|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 1075-1085
P-Glycoprotein Protects Leukemia Cells Against Caspase-Dependent,
but not Caspase-Independent, Cell Death
Ricky W. Johnstone,
Erika Cretney, and
Mark J. Smyth
From The Austin Research Institute, Austin Hospital, Heidelberg,
Victoria, Australia.
A major problem with treating patients with cancer by traditional
chemotherapeutic regimes is that their tumors often develop a multidrug
resistant (MDR) phenotype and subsequently become insensitive to
a range of different chemotoxic drugs. One cause of MDR is
overexpression of the drug-effluxing protein, P-glycoprotein.It is now apparent that P-glycoprotein may also possess a more generic antiapoptotic function that protects P-glycoprotein-expressing cancer
cells and normal cells from cell death. Herein we show that cells
induced to express P-glycoprotein either by drug selection or by
retroviral gene transduction with MDR1 cDNA are resistant to cell death
induced by a wide range of death stimuli, such as FasL, tumor necrosis
factor (TNF), and ultraviolet (UV) irradiation, that activate the
caspase apoptotic cascade.However, P-glycoprotein-expressing cells were not resistant to caspase-independent cell death mediated by
pore-forming proteins and granzyme B.MDR
P-glycoprotein-expressing cells were made sensitive to
caspase-dependent apoptosis by the addition of anti-P-glycoprotein
antibodies or verapamil, a pharmacological inhibitor of P-glycoprotein
function. Clonogenic assays showed that P-glycoprotein confers
long-term resistance to caspase-dependent apoptotic stimuli but not to
caspase-independent cell death stimuli. This study has confirmed a
potential novel physiological function for P-glycoprotein and it now
remains to dissect the molecular mechanisms involved in the inhibition
of capsase-dependent cell death by P-glycoprotein.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
W. Lee, A. Belkhiri, A. C. Lockhart, N. Merchant, H. Glaeser, E. I. Harris, M. K. Washington, E. M. Brunt, A. Zaika, R. B. Kim, et al.
Overexpression of OATP1B3 Confers Apoptotic Resistance in Colon Cancer
Cancer Res.,
December 15, 2008;
68(24):
10315 - 10323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nguyen, R. C. Marcellus, A. Roulston, M. Watson, L. Serfass, S. R. Murthy Madiraju, D. Goulet, J. Viallet, L. Belec, X. Billot, et al.
Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis
PNAS,
December 4, 2007;
104(49):
19512 - 19517.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Challen and M. H. Little
A Side Order of Stem Cells: The SP Phenotype.
Stem Cells,
January 1, 2006;
24(1):
3 - 12.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Tian, V. Jurukovski, X.-P. Wang, M. H. Kaplan, and H. Xu
Epigenetic Regulation of WTH3 in Primary and Cultured Drug-Resistant Breast Cancer Cells
Cancer Res.,
November 1, 2005;
65(21):
10024 - 10031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Tian, V. Jurukovski, L. Yuan, J. Shan, and H. Xu
WTH3, which Encodes a Small G Protein, Is Differentially Regulated in Multidrug-Resistant and Sensitive MCF7 Cells
Cancer Res.,
August 15, 2005;
65(16):
7421 - 7428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Lazarowski, H. J. Garcia Rivello, G. L. Vera Janavel, L. A. Cuniberti, P. M. Cabeza Meckert, G. G. Yannarelli, A. Mele, A. J. Crottogini, and R. P. Laguens
Cardiomyocytes of Chronically Ischemic Pig Hearts Express the MDR-1 Gene-encoded P-glycoprotein
J. Histochem. Cytochem.,
July 1, 2005;
53(7):
845 - 850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mahadevan and A. F. List
Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies
Blood,
October 1, 2004;
104(7):
1940 - 1951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. S. Cummings, G. R. Kinsey, L. J. C. Bolchoz, and R. G. Schnellmann
Identification of Caspase-Independent Apoptosis in Epithelial and Cancer Cells
J. Pharmacol. Exp. Ther.,
July 1, 2004;
310(1):
126 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhong and A. R. Safa
RNA Helicase A in the MEF1 Transcription Factor Complex Up-regulates the MDR1 Gene in Multidrug-resistant Cancer Cells
J. Biol. Chem.,
April 23, 2004;
279(17):
17134 - 17141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Geromin, J.-F. Bourge, A. Soulie, R. Pawliuk, C. Fleet, E. Michel, Y. Denizot, C. Berthou, P. Leboulch, F. Sigaux, et al.
