kayagaki, K. Goi, H. Sato, A. Nemoto, K. Takahashi, K. Kagami, N. Yamaguchi, H. Yagita, et al.
TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells
Blood,
May 1, 2003;
101(9):
3658 - 3667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Secchiero, A. Gonelli, G. Ciabattoni, E. Melloni, V. Grill, B. Rocca, G. Delbello, and G. Zauli
TNF-related apoptosis-inducing ligand (TRAIL) up-regulates cyclooxygenase (COX)-1 activity and PGE2 production in cells of the myeloid lineage
J. Leukoc. Biol.,
November 1, 2002;
72(5):
986 - 994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Spencer, S.-L. Yeh, K. Koutrevelis, C. Baulch-Brown ;, N. Mitsiades, C. Mitsiades, K. C. Anderson, and S. P. Treon
TRAIL-induced apoptosis of authentic myeloma cells does not correlate with the procaspase-8/cFLIP ratio
Blood,
September 26, 2002;
100(8):
3049 - 3050.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Secchiero, A. Gonelli, P. Mirandola, E. Melloni, L. Zamai, C. Celeghini, D. Milani, and G. Zauli
Tumor necrosis factor-related apoptosis-inducing ligand induces monocytic maturation of leukemic and normal myeloid precursors through a caspase-dependent pathway
Blood,
September 18, 2002;
100(7):
2421 - 2429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Leaman, M. Chawla-Sarkar, K. Vyas, M. Reheman, K. Tamai, S. Toji, and E. C. Borden
Identification of X-linked Inhibitor of Apoptosis-associated Factor-1 as an Interferon-stimulated Gene That Augments TRAIL Apo2L-induced Apoptosis
J. Biol. Chem.,
August 2, 2002;
277(32):
28504 - 28511.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Chawla-Sarkar, D. W. Leaman, B. S. Jacobs, and E. C. Borden
IFN-{beta} Pretreatment Sensitizes Human Melanoma Cells to TRAIL/Apo2 Ligand-Induced Apoptosis
J. Immunol.,
July 15, 2002;
169(2):
847 - 855.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Chacko, X. Ma, and M. L. Adamo
Double-Stranded Ribonucleic Acid Decreases C6 Rat Glioma Cell Proliferation in Part by Activating Protein Kinase R and Decreasing Insulin-Like Growth Factor I Levels
Endocrinology,
June 1, 2002;
143(6):
2144 - 2154.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
