ction of cGMP-dependent protein kinase G (PKG). This rise in PKG activity causes beta-catenin to be degraded in neoplastic cells, thus triggering cell death by apoptosis through well-studied mechanisms. In addition, SAANDs that are better inhibitors of PDE5 and PDE2 than exisulind also show parallel increases in ability to induce apoptosis and inhibit growth of the cancer cells.

"Exisulind and other SAANDs appear to act at an early point in the biochemical pathway that controls apoptosis and survival of cancer cells," said W. Joseph Thompson, Ph.D., vice president of research at Cell Pathways and lead author of the publication. "Our initial data indicates that increased PDE5 expression, and in some cases PDE2, occurs in precancerous and cancerous lesions. This over-expression appears to keep cGMP low in cells that have abnormal proliferation or apoptosis rates. The data indicate that by inhibiting cGMP PDE activity in cancer cells, a sustained rise in cGMP occurs, triggering cell death through protein kinase G. In normal cells, the cGMP pathway does not appear to be important in the regulation of apoptosis. Exisulind and other SAANDs restore the ability of abnormal cells to die by inhibiting that cGMP PDE activity."

New Insights in the Biology of Cancer

Cyclic nucleotide PDEs consist of 11 gene families, each having one or more different members or "isoforms." Each family of PDEs is characterized by their ability to bind and degrade cyclic AMP (cAMP) and/or cGMP, but differs in their immunological, physical and kinetic properties. Only a limited number of PDE isoforms are expressed and used by any single type of cell or tissue to regulate cGMP or cAMP levels. Pharmaceutical developers have been studying these enzymes as potential drug targets to modulated cyclic nucleotide levels in diseases where their levels are important, such as asthma and heart disease. Until now, PDE inhibitors have not been developed as anti-cancer agents. Mo
'"/>

Contact: Joan Kureczka
JKureczka@aol.com
415-821-2413
Kureczka/Martin Associates
4-Jul-2000

Page: 1 2 3
Related biology news :

1. NIH awards $18.2m to The Burnham Institute to develop Center on Proteolytic Pathways
2. Pathways of emotion from cortex to peripheral organs
3. Cell Pathways CP461 demonstrates multiple anti-cancer activities
4. Cell Pathways Reports Extension Study Results Showing Ability Of FGN-1 To Prevent Formation Of Precancerous Colon Polyps
5. Pitt Researchers Find Way To Block Cellular Growth Pathways And Inhibit Tumor Growth
6. Discovery Of Genetic Pathways May Provide New Ways To Combat Candida Infections
7. DNA lends scientists a hand, revealing new chemical reactions
8. Conference at UH opens doors for new scientists, engineers
9. Wisconsin scientists develop quick botox test
10. UCI scientists successfully target key HIV protein; breakthrough may lead to new drug therapies
11. Alaska scientists find Arctic tundra yields surprising carbon loss