The Winship team’s results outline a route to alternatives to celecoxib that keep its cancer-preventive properties while avoiding its risks.
Celecoxib’s risk profile has confined its use to people who have inherited cancer risk or those who have had cancer already. Its effectiveness at stopping tumour progression and recurrence is being tested in several clinical trials for people who have had lung, head and neck and other types of cancer.
Doctor Shi-Yong Sun and colleagues that celecoxib inhibits an enzyme called GSK3 (glycogen synthase kinase 3) in lung cancer cells. This causes the disappearance of a protein called c-FLIP, which usually staves off apoptosis, a form of cellular suicide.
“We have been focusing on how celecoxib induces c-FLIP degradation and apoptosis in cancer cells, independent of COX-2 inhibition,” Sun says.
Scientists think that celecoxib’s ability to inhibit COX-2 enzymes is the basis for its anti-inflammatory properties as well as its influence on heart disease. In cell culture, some chemical relatives of celecoxib have been shown to have anticancer effects without inhibiting COX-2.
The result was surprising partly because until a few years ago, scientists thought that inhibiting GSK3, while possibly helpful in diseases such as diabetes, could promote cancer. However, recent results suggest that blocking GSK3 may stop cell growth in prostate, pancreatic and colon cancers and some types of leukaemia.
Sun cautions: “We do not know whether GSK3 inhibition by celecoxib has anything to do with celecoxib’s cardiovascular risk.”
MEDICA.de; Source: Emory University