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, Zhiling Yu, Huanbiao Mo*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

16 Citations (Scopus)


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
Pages (from-to)1265-1274
Number of pages10
JournalExperimental Biology and Medicine
Issue number11
Publication statusPublished - Nov 2013

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)

User-Defined Keywords

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


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