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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Chemical References |
- Antineoplastic Agents
- BAK1 protein, human
- Membrane Proteins
- Monoterpenes
- Terpenes
- bcl-2 Homologous Antagonist-Killer Protein
- perillyl alcohol
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Topics |
- Adenocarcinoma
(metabolism, pathology)
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
- Cell Division
(drug effects)
- Cricetinae
- Dose-Response Relationship, Drug
- Epithelium
(metabolism, pathology)
- Humans
- Membrane Proteins
(metabolism)
- Monoterpenes
- Pancreatic Ducts
- Pancreatic Neoplasms
(metabolism, pathology)
- Terpenes
(pharmacology)
- bcl-2 Homologous Antagonist-Killer Protein
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