Induction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells.
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| Abstract |
Perillyl alcohol has antitumor activity toward pancreas and other cancers with low toxicity. Here, we have investigated the mechanism of action responsible for the differential sensitivity of malignant versus non-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 than its effect on non-malignant pancreatic ductal cells. Moreover, the perillyl alcohol-induced increase in apoptosis in all of the pancreatic tumor cells is associated with a 2- to 8-fold increase in the expression of the proapoptotic protein Bak, but Bak expression is not affected by perillyl alcohol in non-malignant cells. Thus, the antitumor activity of perillyl alcohol toward pancreatic cancers may be due to preferential stimulation of Bak-induced apoptosis in malignant versus normal cells. Bak may, therefore, be a useful biomarker for the chemopreventive and therapeutic effects of perillyl alcohol.
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| Authors | K R Stayrook, J H McKinzie, Y D Burke, Y A Burke, P L Crowell |
| Journal | Carcinogenesis (Carcinogenesis) Vol. 18 Issue 8 Pg. 1655-8 (Aug 1997) ISSN: 0143-3334 [Print] England |
| PMID | 9276644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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