Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase
Autor: | Zhi-Ling Yu, Lindsey L. Morris, Huanbiao Mo, Hoda Yeganehjoo, Russell A. DeBose-Boyd, Nicolle V Fernandes, Renee Michon, Rajasekhar Katuru |
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Rok vydání: | 2013 |
Předmět: |
Male
Coenzyme A Down-Regulation Antineoplastic Agents Apoptosis Reductase Biology Article General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Cyclin D1 Geranylgeraniol Prenylation DU145 Cell Line Tumor Humans Cell Proliferation Carcinoma Prostatic Neoplasms Flow Cytometry Molecular biology Gene Expression Regulation Neoplastic Microscopy Fluorescence chemistry Biochemistry HMG-CoA reductase biology.protein Hydroxymethylglutaryl CoA Reductases Mevalonate pathway Diterpenes |
Zdroj: | Experimental Biology and Medicine. 238:1265-1274 |
ISSN: | 1535-3699 1535-3702 |
DOI: | 10.1177/1535370213492693 |
Popis: | 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. |
Databáze: | OpenAIRE |
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