Effects of the isoprenoids perillyl alcohol and farnesol on apoptosis biomarkers in pancreatic cancer chemoprevention.
Perillyl alcohol, farnesol and geraniol have chemotherapeutic activity toward pancreatic and other cancers. Perillyl alcohol induces apoptosis and increases expression of the proapoptotic protein Bak in cultured pancreatic tumor cells. We tested the hypothesis that farnesol and geraniol would have similar effects. After 48 hours of treatment with farnesol geraniol or perillyl alcohol, human BxPC3 pancreatic cancer cells exhibited a 3 to 10-fold increase in apoptosis and higher Bak expression than the controls. We then tested the hypotheses that perillyl alcohol and farnesol would have chemopreventive activity toward pancreatic cancer and would increase Bak expression and apoptosis in vivo. Hamster pancreatic cancer was initiated at time 0 with N-nitrosobis(2-oxopropyl)amine. Animals were fed control, 2% (w/w) perillyl alcohol, or 1% (w/w) farnesol diets from weeks 5-42. Pancreatic carcinoma incidence was decreased by perillyl alcohol and farnesol. Hyperplastic pancreatic ductal neoplasms from perillyl alcohol and farnesol-treated animals had higher Bak protein expression (p < 0.05), and somewhat higher apoptotic rates, diminished expression of the antiapoptotic protein BCL-XL, and lower rates of DNA synthesis than the controls.
Burke
Yvette D
YD
Department of Biology, Indiana University-Purdue University Indianapolis, 723 West Michigan St., Room SL3 10, Indianapolis, IN 46202-5132, USA.
Ayoubi
A Siar
AS
Werner
Sean R
SR
McFarland
Bryan C
BC
Heilman
Douglas K
DK
Ruggeri
Bruce A
BA
Crowell
Pamela L
PL
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002273:Carcinogens; D021441:Carcinoma, Pancreatic Ductal / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006224:Cricetinae; D005204:Farnesol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008647:Mesocricetus; D039821:Monoterpenes / Q000494:pharmacology*; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D050998:bcl-2 Homologous Antagonist-Killer Protein
D016588:Anticarcinogenic Agents; C494772:BAK1 protein, human; D014408:Biomarkers, Tumor; D002273:Carcinogens; D008565:Membrane Proteins; D039821:Monoterpenes; D009602:Nitrosamines; D050998:bcl-2 Homologous Antagonist-Killer Protein; C032208:perillyl alcohol; D005204:Farnesol; C013622:nitrosobis(2-oxopropyl)amine