Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase

Nicolle V. Fernandes, Hoda Yeganehjoo, Rajasekhar Katuru, Russell A. DeBose-Boyd, Lindsey L. Morris, Renee Michon, Zhi Ling Yu, Huanbiao Mo

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1265-1274
Number of pages10
JournalExperimental Biology and Medicine
Volume238
Issue number11
DOIs
StatePublished - Nov 2013

Fingerprint

Coenzyme A
Prostate
Oxidoreductases
Cells
Carcinoma
Down-Regulation
Dolichol
Lamins
Prenylation
Glycosylation
Mevalonic Acid
Acridine Orange
Ethidium
Growth Factor Receptors
Diterpenes
Fluorescence microscopy
Cyclin D1
Chemoprevention
G1 Phase
Sterols

Keywords

  • apoptosis
  • cell cycle
  • Geranylgeraniol
  • HMG CoA reductase
  • mevalonate
  • prostate carcinoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase. / Fernandes, Nicolle V.; Yeganehjoo, Hoda; Katuru, Rajasekhar; DeBose-Boyd, Russell A.; Morris, Lindsey L.; Michon, Renee; Yu, Zhi Ling; Mo, Huanbiao.

In: Experimental Biology and Medicine, Vol. 238, No. 11, 11.2013, p. 1265-1274.

Research output: Contribution to journalArticle

Fernandes, Nicolle V. ; Yeganehjoo, Hoda ; Katuru, Rajasekhar ; DeBose-Boyd, Russell A. ; Morris, Lindsey L. ; Michon, Renee ; Yu, Zhi Ling ; Mo, Huanbiao. / Geranylgeraniol suppresses the viability of human DU145 prostate carcinoma cells and the level of HMG CoA reductase. In: Experimental Biology and Medicine. 2013 ; Vol. 238, No. 11. pp. 1265-1274.
@article{d27367e56e8c472487d318def0ab81b6,
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.",
keywords = "apoptosis, cell cycle, Geranylgeraniol, HMG CoA reductase, mevalonate, prostate carcinoma",
author = "Fernandes, {Nicolle V.} and Hoda Yeganehjoo and Rajasekhar Katuru and DeBose-Boyd, {Russell A.} and Morris, {Lindsey L.} and Renee Michon and Yu, {Zhi Ling} and Huanbiao Mo",
year = "2013",
month = "11",
doi = "10.1177/1535370213492693",
language = "English (US)",
volume = "238",
pages = "1265--1274",
journal = "Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "11",

}

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, Zhi Ling

AU - Mo, Huanbiao

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

UR - http://www.scopus.com/inward/citedby.url?scp=84887174107&partnerID=8YFLogxK

U2 - 10.1177/1535370213492693

DO - 10.1177/1535370213492693

M3 - Article

VL - 238

SP - 1265

EP - 1274

JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

SN - 1535-3702

IS - 11

ER -