TY - JOUR
T1 - Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase
AU - Fernandes, Nicolle V.
AU - Yeganehjoo, Hoda
AU - Katuru, Rajasekhar
AU - DeBose-Boyd, Russell A.
AU - Morris, Lindsey L.
AU - Michon, Renee
AU - Yu, Zhiling
AU - Mo, Huanbiao
N1 - Funding Information:
This work was partially supported by Texas Department of Agriculture Food and Fiber Research Program, Texas Woman’s University Research Enhancement Program, Summer Stipend Award and Human Nutrition Research Fund, American River Nutrition, Inc., National Institute of Health (GM090216), and the Howard Hughes Medical Institutes.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - apoptosis
KW - cell cycle
KW - Geranylgeraniol
KW - HMG CoA reductase
KW - mevalonate
KW - prostate carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84887174107&partnerID=8YFLogxK
U2 - 10.1177/1535370213492693
DO - 10.1177/1535370213492693
M3 - Journal article
C2 - 24006306
AN - SCOPUS:84887174107
SN - 1535-3702
VL - 238
SP - 1265
EP - 1274
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 11
ER -
