( xib and sulindac sulfide's anticancer a...)Combining NSAIDs With Chemotherapy May Improve Cancer Therapy,Health

xib and sulindac sulfide's anticancer activity was mediated through cell cycle inhibition and induction of apoptosis (cell suicide) and was not related to the drugs' anti-inflammatory properties.

In a second study, published in the April 15 issue of Cancer Research, the UI team shows how celecoxib exerts its anticancer effect by altering protein expression in ways that disrupt the cell cycle and lead to cell death.

Cells go through three phases before they divide: G1 phase, where the cell grows and makes protein; S phase, where the cell makes DNA and replicates its chromosomes; and G2 phase, where the cell prepares for division. The cell cycle also contains several well-defined checkpoints where the growing cell stops and "decides" that things are ready to move on to the next stage.

The UI research found that celecoxib alters the expression of G1 checkpoint proteins and significantly decreases the activity of a protein called E2F1. This activity is required for cells to move through the cell cycle and also is crucial for S phase activities like DNA repair. Celecoxib's inhibition of E2F1 activity may be a reason for the drug's observed S phase-specific toxicity.

Trask notes that the study results have identified a set of biomarkers that appear to predict how effective a drug is at killing cancer cells, which should facilitate screening of other compounds that might have anticancer effects similar to celecoxib, but could be used in lower, perhaps safer, doses.


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