Perillyl alcohol inhibits the expression and function of the androgen receptor in human prostate cancer cells.
Perillyl alcohol is a hydroxylated monocyclic monoterpene. In animal study, monoterpene has shown to have an anti-tumor effect. The aim of this study is to evaluate whether POH plays an important role in the development and progression of prostate cancer (pCa). We treated LNCaP cells with different concentrations of perillyl alcohol (POH). First of all, we performed cell proliferation assay and prostate-specific antigen (PSA) and human glandular kallikrein (hK2) quantification assays. LNCaP cells were treated with or without POH for Western blot analysis of androgen receptor (AR) and c-Jun. Finally, we performed transient transfection assay by transfecting LNCaP cells-which were treated with or without POH-with pGL-3 luciferase vector containing PSA promoter and AR promoter. We observed inhibition of the expression and function of the AR by POH, through inhibition of androgen-induced cell growth and androgen-stimulated secretion of prostate-specific antigen and hK2, in human pCa cell line LNCaP. In addition, we demonstrated, for the first time, that POH inhibits the transcription activities of the AR gene promoter by over-expression of c-Jun protein. These novel properties of POH strongly suggest that POH could be highly useful for intervention of pCa.
Chung
Byung Ha
BH
Department of Urology and the Urological Science Institute, College of Medicine, Yonsei University, Yongdong P.O. Box 1217, Seoul, Korea. chung646@yumc.yonsei.ac.kr
Lee
Hye-young
HY
Lee
Jae Seok
JS
Young
Charles Y F
CY
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020840:Tissue Kallikreins / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D039821:Monoterpenes; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; C032208:perillyl alcohol; D009277:Nandrolone; C100075:mibolerone; D008156:Luciferases; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen