JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on August 4, 2005; DOI: 10.1124/jpet.105.088567

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.105.088567v1
315/2/526    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guo, M.
Right arrow Articles by Scicli, A. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guo, M.
Right arrow Articles by Scicli, A. G.


Received for publication May 17, 2005.
Revised July 8, 2005.
Accepted for publication August 2, 2005.

Human U251 Glioma Cell Proliferation is Suppressed by HET0016, a Selective Inhibitor of CYP4A

Meng Guo 1*, Richard J Roman 2, John R Falck 3, Paul A Edwards 1, A. Guillermo Scicli 1

1 Henry Ford Hospital 2 Medical College of Wisconsin 3 University of Texas Southwestern Medical Center

* Address correspondence to: E-mail: mengguo{at}hotmail.com

Abstract

We have previously reported that HET0016 [N-hydroxy-N'-(4-butyl-2 methylphenyl) formamidine], a selective inhibitor of CYP4A and thus 20-HETE synthesis, inhibits endothelial cell proliferation, and decreases angiogenesis induced by human glioma cell U251. A stable 20-HETE agonist, 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (WIT003; 1 µM) increased U251 cell proliferation from 3.9 to 4.8 folds from T0. We examined the effects of HET0016 on the growth of U251. HET0016 inhibited U251 basal cell proliferation in a dose-dependent manner. 10 µM HET0016 suppressed 56% of U251 proliferation, and significantly increased the proportions of the cells arrested in the G0/G1 phase of the cell cycle. Exposure to HET0016 (as early as 4hr) reduced protein tyrosine and p42/p44 MAPK phosphorylation. Further, HET0016 significantly inhibited the U251 proliferation and phosphorylation of both the EGF receptor and p42/p44 MAPK induced by EGF. CYP4A mRNA and proteins were both present in U251. This suggests that HET0016 inhibited U251 proliferation by inhibiting 20-HETE synthesis. However, U251 did not synthesize 20-HETE in the presence of arachidonic acid. This implies that HET0016 suppresses U251 proliferation by mechanisms, not yet clear but are likely other than the inhibition of 20-HETE synthesis. We concluded that HET0016 may be the prototype of novel compounds that suppress human glioma cell proliferation.


Key words: 20-HETE, CYP4A inhibitors, Cytochrome P450 4A, U251 glioma cells, cell proliferation, glioblastoma


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
A. M. Guo, J. Sheng, G. M. Scicli, A. S. Arbab, N. L. Lehman, P. A. Edwards, J. R. Falck, R. J. Roman, and A. G. Scicli
Expression of CYP4A1 in U251 Human Glioma Cell Induces Hyperproliferative Phenotype in Vitro and Rapidly Growing Tumors in Vivo
J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 10 - 19.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
F. Park, W. E. Sweeney, G. Jia, R. J. Roman, and E. D. Avner
20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease
J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1929 - 1939.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. M. Guo, A. S. Arbab, J. R. Falck, P. Chen, P. A. Edwards, R. J. Roman, and A. G. Scicli
Activation of Vascular Endothelial Growth Factor through Reactive Oxygen Species Mediates 20-Hydroxyeicosatetraenoic Acid-Induced Endothelial Cell Proliferation
J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 18 - 27.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Guo, R. J. Roman, J. D. Fenstermacher, S. L. Brown, J. R. Falck, A. S. Arbab, P. A. Edwards, and A. G. Scicli
9L Gliosarcoma Cell Proliferation and Tumor Growth in Rats Are Suppressed by N-Hydroxy-N'-(4-butyl-2-methylphenol) Formamidine (HET0016), a Selective Inhibitor of CYP4A
J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 97 - 108.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.