Cancer
Celecoxib reduces levels of cyclin D1 in Prostate Cancer
By American Association for Cancer Research
Mar 2, 2005, 17:40

Celecoxib, a selective COX-2 inhibitor with promising anti-cancer properties, has now been found to attack prostate cancer cells in a second way that differs from Vioxx (rofecoxib), another anti-inflammatory drug that also inhibits COX-2.

"It is well established that COX-2 is a significant and rational target for anti-cancer therapy," said Andrew Dannenberg, M.D., director of cancer prevention at the Weill Medical College of Cornell University and senior author of the paper.

"These studies suggest that celecoxib exerts a second mode of action independent of its known anti-inflammatory mechanism that imposes further restrictions on the proliferation of prostate cancer cells. The results provide potentially important insights into our understanding of the overall anti-tumor activity of selective COX-2 inhibitors."

Dannenberg and a team of investigators discovered this new mechanism by applying celecoxib to prostate cancer cells that failed to express COX-2. Here, the scientists observed that the celecoxib-treated cancer cells did not replicate as rapidly as untreated cells. After further analysis, they found the drug worked by suppressing amounts of cyclin D1, a protein that's essential if cells are to grow, divide and spread.

The scientists also attempted to replicate the experiment with Vioxx substituting for celecoxib. In this case, the prostate cancer cells continued to flourish.

"These results support the notion of a unique action by celecoxib that is independent of COX-2, and that's different from Vioxx," said Dannenberg.

"These beneficial effects were observed at concentrations of celecoxib that occur in humans," added Dannenberg. "This increases the likelihood that our findings are clinically relevant."

Dannenberg and his colleagues then demonstrated that celecoxib worked in animals that served as hosts for human prostate tumors. In this animal model, celecoxib not only was shown to reduce proliferation of cancer cells, but also reduced the growth of blood vessels at the tumor sites. As a result, tumor mass and blood vessel density in the treated animals was about half that observed in the untreated animals.





All rights reserved by www.rxpgnews.com