|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 47, 45408-45419, November 22, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Retinoids have great promise in the area of
cancer therapy and chemoprevention. Although some tumor cells are
sensitive to the growth inhibitory effect of
all-trans-retinoic acid (ATRA), many ovarian tumor cells
are not. 6-((1-Admantyl)-4-hydroxyphenyl)-2-naphthalenecarboxylic acid
(CD437) is a conformationally restricted synthetic retinoid that
induces growth arrest and apoptosis in both ATRA-sensitive and
ATRA-resistant ovarian tumor cell lines. To better understand the
mechanism by which CD437 induces apoptosis in ovarian tumor cell lines,
we prepared a cell line, CA-CD437R, from the ATRA-sensitive ovarian
cell line, CA-OV-3, which was resistant to CD437. We found that the
CD437-resistant cell line was also resistant to the induction of
apoptosis by tumor necrosis factor-
Elucidation of Molecular Events Mediating Induction of Apoptosis
by Synthetic Retinoids Using a CD437-resistant Ovarian Carcinoma Cell
Line*
§,
, and**
Department of Microbiology & Immunology and
¶ Department of Biochemistry, Fels Institute for Cancer
Research and Molecular Biology, Temple University School of Medicine,
Philadelphia, Pennsylvania 19140
but not resistant to the induction of apoptosis by another synthetic retinoid, fenretinide N-(4-hydroxyphenyl)retinamide. We also show that this cell
line remains ATRA-sensitive and exhibits no deficiencies in RAR
function. Analysis of this CD437-resistant cell line suggests that the
pathway for induction of apoptosis by CD437 is similar to the pathway utilized by tumor necrosis factor- and different from the pathway induced by the synthetic retinoid, fenretinide
N-(4-hydroxyphenyl)retinamide. The CA-CD437R cell line is a
valuable tool, permitting us to further elucidate the molecular events
that mediate apoptosis induced by CD437 and other synthetic
retinoids. Results of experiments utilizing this cell line suggest that
the alteration responsible for resistance of CA-CD437R cells to CD437
induced event maps after the activation of p38 and TR3 expression,
prior to mitochondrial depolarization, subsequent release of cytochrome
c and activation of caspase-9 and caspase-3.
*
This work was supported in part by National Institutes of
Health Grants CA 64945 and DE 13139 (to K. J. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Hormi-Carver, L. A. Feagins, S. J. Spechler, and R. F. Souza All trans-retinoic acid induces apoptosis via p38 and caspase pathways in metaplastic Barrett's cells Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G18 - G27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Kaiser, M. Korner, A. Kappeler, and S. Aebi Retinoid receptors in ovarian cancer: expression and prognosis Ann. Onc., September 1, 2005; 16(9): 1477 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Cao, W. Liu, F. Lin, H. Li, S. K. Kolluri, B. Lin, Y.-h. Han, M. I. Dawson, and X.-k. Zhang Retinoid X Receptor Regulates Nur77/Thyroid Hormone Receptor 3-Dependent Apoptosis by Modulating Its Nuclear Export and Mitochondrial Targeting Mol. Cell. Biol., November 15, 2004; 24(22): 9705 - 9725. [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. K. Kolluri, N. Bruey-Sedano, X. Cao, B. Lin, F. Lin, Y.-H. Han, M. I. Dawson, and X.-k. Zhang Mitogenic Effect of Orphan Receptor TR3 and Its Regulation by MEKK1 in Lung Cancer Cells Mol. Cell. Biol., December 1, 2003; 23(23): 8651 - 8667. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |