|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2893-2898
8Cl-cAMP Cytotoxicity in Both Steroid Sensitive and Insensitive
Multiple Myeloma Cell Lines Is Mediated by 8Cl-Adenosine
Robert G. Halgren,
Ann E. Traynor,
Shafali Pillay,
Joann L. Zell,
Kimberly F. Heller,
Nancy L. Krett, and
Steven T. Rosen
From the Lurie Comprehensive Cancer Center and Department of
Medicine, Northwestern University, Chicago, IL.
We have examined the cytotoxic effects of cyclic
adenosine-3 ,5-monophosphate (cAMP) derivatives on
multiple myeloma cells lines and determined that the 8-Chloro
substituted derivative (8Cl-cAMP) is one of the most potent. We report
here that 8Cl-cAMP is cytotoxic to both steroid sensitive and
insensitive myeloma cells with a half maximal concentration of
approximately 3 µmol/L. 8Cl-cAMP toxicity in myeloma cells is
dependent on phosphodiesterase activity in the serum of cell culture
medium. A metabolite of 8Cl-cAMP, 8-Chloro-adenosine (8Cl-AD), kills
myeloma cells as effectively as 8Cl-cAMP. Adenosine deaminase (ADA)
converts 8Cl-AD into 8Cl-inosine and abrogates the cytotoxic effects of
8Cl-cAMP, 8Cl-AMP, and 8Cl-AD, as does 5-(p-Nitrobenzyl)-6-Thio-Inosine (NBTI), an inhibitor of nucleoside uptake. These data
suggest that 8Cl-cAMP must be converted to 8Cl-AD and that 8Cl-AD is
the compound that enters the cell. Contrary to glucocorticoid-mediated cell death in myeloma cells, the pathway of 8Cl-AD-mediated cell death
appears to be independent of interleukin-6 (IL-6) actions. Although the
exact mode of action for this agent is currently unknown, its ability
to kill steroid sensitive and insensitive multiple myeloma cells in an
IL-6 independent fashion may offer exciting new therapeutic options.
© 1998 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:
|
|
|
|
 
A. J. Robinson-White, H.-P. Hsiao, W. W. Leitner, E. Greene, A. Bauer, N. L. Krett, M. Nesterova, and C. A. Stratakis
Protein Kinase A-Independent Inhibition of Proliferation and Induction of Apoptosis in Human Thyroid Cancer Cells by 8-Cl-Adenosine
J. Clin. Endocrinol. Metab.,
March 1, 2008;
93(3):
1020 - 1029.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Zhang, A. C. Zambon, K. Vranizan, K. Pothula, B. R. Conklin, and P. A. Insel
Gene Expression Signatures of cAMP/Protein Kinase A (PKA)-promoted, Mitochondrial-dependent Apoptosis: COMPARATIVE ANALYSIS OF WILD-TYPE AND cAMP-DEATHLESS S49 LYMPHOMA CELLS
J. Biol. Chem.,
February 15, 2008;
283(7):
4304 - 4313.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Stellrecht, C. J. Phillip, F. Cervantes-Gomez, and V. Gandhi
Multiple Myeloma Cell Killing by Depletion of the MET Receptor Tyrosine Kinase
Cancer Res.,
October 15, 2007;
67(20):
9913 - 9920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-H. Ahn, J. M. Jung, and S. H. Hong
8-Chloro-Cyclic AMP-Induced Growth Inhibition and Apoptosis Is Mediated by p38 Mitogen-Activated Protein Kinase Activation in HL60 Cells
Cancer Res.,
June 1, 2005;
65(11):
4896 - 4901.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Balakrishnan, C. M. Stellrecht, D. Genini, M. Ayres, W. G. Wierda, M. J. Keating, L. M. Leoni, and V. Gandhi
Cell death of bioenergetically compromised and transcriptionally challenged CLL lymphocytes by chlorinated ATP
Blood,
June 1, 2005;
105(11):
4455 - 4462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ghias, C. Ma, V. Gandhi, L. C. Platanias, N. L. Krett, and S. T. Rosen
8-Amino-adenosine induces loss of phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, and Akt kinase: Role in induction of apoptosis in multiple myeloma
Mol. Cancer Ther.,
April 1, 2005;
4(4):
569 - 577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. Krett, K. M. Davies, M. Ayres, C. Ma, C. Nabhan, V. Gandhi, and S. T. Rosen
8-Amino-adenosine is a potential therapeutic agent for multiple myeloma
Mol. Cancer Ther.,
November 1, 2004;
3(11):
1411 - 1420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Chen and T. L. Sheppard
Chain Termination and Inhibition of Saccharomyces cerevisiae Poly(A) Polymerase by C-8-modified ATP Analogs
J. Biol. Chem.,
September 24, 2004;
279(39):
40405 - 40411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Shih, S. Zhang, H. J. Cao, H.-Y. Tang, F. B. Davis, P. J. Davis, and H.-Y. Lin
Disparate Effects of Thyroid Hormone on Actions of Epidermal Growth Factor and Transforming Growth Factor-{alpha} Are Mediated by 3',5'-Cyclic Adenosine 5'-Monophosphate-Dependent Protein Kinase II
Endocrinology,
April 1, 2004;
145(4):
1708 - 1717.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Stellrecht, C. O. Rodriguez Jr., M. Ayres, and V. Gandhi
RNA-Directed Actions of 8-Chloro-Adenosine in Multiple Myeloma Cells
Cancer Res.,
November 15, 2003;
63(22):
7968 - 7974.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Gandhi, M. Ayres, R. G. Halgren, N. L. Krett, R. A. Newman, and S. T. Rosen
8-Chloro-cAMP and 8-Chloro-adenosine Act by the Same Mechanism in Multiple Myeloma Cells
Cancer Res.,
July 1, 2001;
61(14):
5474 - 5479.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
