| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print October 2, 2001
Pharmacology, Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160
Corresponding Author: marcelo{at}spirit.gcrc.upenn.edu
Phorbol esters, the archetypical PKC activators, induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. In this study we evaluate the effect of a novel class of PKC ligands, the DAG-lactones, as inducers of apoptosis in LNCaP cells. These unique ligands were designed using novel pharmacophore- and receptor-guided approaches to achieve highly potent DAG surrogates. Two of these compounds, HK434 and HK654, induced apoptosis in LNCaP cells with much higher potency than oleoyl-acetyl-glycerol (OAG) or phorbol 12, 13-dibutyrate (PDBu). Moreover, different PKC isozymes were found to mediate the apoptotic effect of phorbol 12-myristate 13-acetate (PMA) and HK654 in LNCaP cells. Using PKC inhibitors and dominant-negative PKC isoforms, we found that both PKC
J. Biol. Chem, 10.1074/jbc.M107639200
Submitted on August 9, 2001
Revised on September 18, 2001
Accepted on October 2, 2001
DAG-lactones, a new class of PKC agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKC
and PKC
mediated the apoptotic effect of PMA whereas only PKC was involved in the effect of the DAG-lactone. The PKC selectivity of HK654 in LNCaP cells contrasts with similar potencies in vitro for binding and activation of PKC and PKC. Consistent with the differences in isoform dependence in intact cells, PMA and HK654 show marked differences in their abilities to translocate PKC isozymes. Both PMA and HK654 induce a marked redistribution of PKC to the plasma membrane. On the other hand, unlike PMA, HK654 translocates PKC predominantly to the nuclear membrane. Thus, DAG-lactones have a unique profile of activation of PKC isozymes for inducing apoptosis in LNCaP cells, and represent the first example of a selective activator of a classical PKC (cPKC) in cellular models. An attractive hypothesis is that selective activation of PKC isozymes by pharmacological agents in cells can be achieved by differential intracellular targeting of each PKC.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Paone, D. Starace, R. Galli, F. Padula, P. De Cesaris, A. Filippini, E. Ziparo, and A. Riccioli Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-{alpha}-dependent mechanism Carcinogenesis, July 1, 2008; 29(7): 1334 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, F. Deng, S. V. Singh, and Q. J. Wang Protein Kinase D3 (PKD3) Contributes to Prostate Cancer Cell Growth and Survival Through a PKC{varepsilon}/PKD3 Pathway Downstream of Akt and ERK 1/2 Cancer Res., May 15, 2008; 68(10): 3844 - 3853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Choi, G. Czifra, N. Kedei, N. E. Lewin, J. Lazar, Y. Pu, V. E. Marquez, and P. M. Blumberg Characterization of the Interaction of Phorbol Esters with the C1 Domain of MRCK (Myotonic Dystrophy Kinase-related Cdc42 Binding Kinase) {alpha}/{beta} J. Biol. Chem., April 18, 2008; 283(16): 10543 - 10549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Oliva, M. C. Caino, A. M. Senderowicz, and M. G. Kazanietz S-Phase-specific Activation of PKC{alpha} Induces Senescence in Non-small Cell Lung Cancer Cells J. Biol. Chem., February 29, 2008; 283(9): 5466 - 5476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Gavrielides, A. M. Gonzalez-Guerrico, N. A. Riobo, and M. G. Kazanietz Androgens Regulate Protein Kinase C{delta} Transcription and Modulate Its Apoptotic Function in Prostate Cancer Cells Cancer Res., December 15, 2006; 66(24): 11792 - 11801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Walker, P. Castagnino, B. M. Chung, M. G. Kazanietz, and R. K. Assoian Post-transcriptional Destabilization of p21cip1 by Protein Kinase C in Fibroblasts J. Biol. Chem., December 15, 2006; 281(50): 38127 - 38132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jiang, H.-J. Lee, G.-x. Li, J. Guo, B. Malewicz, Y. Zhao, E.-O. Lee, H.-J. Lee, J.-H. Lee, M.-S. Kim, et al. Potent Antiandrogen and Androgen Receptor Activities of an Angelica gigas-Containing Herbal Formulation: Identification of Decursin as a Novel and Active Compound with Implications for Prevention and Treatment of Prostate Cancer Cancer Res., January 1, 2006; 66(1): 453 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Santiago-Walker, A. J. Fikaris, G. D. Kao, E. J. Brown, M. G. Kazanietz, and J. L. Meinkoth Protein Kinase C {delta} Stimulates Apoptosis by Initiating G1 Phase Cell Cycle Progression and S Phase Arrest J. Biol. Chem., September 16, 2005; 280(37): 32107 - 32114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Sandra, M. Degli Esposti, K. Ndebele, P. Gona, D. Knight, M. Rosenquist, and R. Khosravi-Far Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Alters Mitochondrial Membrane Lipids Cancer Res., September 15, 2005; 65(18): 8286 - 8297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hara, Y. Saito, T. Hirai, K. Nakamura, K. Nakao, M. Katsuki, and K. Chida Deficiency of Protein Kinase C{alpha} in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis Cancer Res., August 15, 2005; 65(16): 7356 - 7362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shim and T. E. Eling Protein Kinase C-dependent Regulation of NAG-1/Placental Bone Morphogenic Protein/MIC-1 Expression in LNCaP Prostate Carcinoma Cells J. Biol. Chem., May 13, 2005; 280(19): 18636 - 18642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yin, N. Bennani-Baiti, and C. T. Powell Phorbol Ester-induced Apoptosis of C4-2 Cells Requires Both a Unique and a Redundant Protein Kinase C Signaling Pathway J. Biol. Chem., February 18, 2005; 280(7): 5533 - 5541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M. Sakaguchi, M. Miyazaki, H. Sonegawa, M. Kashiwagi, M. Ohba, T. Kuroki, M. Namba, and N.-h. Huh PKC{alpha} mediates TGF{beta}-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11 J. Cell Biol., March 29, 2004; 164(7): 979 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Comalada, J. Xaus, A. F. Valledor, C. Lopez-Lopez, D. J. Pennington, and A. Celada PKC{epsilon} is involved in JNK activation that mediates LPS-induced TNF-{alpha}, which induces apoptosis in macrophages Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1235 - C1245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Hamer, S. Bocklandt, L. McHugh, T.-W. Chun, P. M. Blumberg, D. M. Sigano, and V. E. Marquez Rational Design of Drugs That Induce Human Immunodeficiency Virus Replication J. Virol., October 1, 2003; 77(19): 10227 - 10236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tanaka, M. V. Gavrielides, Y. Mitsuuchi, T. Fujii, and M. G. Kazanietz Protein Kinase C Promotes Apoptosis in LNCaP Prostate Cancer Cells through Activation of p38 MAPK and Inhibition of the Akt Survival Pathway J. Biol. Chem., September 5, 2003; 278(36): 33753 - 33762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cataisson, E. Joseloff, R. Murillas, A. Wang, C. Atwell, S. Torgerson, M. Gerdes, J. Subleski, J.-L. Gao, P. M. Murphy, et al. Activation of Cutaneous Protein Kinase C{alpha} Induces Keratinocyte Apoptosis and Intraepidermal Inflammation by Independent Signaling Pathways J. Immunol., September 1, 2003; 171(5): 2703 - 2713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, M. I. Gonzalez, J. L. Meinkoth, J. Field, M. G. Kazanietz, and G. I. Tennekoon Lysophosphatidic Acid Promotes Survival and Differentiation of Rat Schwann Cells J. Biol. Chem., March 7, 2003; 278(11): 9585 - 9591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Kazanietz Novel "Nonkinase" Phorbol Ester Receptors: The C1 Domain Connection Mol. Pharmacol., April 1, 2002; 61(4): 759 - 767. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
