INDUCTION OF THE APOPTOSIS-PROMOTING PROTEIN BAK BY PERILLYL ALCOHOL IN PANCREATIC DUCTAL ADENOCARCINOMA RELATIVE TO UNTRANSFORMED DUCTAL EPITHELIAL-CELLS
Kr. Stayrook et al., INDUCTION OF THE APOPTOSIS-PROMOTING PROTEIN BAK BY PERILLYL ALCOHOL IN PANCREATIC DUCTAL ADENOCARCINOMA RELATIVE TO UNTRANSFORMED DUCTAL EPITHELIAL-CELLS, Carcinogenesis, 18(8), 1997, pp. 1655-1658
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.