STIMULATION OF APOPTOSIS BY SULINDAC AND PIROXICAM

1. Sulindac, yl-1-(p-methylsulphinylbenzylidene)indene-3-acetic acid, inhibits growth of colon polyps and cancers. This effect has been attr ibuted to inhibition of prostaglandin synthesis but more recent observ ations indicate that, in vitro, cells that do not have cyclo-oxygenase nor RNA for synthesis of such enzymes are affected by sulindac. There fore the presumptive effect is probably not correct. 2. It has also be en found that sulindac stimulates apoptosis. It is herein postulated t hat in tumour cells such effects may be due to interaction of the anio nic form of the drug with protons in the intermembrane space of mitoch ondria to disrupt the potential across the inner mitochondrial membran e and thereby initiate apoptosis. Normal cells are not affected.