|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 1045-1061
The Novel Synthetic Retinoid
6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene Carboxylic Acid (CD437)
Causes Apoptosis in Acute Promyelocytic Leukemia Cells Through Rapid
Activation of Caspases
Luca Mologni,
Isabella Ponzanelli,
Filippo Bresciani,
Gabriele Sardiello,
Daniele Bergamaschi,
Maurizio Gianní,
Uwe Reichert,
Alessandro Rambaldi,
Mineko Terao, and
Enrico Garattini
From the Laboratory of Molecular Biology, Centro Catullo e Daniela
Borgomainerio, Laboratory of Cancer Chemotherapy, Istituto di Ricerche
Farmacologiche "Mario Negri," Milano, Italy; GALDERMA Research
and Development, Sophia Antipolis; and the Divisione di Ematologia,
Ospedali Riuniti di Bergamo, Bergamo, Italy.
The synthetic retinoid
6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid
(CD437), which was originally developed as an retinoic acid receptor
(RAR)- agonist, induces rapid apoptosis in all-trans retinoic acid
(ATRA)-sensitive and ATRA-resistant clones of the NB4 cell line, a
widely used experimental model of acute promyelocytic leukemia (APL).
In addition, the compound is apoptogenic in primary cultures of freshly
isolated APL blasts obtained from a newly diagnosed case and an
ATRA-resistant relapsed patient. NB4 cells in the S-phase of the cycle
are most sensitive to CD437-triggered apoptosis. CD437-dependent
apoptosis does not require de novo protein synthesis and activation of
RAR- or any of the other nuclear retinoic acid receptors. The
process is preceded by rapid activation of a caspase-like enzymatic
activity capable of cleaving the fluorogenic DEVD but not the
fluorogenic YVAD tetrapeptide. Increased caspase activity correlates
with caspase-3 and caspase-7 activation. Inhibition of caspases by
z-VAD suppresses the nuclear DNA degradation observed in NB4 cells
treated with CD437, as well as the degradation of pro-caspase-3 and
pro-caspase-7. CD437-dependent activation of caspases is preceded by
release of cytochrome c from the mitochondria into the cytosol of
treated cells. Leakage of cytochrome c lays upstream of caspase
activation, because the phenomenon is left unaffected by pretreatment
of NB4 cells with z-VAD. Treatment of APL cells with CD437 is
associated with a caspase-dependent degradation of
promyelocytic leukemia-RAR- , which can be completely
inhibited by z-VAD.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Farhana, M. I. Dawson, L. Xu, and J. A. Fontana
SHP and Sin3A expression are essential for adamantyl-substituted retinoid-related molecule-mediated nuclear factor-{kappa}B activation, c-Fos/c-Jun expression, and cellular apoptosis
Mol. Cancer Ther.,
June 1, 2009;
8(6):
1625 - 1635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Valli, G. Paroni, A. M. Di Francesco, R. Riccardi, M. Tavecchio, E. Erba, A. Boldetti, M. Gianni', M. Fratelli, C. Pisano, et al.
Atypical retinoids ST1926 and CD437 are S-phase-specific agents causing DNA double-strand breaks: significance for the cytotoxic and antiproliferative activity
Mol. Cancer Ther.,
September 1, 2008;
7(9):
2941 - 2954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Farhana, M. I. Dawson, M. Leid, L. Wang, D. D. Moore, G. Liu, Z. Xia, and J. A. Fontana
Adamantyl-Substituted Retinoid-Related Molecules Bind Small Heterodimer Partner and Modulate the Sin3A Repressor
Cancer Res.,
January 1, 2007;
67(1):
318 - 325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Parrella, M. Gianni, M. Fratelli, M. M. Barzago, I. Raska Jr, L. Diomede, M. Kurosaki, C. Pisano, P. Carminati, L. Merlini, et al.
Antitumor Activity of the Retinoid-Related Molecules (E)-3-(4'-Hydroxy-3'-adamantylbiphenyl-4-yl)acrylic Acid (ST1926) and 6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalene Carboxylic Acid (CD437) in F9 Teratocarcinoma: Role of Retinoic Acid Receptor {gamma} and Retinoid-Independent Pathways
Mol. Pharmacol.,
September 1, 2006;
70(3):
909 - 924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Harris, B. Ozpolat, F. Abdi, S. Gu, A. Legler, K. G. Mawuenyega, M. Tirado-Gomez, G. Lopez-Berestein, and X. Chen
Comparative proteomic analysis of all-trans-retinoic acid treatment reveals systematic posttranscriptional control mechanisms in acute promyelocytic leukemia
Blood,
September 1, 2004;
104(5):
1314 - 1323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Bayon, M. A. Ortiz, F. J. Lopez-Hernandez, P. H. Howe, and F. J. Piedrafita
The Retinoid Antagonist MX781 Induces Clusterin Expression in Prostate Cancer Cells via Heat Shock Factor-1 and Activator Protein-1 Transcription Factors
Cancer Res.,
August 15, 2004;
64(16):
5905 - 5912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Keedwell, Y. Zhao, L. A. Hammond, S. Qin, K.-Y. Tsang, A. Reitmair, Y. Molina, Y. Okawa, L. I. Atangan, D.-L. Shurland, et al.
