Cancer Research Meeting Calendar Genetics and Biology of Brain Cancer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
[Cancer Research 59, 382-390, January 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Marcelli, M.
Right arrow Articles by Denner, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marcelli, M.
Right arrow Articles by Denner, L.
[Cancer Research 59, 382-390, January 15, 1999]
© 1999 American Association for Cancer Research

Experimental Therapeutics

Signaling Pathway Activated during Apoptosis of the Prostate Cancer Cell Line LNCaP: Overexpression of Caspase-7 as a New Gene Therapy Strategy for Prostate Cancer1

Marco Marcelli2, Glenn R. Cunningham, Margaret Walkup, Zening He, Lydia Sturgis, Carolina Kagan, Roberta Mannucci, Ildo Nicoletti, BaBie Teng and Larry Denner2

Departments of Medicine [M. M., G. R. C., M. W., Z. H.] and Cell Biology [M. M., G. R. C.], Veterans Administration Medical Center and Baylor College of Medicine, Houston, Texas 77030; Institute of Internal Medicine and Oncologic Sciences, Perugia University Medical School, I-06100 Perugia, Italy [R. M., I. N.]; Institute of Molecular Medicine, University of Texas, Houston Health Science Center, Houston, Texas 77030 [BB. T.]; and Department of Cell Biology, Texas Biotechnology Corporation, Houston, Texas 77030 [L. S., C. K., L. D.]

We studied the molecular mechanisms of apoptosis in the prostate cancer cell line LNCaP and whether overexpression of caspase activity could force this cell line to undergo apoptosis. The inhibitor of phosphomevalonate decarboxylase, sodium phenylacetate, and the protein kinase inhibitor staurosporine induced (a) release of cytochrome c from the mitochondria to the cytosol; (b) reduction in mitochondrial transmembrane potential ; (c) proteolytic processing of caspase-3 and -7 but not -2; (d) cleavage of the DEVD substrate and the death substrates poly(ADP-ribose) polymerase and DNA fragmentation factor; and (e) apoptosis. The panspecific inhibitor of caspase activation N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-FMK) prevented all of these events except release of mitochondrial cytochrome c into the cytosol. None of these apoptotic signaling events were elicited by staurosporine or sodium phenylacetate treatment of LNCaP-Bcl-2 cells that overexpress the oncoprotein Bcl-2. Because caspase-7 is activated in every model of apoptosis that we have characterized thus far, we wished to learn whether overexpression of this protease could directly cause apoptosis of LNCaP cells. By using a replication-defective adenovirus, overexpression of caspase-7 protein in both LNCaP and LNCaP-Bcl-2 cells was accompanied by induction of cleavage of the DEVD substrate and TUNEL. These studies have demonstrated that caspase-7 and -3 are critical mediators of apoptosis in LNCaP cells. Caspase-7 was proteolytically activated in every model of apoptosis that we have developed, and the overexpression of it induced apoptosis of LNCaP and LNCaP-Bcl-2 cells. Thus, adenoviral-mediated transfer of caspase-7 may offer a new effective approach for the treatment of prostate cancer.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
P. J. Malloy and D. Feldman
Inactivation of the Human Vitamin D Receptor by Caspase-3
Endocrinology, February 1, 2009; 150(2): 679 - 686.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
P-Y Fong, W-C Xue, H Y S Ngan, P-M Chiu, K Y K Chan, S W Tsao, and A N Y Cheung
Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study
J. Clin. Pathol., February 1, 2006; 59(2): 179 - 183.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. B. Garrison and N. Kyprianou
Doxazosin Induces Apoptosis of Benign and Malignant Prostate Cells via a Death Receptor-Mediated Pathway
Cancer Res., January 1, 2006; 66(1): 464 - 472.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
L. J. Schmidt, H. Murillo, and D. J. Tindall
Gene Expression in Prostate Cancer Cells Treated With the Dual 5 Alpha-Reductase Inhibitor Dutasteride
J Androl, November 1, 2004; 25(6): 944 - 953.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. J. Waxman and P. S. Schwartz
Harnessing Apoptosis for Improved Anticancer Gene Therapy
Cancer Res., December 15, 2003; 63(24): 8563 - 8572.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
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]