Glycoprotein 170 Induces Platelet-Activating Factor Receptor Membrane Expression and Confers Tumor Cell Hypersensitivity to NK-Dependent Cell Lysis
J. Immunol.,
March 15, 2004;
172(6):
3604 - 3611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kankesan, A. Yusuf, E. Laconi, R. Vanama, G. Bradley, J. J. Thiessen, V. Ling, P. M. Rao, S. Rajalakshmi, and D. S. R. Sarma
Effect of PSC 833, an inhibitor of P-glycoprotein, on 1,2-dimethylhydrazine-induced liver carcinogenesis in rats
Carcinogenesis,
December 1, 2003;
24(12):
1977 - 1984.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Solary, B. Drenou, L. Campos, P. de Cremoux, F. Mugneret, P. Moreau, B. Lioure, A. Falkenrodt, B. Witz, M. Bernard, et al.
Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia
Blood,
August 15, 2003;
102(4):
1202 - 1210.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Peart, K. M. Tainton, A. A. Ruefli, A. E. Dear, K. A. Sedelies, L. A. O'Reilly, N. J. Waterhouse, J. A. Trapani, and R. W. Johnstone
Novel Mechanisms of Apoptosis Induced by Histone Deacetylase Inhibitors
Cancer Res.,
August 1, 2003;
63(15):
4460 - 4471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J E Ros, T A D Roskams, M Geuken, R Havinga, P L Splinter, B E Petersen, N F LaRusso, D M van der Kolk, F Kuipers, K N Faber, et al.
ATP binding cassette transporter gene expression in rat liver progenitor cells
Gut,
July 1, 2003;
52(7):
1060 - 1067.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Liu, H. Huang, X. Lu, M. Golinski, S. Comesse, D. Watt, R. B. Grossman, and J. A. Moscow
Down-Regulation of Thiamine Transporter THTR2 Gene Expression in Breast Cancer and Its Association With Resistance to Apoptosis
Mol. Cancer Res.,
July 1, 2003;
1(9):
665 - 673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Good, M. Cabral, S. Sharma, J. Yang, N. Van Driessche, C. A. Shaw, G. Shaulsky, and A. Kuspa
TagA, a putative serine protease/ABC transporter of Dictyostelium that is required for cell fate determination at the onset of development
Development,
July 1, 2003;
130(13):
2953 - 2965.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Aleman, J.-P. Annereau, X.-J. Liang, C. O. Cardarelli, B. Taylor, J. J. Yin, A. Aszalos, and M. M. Gottesman
P-Glycoprotein, Expressed in Multidrug Resistant Cells, Is Not Responsible for Alterations in Membrane Fluidity or Membrane Potential
Cancer Res.,
June 15, 2003;
63(12):
3084 - 3091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mufti, A. F. List, S. D. Gore, and A. Y.L. Ho
Myelodysplastic Syndrome
Hematology,
January 1, 2003;
2003(1):
176 - 199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. van der Kolk, E. Vellenga, G. L. Scheffer, M. Muller, S. E. Bates, R. J. Scheper, and E. G. E. de Vries
Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia
Blood,
May 15, 2002;
99(10):
3763 - 3770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U Potocnik, M Ravnik-Glavac, R Golouh, and D Glavac
Naturally occurring mutations and functional polymorphisms in multidrug resistance 1 gene: correlation with microsatellite instability and lymphoid infiltration in colorectal cancers
J. Med. Genet.,
May 1, 2002;
39(5):
340 - 346.
[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]
|
|
|
|
|
|
|
A. A. Ruefli, M. J. Ausserlechner, D. Bernhard, V. R. Sutton, K. M. Tainton, R. Kofler, M. J. Smyth, and R. W. Johnstone
The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species
PNAS,
September 4, 2001;
(2001)
191208598.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Scotto and R. A. Johnson
Transcription of MDR1: A Therapeutic Target
Mol. Interv.,
June 1, 2001;
1(2):
117 - 125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Johnstone, M. Gerber, T. Landewe, A. Tollefson, W. S. Wold, and A. Shilatifard
Functional Analysis of the Leukemia Protein ELL: Evidence for a Role in the Regulation of Cell Growth and Survival
Mol. Cell. Biol.,
March 1, 2001;
21(5):
1672 - 1681.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
O. Legrand, J.-Y. Perrot, G. Simonin, M. Baudard, and J.-P. Marie
JC-1: a very sensitive fluorescent probe to test Pgp activity in adult acute myeloid leukemia
Blood,
January 15, 2001;
97(2):
502 - 508.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yamada, A. S. Takaoka, Y. Naishiro, R. Hayashi, K. Maruyama, C. Maesawa, A. Ochiai, and S. Hirohashi
Transactivation of the Multidrug Resistance 1 Gene by T-Cell Factor 4/{beta}-Catenin Complex in Early Colorectal Carcinogenesis
Cancer Res.,
September 1, 2000;
60(17):
4761 - 4766.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. D. Bunting, S. Zhou, T. Lu, and B. P. Sorrentino
Enforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo
Blood,
August 1, 2000;
96(3):
902 - 909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jin, B. Gorfajn, G. Faircloth, and K. W. Scotto
Ecteinascidin 743, a transcription-targeted chemotherapeutic that inhibits MDR1 activation
PNAS,
June 6, 2000;
97(12):
6775 - 6779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Ruth and I. B. Roninson
Effects of the Multidrug Transporter P-Glycoprotein on Cellular Responses to Ionizing Radiation
Cancer Res.,
May 1, 2000;
60(10):
2576 - 2578.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Pallis and N. Russell
P-glycoprotein plays a drug-efflux-independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modulation of a sphingomyelin-ceramide apoptotic pathway
Blood,
May 1, 2000;
95(9):
2897 - 2904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Ponzanelli, M. Gianni, R. Giavazzi, A. Garofalo, I. Nicoletti, U. Reichert, E. Erba, A. Rambaldi, M. Terao, and E. Garattini
Isolation and characterization of an acute promyelocytic leukemia cell line selectively resistant to the novel antileukemic and apoptogenic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid
Blood,
April 15, 2000;
95(8):
2672 - 2682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Ruefli, M. J. Smyth, and R. W. Johnstone
HMBA induces activation of a caspase-independent cell death pathway to overcome P-glycoprotein-mediated multidrug resistance
Blood,
April 1, 2000;
95(7):
2378 - 2385.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Hu, S. Jin, and K. W. Scotto
Transcriptional Activation of the MDR1 Gene by UV Irradiation. ROLE OF NF-Y AND Sp1
J. Biol. Chem.,
January 28, 2000;
275(4):
2979 - 2985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-A. Ghetie, V. Ghetie, and E. S. Vitetta
Anti-CD19 Antibodies Inhibit the Function of the P-gp Pump in Multidrug-resistant B Lymphoma Cells
Clin. Cancer Res.,
December 1, 1999;
5(12):
3920 - 3927.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Johnstone, K. M. Tainton, A. A. Ruefli, C. J. Froelich, L. Cerruti, S. M. Jane, and M. J. Smyth
P-glycoprotein Does Not Protect Cells against Cytolysis Induced by Pore-forming Proteins
J. Biol. Chem.,
May 11, 2001;
276(20):
16667 - 16673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wartenberg, F. C. Ling, M. Schallenberg, A. T. Baumer, K. Petrat, J. Hescheler, and H. Sauer
Down-regulation of Intrinsic P-glycoprotein Expression in Multicellular Prostate Tumor Spheroids by Reactive Oxygen Species
J. Biol. Chem.,
May 11, 2001;
276(20):
17420 - 17428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Ruefli, M. J. Ausserlechner, D. Bernhard, V. R. Sutton, K. M. Tainton, R. Kofler, M. J. Smyth, and R. W. Johnstone
The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species
PNAS,
September 11, 2001;
98(19):
10833 - 10838.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