A Retinoid-Related Molecule that Does Not Bind to Classical Retinoid Receptors Potently Induces Apoptosis in Human Prostate Cancer Cells through Rapid Caspase Activation
Cancer Res.,
May 1, 2004;
64(9):
3302 - 3312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Garattini, E. Parrella, L. Diomede, M. Gianni', Y. Kalac, L. Merlini, D. Simoni, R. Zanier, F. F. Ferrara, I. Chiarucci, et al.
ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis
Blood,
January 1, 2004;
103(1):
194 - 207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Garattini
New approaches to cancer therapy
Ann. Onc.,
June 1, 2003;
14(6):
813 - 816.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. Lopez-Hernandez, M. A. Ortiz, Y. Bayon, and F. J. Piedrafita
Z-FA-fmk Inhibits Effector Caspases but not Initiator Caspases 8 and 10, and Demonstrates That Novel Anticancer Retinoid-related Molecules Induce Apoptosis via the Intrinsic Pathway
Mol. Cancer Ther.,
March 1, 2003;
2(3):
255 - 263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. F. Holmes, D. R. Soprano, and K. J. Soprano
Elucidation of Molecular Events Mediating Induction of Apoptosis by Synthetic Retinoids Using a CD437-resistant Ovarian Carcinoma Cell Line
J. Biol. Chem.,
November 15, 2002;
277(47):
45408 - 45419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pisano, P. Kollar, M. Gianni, Y. Kalac, V. Giordano, F. F. Ferrara, R. Tancredi, A. Devoto, A. Rinaldi, A. Rambaldi, et al.
Bis-indols: a novel class of molecules enhancing the cytodifferentiating properties of retinoids in myeloid leukemia cells
Blood,
November 15, 2002;
100(10):
3719 - 3730.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Garattini, M. Gianni', M. Terao, and H. K. Parekh
Correspondence re: A. Kumar et al., Cross-Resistance to the Synthetic Retinoid CD437 in a Paclitaxel-resistant Human Ovarian Carcinoma Cell Line Is Independent of the Overexpression of Retinoic Acid Receptor-{gamma}. Cancer Res., 61: 7552-7555, 2001.
Cancer Res.,
April 1, 2002;
62(7):
2192 - 2194.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gianni', Y. Kalac, I. Ponzanelli, A. Rambaldi, M. Terao, and E. Garattini
Tyrosine kinase inhibitor STI571 potentiates the pharmacologic activity of retinoic acid in acute promyelocytic leukemia cells: effects on the degradation of RAR{alpha} and PML-RAR{alpha}
Blood,
May 15, 2001;
97(10):
3234 - 3243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Babina, K. Mammeri, and B. M. Henz
Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion--evidence for retinoid signaling pathways in the mast cell lineage
J. Leukoc. Biol.,
March 1, 2001;
69(3):
361 - 372.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S.-Y. Sun, P. Yue, R. A. S. Chandraratna, Y. Tesfaigzi, W. K. Hong, and R. Lotan
Dual Mechanisms of Action of the Retinoid CD437: Nuclear Retinoic Acid Receptor-Mediated Suppression of Squamous Differentiation and Receptor-Independent Induction of Apoptosis in UMSCC22B Human Head and Neck Squamous Cell Carcinoma Cells
Mol. Pharmacol.,
September 1, 2000;
58(3):
508 - 514.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
P. le Coutre, E. Tassi, M. Varella-Garcia, R. Barni, L. Mologni, G. Cabrita, E. Marchesi, R. Supino, and C. Gambacorti-Passerini
Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification
Blood,
March 1, 2000;
95(5):
1758 - 1766.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Le Doze, D. Debruyne, F. Albessard, L. Barre, and G. L. Defer
Pharmacokinetics of All-trans Retinoic Acid, 13-cis Retinoic Acid, and Fenretinide in Plasma and Brain of Rat
Drug Metab. Dispos.,
February 1, 2000;
28(2):
205 - 208.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
P. Marchetti, N. Zamzami, B. Joseph, S. Schraen-Maschke, C. Mereau-Richard, P. Costantini, D. Metivier, S. A. Susin, G. Kroemer, and P. Formstecher
The Novel Retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene Carboxylic Acid Can Trigger Apoptosis through a Mitochondrial Pathway Independent of the Nucleus
Cancer Res.,
December 1, 1999;
59(24):
6257 - 6266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. X. Kang, J. Bell, R. L. Beard, and R. A. S. Chandraratna
Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor Mediates the Growth-Inhibitory Effects of Retinoids
Cell Growth Differ.,
August 1, 1999;
10(8):
591 - 600.
[Abstract]
[Full Text]
|
|
|
|
|
