title: Induction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells.
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.
authors.affiliation: Department of Biology, Indiana University-Purdue University at Indianapolis, 46202, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Stayrook
authors.forename: J H
authors.initials: JH
authors.lastname: McKinzie
authors.forename: Y D
authors.initials: YD
authors.lastname: Burke
authors.forename: Y A
authors.initials: YA
authors.lastname: Burke
authors.forename: P L
authors.initials: PL
authors.lastname: Crowell
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D039821:Monoterpenes; D010183:Pancreatic Ducts; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D013729:Terpenes / Q000494:pharmacology*; D050998:bcl-2 Homologous Antagonist-Killer Protein
chemical_list: D000970:Antineoplastic Agents; C494772:BAK1 protein, human; D008565:Membrane Proteins; D039821:Monoterpenes; D013729:Terpenes; D050998:bcl-2 Homologous Antagonist-Killer Protein; C032208:perillyl alcohol