INDUCTION OF THE APOPTOSIS-PROMOTING PROTEIN BAK BY PERILLYL ALCOHOL IN PANCREATIC DUCTAL ADENOCARCINOMA RELATIVE TO UNTRANSFORMED DUCTAL EPITHELIAL-CELLS

Perillyl alcohol has antitumor activity toward pancreas and other canc ers with low toxicity, Here, we have investigated the mechanism of act ion responsible for the differential sensitivity of malignant versus n on-malignant pancreatic cells to the drug. We report that the rate of apoptosis is over 6-fold higher in perillyl alcohol-treated pancreatic adenocarcinoma cells than in untreated cells, and that the effect of perillyl alcohol on pancreatic tumor cells is significantly greater th an its effect on non-malignant pancreatic ductal cells, Moreover, the perillyl alcohol-induced increase in apoptosis in ail of the pancreati c tumor cells is associated with a 2- to 8-fold increase in the expres sion of the proapoptotic protein Bah, but Bah expression is not affect ed by perillyl alcohol in non-malignant cells, Thus, the antitumor act ivity of perillyl alcohol toward pancreatic cancers may be due to pref erential stimulation of Bah-induced apoptosis in malignant versus norm al cells, Bak may, therefore, be a useful biomarker for the chemopreve ntive and therapeutic effects of perillyl alcohol.