Home page
 J. Biol. Chem.Home page
T. Virolle, A. Krones-Herzig, V. Baron, G. De Gregorio, E. D. Adamson, and D. Mercola
Egr1 Promotes Growth and Survival of Prostate Cancer Cells. IDENTIFICATION OF NOVEL Egr1 TARGET GENES
J. Biol. Chem., March 28, 2003; 278(14): 11802 - 11810.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Drew, R. L. Fine, T. N. Do, G. P. Douglas, and D. P. Petrylak
The Novel Antimicrotubule Agent Cryptophycin 52 (LY355703) Induces Apoptosis via Multiple Pathways in Human Prostate Cancer Cells
Clin. Cancer Res., December 1, 2002; 8(12): 3922 - 3932.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. Agarwal, R. P. Singh, and R. Agarwal
Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release
Carcinogenesis, November 1, 2002; 23(11): 1869 - 1876.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. P. Carson, M. Behnam, J. N. Sutton, C. Du, X. Wang, D. F. Hunt, M. J. Weber, and G. Kulik
Smac Is Required for Cytochrome c-induced Apoptosis in Prostate Cancer LNCaP Cells
Cancer Res., January 1, 2002; 62(1): 18 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Liang, K. D. Nylander, C. Yan, and N. F. Schor
Role of Caspase 3-Dependent Bcl-2 Cleavage in Potentiation of Apoptosis by Bcl-2
Mol. Pharmacol., January 1, 2002; 61(1): 142 - 149.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Chatterjee, I. Schmitz, A. Krueger, K. Yeung, S. Kirchhoff, P. H. Krammer, M. E. Peter, J. H. Wyche, and P. Pantazis
Induction of Apoptosis in 9-Nitrocamptothecin-treated DU145 Human Prostate Carcinoma Cells Correlates with de Novo Synthesis of CD95 and CD95 Ligand and Down-Regulation of c-FLIPshort
Cancer Res., October 1, 2001; 61(19): 7148 - 7154.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
F. Andriani, B. Nan, J. Yu, X. Li, N. L. Weigel, M. J. McPhaul, S. Kasper, S. Kagawa, B. Fang, R. J. Matusik, et al.
Use of the Probasin Promoter ARR2PB to Express Bax in Androgen Receptor-Positive Prostate Cancer Cells
J Natl Cancer Inst, September 5, 2001; 93(17): 1314 - 1324.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Xie, X. Zhao, Y. Liu, J. Zhang, R. J. Matusik, K. M. Slawin, and D. M. Spencer
Adenovirus-mediated Tissue-targeted Expression of a Caspase-9-based Artificial Death Switch for the Treatment of Prostate Cancer
Cancer Res., September 1, 2001; 61(18): 6795 - 6804.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. M. Bruckheimer and N. Kyprianou
Dihydrotestosterone Enhances Transforming Growth Factor-{beta}-Induced Apoptosis in Hormone-Sensitive Prostate Cancer Cells
Endocrinology, June 1, 2001; 142(6): 2419 - 2426.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M.-J. Don, Y.-H. Chang, K.-K. Chen, L.-K. Ho, and Y.-P. Chau
Induction of CDK Inhibitors (p21WAF1 and p27Kip1) and Bak in the {beta}-Lapachone-Induced Apoptosis of Human Prostate Cancer Cells
Mol. Pharmacol., April 1, 2001; 59(4): 784 - 794.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
S. F. Shariat, S. Desai, W. Song, T. Khan, J. Zhao, C. Nguyen, B. A. Foster, N. Greenberg, D. M. Spencer, and K. M. Slawin
Adenovirus-mediated Transfer of Inducible Caspases: A Novel "Death Switch" Gene Therapeutic Approach to Prostate Cancer
Cancer Res., March 1, 2001; 61(6): 2562 - 2571.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
G. Kulik, J. P. Carson, T. Vomastek, K. Overman, B. D. Gooch, S. Srinivasula, E. Alnemri, G. Nunez, and M. J. Weber
Tumor Necrosis Factor {{alpha}} Induces BID Cleavage and Bypasses Antiapoptotic Signals in Prostate Cancer LNCaP Cells
Cancer Res., March 1, 2001; 61(6): 2713 - 2719.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
R. N. Winter, A. Kramer, A. Borkowski, and N. Kyprianou
Loss of Caspase-1 and Caspase-3 Protein Expression in Human Prostate Cancer
Cancer Res., February 1, 2001; 61(3): 1227 - 1232.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
V. E. Nava, O. Cuvillier, L. C. Edsall, K. Kimura, S. Milstien, E. P. Gelmann, and S. Spiegel
Sphingosine Enhances Apoptosis of Radiation-resistant Prostate Cancer Cells
Cancer Res., August 1, 2000; 60(16): 4468 - 4474.
[Abstract] [Full Text]

Home page
 JNCI J Natl Cancer InstHome page
P. Costantini, E. Jacotot, D. Decaudin, and G. Kroemer
Mitochondrion as a Novel Target of Anticancer Chemotherapy
J Natl Cancer Inst, July 5, 2000; 92(13): 1042 - 1053.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Gewies, O. W. Rokhlin, and M. B. Cohen
Cytochrome c Is Involved in Fas-mediated Apoptosis of Prostatic Carcinoma Cell Lines
Cancer Res., April 1, 2000; 60(8): 2163 - 2168.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
T. Fujii, M. L. Garcia-Bermejo, J. L. Bernabo, J. Caamano, M. Ohba, T. Kuroki, L. Li, S. H. Yuspa, and M. G. Kazanietz
Involvement of Protein Kinase C delta (PKCdelta ) in Phorbol Ester-induced Apoptosis in LNCaP Prostate Cancer Cells. LACK OF PROTEOLYTIC CLEAVAGE OF PKCdelta
J. Biol. Chem., March 10, 2000; 275(11): 7574 - 7582.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.