Skip Navigation

This Article
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (159)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hennings, H.
Right arrow Articles by Yuspa, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hennings, H.
Right arrow Articles by Yuspa, S. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1987 Oxford University Press

research-article

Bryostatin 1, an activator of protein kinase C, inhibits tumor promotion by phorbol esters in SENCAR mouse skin

Henry Hennings, Peter M. Blumberg, George R. Pettit, Cherry L. Herald 1, Robert Shores 2 and Stuart H. Yuspa

Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute Bethesda, MD 20892, USA
1Cancer Research Institute and Department of Chemistry, Arizona State University Tempe, AZ 85287, USA
2Microbiological Associates Inc. Bethesda, MD 20816, USA

Bryostatin 1, like the phorbol esters, activates protein kinase C. However, bryostatin 1 induces only some of the effects in cultured cells which result from phorbol ester treatment, whereas it blocks other responses to the phorbol esters. In mouse keratinocytes in particular, bryostatin 1 induces ornithine decarboxylase, a marker of proliferation, but blocks induction of markers of differentiation. Because of the postulated role of induction of differentiation in tumor promotion, we have now examined bryostatin 1 as a tumor promoter and as an inhibitor of phorbol ester tumor promotion in the initiation—promotion model of skin carcinogenesis. After initiation with 7,12-dimethylbenz[a]anthracene, weekly topical treatments of the backs of mice with 1 µg(1.1 nmol) bryostatin 1 induced epidermal hyperplasia and inflammation, although not to the extent seen after treatment with the promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment with bryostatin 15 min before each TPA exposure reduced the phorbol ester-induced hyperplasia. Bryostatin 1 was ineffective as a complete tumor promoter and displayed very weak activity as a second stage promoter upon treatment of initiated mice for 30 weeks. Combined exposure of mice to bryostatin 1 and TPA resulted in a substantial inhibition of promotion by TPA. Our in vivo results extend earlier in vitro findings that bryostatin 1 acts as a partial inhibitor of protein kinease C function.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
M.-K. Sun, J. Hongpaisan, T. J. Nelson, and D. L. Alkon
Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains
PNAS, September 9, 2008; 105(36): 13620 - 13625.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. F. El-Rayes, S. Gadgeel, A. F. Shields, S. Manza, P. Lorusso, and P. A. Philip
Phase I Study of Bryostatin 1 and Gemcitabine
Clin. Cancer Res., December 1, 2006; 12(23): 7059 - 7062.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Li, W. Wojciechowski, C. Dell'Agnola, N. E. Lopez, and I. Espinoza-Delgado
IFN-{gamma} and T-bet Expression in Human Dendritic Cells from Normal Donors and Cancer Patients Is Controlled through Mechanisms Involving ERK-1/2-Dependent and IL-12-Independent Pathways
J. Immunol., September 15, 2006; 177(6): 3554 - 3563.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. S. Garcia, R. E. Curiel, J. M. Mwatibo, S. Pestka, H. Li, and I. Espinoza-Delgado
The Antineoplastic Agent Bryostatin-1 Differentially Regulates IFN-{gamma} Receptor Subunits in Monocytic Cells: Transcriptional and Posttranscriptional Control of IFN-{gamma}R2
J. Immunol., August 15, 2006; 177(4): 2707 - 2716.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. C. Tuthill, C. E. Oki, and P. S. Lorenzo
Differential effects of bryostatin 1 and 12-O-tetradecanoylphorbol-13-acetate on the regulation and activation of RasGRP1 in mouse epidermal keratinocytes.
Mol. Cancer Ther., March 1, 2006; 5(3): 602 - 610.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W. Wojciechowski, H. Li, S. Marshall, C. Dell'Agnola, and I. Espinoza-Delgado
Enhanced Expression of CD20 in Human Tumor B Cells Is Controlled through ERK-Dependent Mechanisms
J. Immunol., June 15, 2005; 174(12): 7859 - 7868.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Do, V. L. Hegde, P. S. Nagarkatti, and M. Nagarkatti
Bryostatin-1 Enhances the Maturation and Antigen-Presenting Ability of Murine and Human Dendritic Cells
Cancer Res., September 15, 2004; 64(18): 6756 - 6765.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Etcheberrigaray, M. Tan, I. Dewachter, C. Kuiperi, I. Van der Auwera, S. Wera, L. Qiao, B. Bank, T. J. Nelson, A. P. Kozikowski, et al.
Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice
PNAS, July 27, 2004; 101(30): 11141 - 11146.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Kedei, D. J. Lundberg, A. Toth, P. Welburn, S. H. Garfield, and P. M. Blumberg
Characterization of the Interaction of Ingenol 3-Angelate with Protein Kinase C
