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

11 Scopus citations

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 1 2013

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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