Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 ISI Web of Science
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 (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Alves, F.
Right arrow Articles by Tietze, L. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alves, F.
Right arrow Articles by Tietze, L. F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Glycobiology, 2002, Vol. 12, No. 8 517-522
© 2002 Oxford University Press

Inhibition of EGF-mediated receptor activity and cell proliferation by HK1-ceramide, a stable analog of the ganglioside GM3-lactone

Frauke Alves1,2, Ulrich Borchers3, Holger Keim3, Rocco Fortte3, Jens Olschimke3, Wolfgang F. Vogel4, Hartmut Halfter5 and Lutz F. Tietze3

2 Department of Hematology and Oncology, Georg-August-University, Robert-Koch-Str. 40, 37075 Göttingen, Germany; 3 Department of Organic Chemistry, Georg-August-University, Tammannstr. 2, 37077 Göttingen, Germany; 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada; and 5 Clinic of Neurology, Westf. Wilhelms-University Münster, Albert-Schweitzer-Str. 33, 48129 Münster, Germany

Gangliosides have been described as modulators of growth factor receptor activity and subsequent cellular function. Due to the lower-pH environment found in tumor cells, ganglosides are thought to be formed (at least to some extent) into their lactone forms. The aim of the study was to analyze the mode of action of the lactone of the ganglioside GM3 on epidermal growth factor (EGF) signaling in human ovarial epidermoid carcinoma A431 cells and cell growth in human oral epidermoid carcinoma KB cells by applying the GM3 lactone analog HK1-ceramide 2, which is stable under hydrolytic conditions. Specific inhibition of EGF-dependent receptor tyrosine phosphorylation was observed by HK1-ceramide 2 at 25 µM, whereas GM3 showed a comparable inhibition at eightfold higher concentrations. In cells exposed to low pH, where GM3 is thought to form its lactone to a higher extent, addition of GM3 showed no further inhibitory effect on EGF-dependent receptor phosphorylation. Similarly to GM3, HK1-ceramide 2 does not affect binding of 125I-EGF to the cell surface receptor. EGF-dependent growth of KB cells was also found to be inhibited by HK1-ceramide 2 at much lower concentrations compared to GM3. In conclusion, our results indicate that the GM3 lactone analog HK1-ceramide 2 is a specific inhibitor of EGF receptor function and is more potent in reducing EGF-dependent tyrosine phosphorylation of the receptor in A431 cells and in inhibiting EGF-dependent growth of KB cells compared to GM3.

1 To whom correspondence should be addressed; E-mail: falves@gwdg.de


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




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.