CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

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 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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Parmer, T. G.
Right arrow Articles by Hait, W. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Parmer, T. G.
Right arrow Articles by Hait, W. N.

Cell Growth & Differentiation, Vol 8, Issue 3 327-334, Copyright © 1997 by American Association of Cancer Research


ARTICLES

Effects of rottlerin, an inhibitor of calmodulin-dependent protein kinase III, on cellular proliferation, viability, and cell cycle distribution in malignant glioma cells

TG Parmer, MD Ward and WN Hait
Department of Pharmacology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway 08854-5638, USA.

Calmodulin-dependent protein kinases phosphorylate certain substrates that have been implicated in regulating cellular proliferation. For example, upon mitogenic stimulation, there is a rapid activation of calmodulin-dependent protein kinase III (CaM kinase III), which leads to the phosphorylation of elongation factor 2. Recently, our laboratory demonstrated that the activity of CaM kinase III is increased in glioma cells following exposure to mitogens and is diminished or absent in nonproliferating glial tissue. Rottlerin, a 5,7-dihydroxy-2,2-dimethyl-6-(2,4,6-trihydroxy-3-methyl-5-acetylbenzy l)-8-cinnamoyl-1,2-chromene isolated from the pericarps of Mallotus phillippinensis, has been shown to be an effective CaM kinase III inhibitor. Therefore, we evaluated the effects of rottlerin on the growth and viability of glioblastoma cell lines. Rottlerin decreased growth and induced cytotoxicity in rat (C6) and two human gliomas (T98G and U138MG) at concentrations that inhibited the activity of CaM kinase III in vitro and in vivo. Far less demonstrable effects were observed on other Ca2++/CaM-sensitive kinases. Incubation of glial cells with rottlerin produced a block at the G1-S interface and the appearance of a population of cells with a <2N complement of DNA. In addition, rottlerin induced changes in cellular morphology such as cell shrinkage, accumulation of cytoplasmic vacuoles, and packaging of cellular components within membranes. These data suggest that CaM kinase III may be an important link between the activation of CaM-dependent signaling, proliferation, and viability in malignant cells, and that inhibition of CaM kinase III may represent an interesting pharmacological target in malignant gliomas.


This article has been cited by other articles:


Home page
J Biol ChemHome page
M. R. Lopez-Huertas, E. Mateos, G. Diaz-Gil, F. Gomez-Esquer, M. Sanchez del Cojo, J. Alcami, and M. Coiras
Protein Kinase C{theta} Is a Specific Target for Inhibition of the HIV Type 1 Replication in CD4+ T Lymphocytes
J. Biol. Chem., August 5, 2011; 286(31): 27363 - 27377.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
P. Geraldes and G. L. King
Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications
Circ. Res., April 30, 2010; 106(8): 1319 - 1331.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
J. H. Chen, M. Riazy, E. M. Smith, C. G. Proud, U. P. Steinbrecher, and V. Duronio
Oxidized LDL-Mediated Macrophage Survival Involves Elongation Factor-2 Kinase
Arterioscler Thromb Vasc Biol, January 1, 2009; 29(1): 92 - 98.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
N. Sud, S. Wedgwood, and S. M. Black
Protein kinase C{delta} regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation
Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L582 - L591.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
L. Q. Hong-Brown, C. R. Brown, D. S. Huber, and C. H. Lang
Alcohol Regulates Eukaryotic Elongation Factor 2 Phosphorylation via an AMP-activated Protein Kinase-dependent Mechanism in C2C12 Skeletal Myocytes
J. Biol. Chem., February 9, 2007; 282(6): 3702 - 3712.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
B.-H. Choi, E.-M. Hur, J.-H. Lee, D.-J. Jun, and K.-T. Kim
Protein kinase C{delta}-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death
J. Cell Sci., April 1, 2006; 119(7): 1329 - 1340.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
H. Wu, J.-M. Yang, S. Jin, H. Zhang, and W. N. Hait
Elongation Factor-2 Kinase Regulates Autophagy in Human Glioblastoma Cells
Cancer Res., March 15, 2006; 66(6): 3015 - 3023.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
S. Arora, J.-M. Yang, and W. N. Hait
Identification of the Ubiquitin-Proteasome Pathway in the Regulation of the Stability of Eukaryotic Elongation Factor-2 Kinase
Cancer Res., May 1, 2005; 65(9): 3806 - 3810.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
T. B. Deb, C. M. Coticchia, and R. B. Dickson
Calmodulin-mediated Activation of Akt Regulates Survival of c-Myc-overexpressing Mouse Mammary Carcinoma Cells
J. Biol. Chem., September 10, 2004; 279(37): 38903 - 38911.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
S. Arora, J.-M. Yang, R. Utsumi, T. Okamoto, T. Kitayama, and W. N. Hait
P-Glycoprotein Mediates Resistance to Histidine Kinase Inhibitors
Mol. Pharmacol., September 1, 2004; 66(3): 460 - 467.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
S. Arora, J.-M. Yang, T. G. Kinzy, R. Utsumi, T. Okamoto, T. Kitayama, P. A. Ortiz, and W. N. Hait
Identification and Characterization of an Inhibitor of Eukaryotic Elongation Factor 2 Kinase against Human Cancer Cell Lines
Cancer Res., October 15, 2003; 63(20): 6894 - 6899.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. Yang, J.-M. Yang, M. Iannone, W. J. Shih, Y. Lin, and W. N. Hait
Disruption of the EF-2 Kinase/Hsp90 Protein Complex: A Possible Mechanism to Inhibit Glioblastoma by Geldanamycin
Cancer Res., May 1, 2001; 61(10): 4010 - 4016.
[Abstract] [Full Text]


Home page
J Biol ChemHome page
J. Pongracz, P. Webb, K. Wang, E. Deacon, O. J. Lunn, and J. M. Lord
Spontaneous Neutrophil Apoptosis Involves Caspase 3-mediated Activation of Protein Kinase C-{delta}
J. Biol. Chem., December 24, 1999; 274(52): 37329 - 37334.
[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 Cell Growth & Differentiation
Copyright © 1997 by the American Association of Cancer Research.