Cancer Res., May 1, 2004; 64(9): 3243 - 3255.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
D. N. JACKSON and D. A. FOSTER
The enigmatic protein kinase C{delta}: complex roles in cell proliferation and survival
FASEB J, April 1, 2004; 18(6): 627 - 636.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Wang, Z. Wang, P. Dent, and S. Grant
Induction of tumor necrosis factor by bryostatin 1 is involved in synergistic interactions with paclitaxel in human myeloid leukemia cells
Blood, May 1, 2003; 101(9): 3648 - 3657.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
L. Cartee, S. C. Maggio, R. Smith, H. M. Sankala, P. Dent, and S. Grant
Protein Kinase C-dependent Activation of the Tumor Necrosis Factor Receptor-mediated Extrinsic Cell Death Pathway Underlies Enhanced Apoptosis in Human Myeloid Leukemia Cells Exposed to Bryostatin 1 and Flavopiridol
Mol. Cancer Ther., January 1, 2003; 2(1): 83 - 93.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
N. E. Caporaso
Why Have We Failed to Find the Low Penetrance Genetic Constituents of Common Cancers?
Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1544 - 1549.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. A. Knauf, L. S. Ward, Y. E. Nikiforov, M. Nikiforova, E. Puxeddu, M. Medvedovic, T. Liron, D. Mochly-Rosen, and J. A. Fagin
Isozyme-Specific Abnormalities of PKC in Thyroid Cancer: Evidence for Post-Transcriptional Changes in PKC Epsilon
J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2150 - 2159.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
A. B. da Rocha, D.R.A. Mans, A. Regner, and G. Schwartsmann
Targeting Protein Kinase C: New Therapeutic Opportunities Against High-Grade Malignant Gliomas?
Oncologist, February 1, 2002; 7(1): 17 - 33.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. E. Curiel, C. S. Garcia, L. Farooq, M. F. Aguero, and I. Espinoza-Delgado
Bryostatin-1 and IL-2 Synergize to Induce IFN-{gamma} Expression in Human Peripheral Blood T Cells: Implications for Cancer Immunotherapy
J. Immunol., November 1, 2001; 167(9): 4828 - 4837.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. C. Song, C. M. Hanson, V. Tsai, O. C. Farokhzad, M. Lotz, and J. B. Matthews
Regulation of epithelial transport and barrier function by distinct protein kinase C isoforms
Am J Physiol Cell Physiol, August 1, 2001; 281(2): C649 - C661.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. J. Slater, F. J. Taddeo, A. Mazurek, B. A. Stagliano, S. K. Milano, M. B. Kelly, C. Ho, and C. D. Stubbs
Inhibition of Membrane Lipid-independent Protein Kinase Calpha Activity by Phorbol Esters, Diacylglycerols, and Bryostatin-1
J. Biol. Chem., September 4, 1998; 273(36): 23160 - 23168.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. S. Lorenzo, K. Bogi, P. Acs, G. R. Pettit, and P. M. Blumberg
The Catalytic Domain of Protein Kinase Cdelta Confers Protection from Down-regulation Induced by Bryostatin 1
J. Biol. Chem., December 26, 1997; 272(52): 33338 - 33343.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. C. Bosco, S. Rottschafer, L. S. Taylor, J. R. Ortaldo, D. L. Longo, and I. Espinoza-Delgado
The Antineoplastic Agent Bryostatin-1 Induces Proinflammatory Cytokine Production in Human Monocytes: Synergy With Interleukin-2 and Modulation of Interleukin-2Rgamma Chain Expression
Blood, May 1, 1997; 89(9): 3402 - 3411.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
H.-W. Lee, L. Smith, G. R. Pettit, and J. B. Smith
Bryostatin 1 and Phorbol Ester Down-Modulate Protein Kinase C-alpha and -epsilon via the Ubiquitin/Proteasome Pathway in Human Fibroblasts
Mol. Pharmacol., March 1, 1997; 51(3): 439 - 447.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-W. Lee, L. Smith, G. R. Pettit, A. Vinitsky, and J. B. Smith
Ubiquitination of Protein Kinase C-alpha and Degradation by the Proteasome
J. Biol. Chem., August 30, 1996; 271(35): 20973 - 20976.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
U. Gundimeda, Z.-H. Chen, and R. Gopalakrishna
Tamoxifen Modulates Protein Kinase C via Oxidative Stress in Estrogen Receptor-negative Breast Cancer Cells
J. Biol. Chem., June 7, 1996; 271(23): 13504 - 13514.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. J. Slater, C. Ho, M. B. Kelly, J. D. Larkin, F. J. Taddeo, M. D. Yeager, and C. D. Stubbs
Protein Kinase Calpha Contains Two Activator Binding Sites That Bind Phorbol Esters and Diacylglycerols with Opposite Affinities
J. Biol. Chem., March 1, 1996; 271(9): 4627 - 4631.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Gomez-Angelats, C. D. Bortner, and J. A. Cidlowski
Protein Kinase C (PKC) Inhibits Fas Receptor-induced Apoptosis through Modulation of the Loss of K+ and Cell Shrinkage. A ROLE FOR PKC UPSTREAM OF CASPASES
J. Biol. Chem., June 23, 2000; 275(26): 19609 - 19619.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.