title: Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase.
abstract: The rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates for the prenylation of nuclear lamins and Ras and dolichol-mediated glycosylation of growth factor receptors. The diterpene geranylgeraniol downregulates the level of HMG CoA reductase and suppresses the growth of human liver, lung, ovary, pancreas, colon, stomach, and blood tumors. We evaluated the growth-suppressive activity of geranylgeraniol in human prostate carcinoma cells. Geranylgeraniol induced dose-dependent suppression of the viability of human DU145 prostate carcinoma cells (IC50=80±18 µmol/L, n=5) following 72-h incubations in 96-well plates. Cell cycle was arrested at the G1 phase with a concomitant decrease in cyclin D1 protein. Geranylgeraniol-induced apoptosis was detected by flow cytometric analysis, fluorescence microscopy following acridine orange and ethidium bromide dual staining, and caspase-3 activation. Geranylgeraniol-induced viability suppression was accompanied by concentration-dependent decrease in the level of HMG CoA reductase protein. As a nonsterol molecule that downregulates HMG CoA reductase in the presence of sterols, geranylgeraniol may have potential in the chemoprevention and/or therapy of human prostate cancer.
authors.affiliation: Department of Nutrition and Food Sciences, Texas Woman's University, Denton, TX 76204, USA.
authors.forename: Nicolle V
authors.initials: NV
authors.lastname: Fernandes
authors.forename: Hoda
authors.initials: H
authors.lastname: Yeganehjoo
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Katuru
authors.forename: Russell A
authors.initials: RA
authors.lastname: DeBose-Boyd
authors.forename: Lindsey L
authors.initials: LL
authors.lastname: Morris
authors.forename: Renee
authors.initials: R
authors.lastname: Michon
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
authors.forename: Huanbiao
authors.initials: H
authors.lastname: Mo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C017338:geranylgeraniol; D006903:Hydroxymethylglutaryl CoA Reductases
keywords: Geranylgeraniol; HMG CoA reductase; apoptosis; cell cycle; mevalonate; prostate carcinoma