Researchers have discovered how a nonsteroidal anti-inflammatory drug (NSAID) can inhibit tumor growth, according to a study published in Cancer Cell (2010 Jun 15;17(6):560-73).
The study, led by Xiao-kun Zhang, PhD, professor at Sanford-Burnham, focused on Sulindac, an NSAID currently prescribed for the treatment of pain and fever and for the relief of arthritis symptoms. Researchers created a new version of Sulindac, called K-80003, to avoid potentially dangerous cardiovascular side effects to both decrease negative consequences and increase binding to the nuclear receptor RXRa, a protein that receives a signal and carries it into the nucleus to turn genes on or off.
“Nuclear receptors are excellent targets for drug development,” Dr. Zhang explained. “Thirteen percent of existing drugs target nuclear receptors, even though the mechanism of action is not always clear.”
Results of the study revealed that Sulindac shuts down cancer cell growth and initiates cell death by binding to RXRa. Researchers also found that Sulindac can be used to combat RxRa by switching off its pro-survival function and turning on apoptosis.
“Depending on the conditions, the same protein, such as RXRa, can either kill cancer cells or promote their growth, Dr. Zhang concluded. “The addition of K-80003 shifts that balance by blocking survival pathways and sensitizing cancer cells to triggers of apoptosis.”