Inhibition of type I and type II geranylgeranyl-protein transferases by the monoterpene perillyl alcohol in NIH3T3 cells

Ren, Zhibin; Elson, Charles E.; Gould, Michael N.

doi:10.1016/s0006-2952(97)00151-2

Cited by 73 publications

(62 citation statements)

References 20 publications

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“…In addition to early findings that isoprenoids may inhibit posttranslational protein prenylation (Crowell et al, 1991;Ren et al, 1997), reported effects include induction of G 0 /G 1 cell cycle arrest (Yu et al, 1995;Miquel et al, 1998;Clark et al, 2002;Elegbede et al, 2003), increased apoptosis (Haug et al, 1994;Mills et al, 1995;Reddy et al, 1997;Stayrook et al, 1997;Ariazi et al, 1999;Rioja et al, 2000;Burke et al, 2002;Clark et al, 2002;Elegbede et al, 2003;Xu et al, 2004), transient G 2 /M phase arrest (Shi and Gould, 2002;Rajesh and Howard, 2003), inhibition of cholesterol biosynthesis (Ren and Gould, 1994;Peffley and Gayen, 2003), inhibition of angiogenesis (Loutrari et al, 2004), and increased sensitization to radiation and anticancer drugs (Samaila et al, 2004).…”

mentioning

confidence: 88%

Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21^Cip1and p27^Kip1in Human Pancreatic Adenocarcinoma Cells

Wiseman¹,

Werner²,

Crowell³

2006

J Pharmacol Exp Ther

137

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mentioning

confidence: 88%

Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21^Cip1and p27^Kip1in Human Pancreatic Adenocarcinoma Cells

Wiseman¹,

Werner²,

Crowell³

2006

J Pharmacol Exp Ther

137

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“…The mechanisms by which these isoprenoids induce these effects are not yet fully understood. Isoprenoids have been reported to inhibit posttranslational protein prenylation (19) whereas other studies have shown that FOH is a potent inhibitor of the CDP-choline pathway (5,20,21). Other effects include inhibition of phospholipase D (22), inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) activity (6), generation of reactive oxygen species (ROS; refs.…”

Section: Introductionmentioning

confidence: 99%

Farnesol-Induced Apoptosis in Human Lung Carcinoma Cells Is Coupled to the Endoplasmic Reticulum Stress Response

Joo¹,

Liao²,

et al. 2007

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Farnesol (FOH) and other isoprenoid alcohols induce apoptosis in various carcinoma cells and inhibit tumorigenesis in several in vivo models. However, the mechanisms by which they mediate their effects are not yet fully understood. In this study, we show that FOH is an effective inducer of apoptosis in several lung carcinoma cells, including H460. This induction is associated with activation of several caspases and cleavage of poly(ADP-ribose) polymerase (PARP). To obtain insight into the mechanism involved in FOH-induced apoptosis, we compared the gene expression profiles of FOH-treated and control H460 cells by microarray analysis. This analysis revealed that many genes implicated in endoplasmic reticulum (ER) stress signaling, including ATF3, DDIT3, HERPUD1, HSPA5, XBP1, PDIA4, and PHLDA1, were highly up-regulated within 4 h of FOH treatment, suggesting that FOH-induced apoptosis involves an ER stress response. This was supported by observations showing that treatment with FOH induces splicing of XBP1 mRNA and phosphorylation of eIF2A. FOH induces activation of several mitogen-activated protein kinase (MAPK) pathways, including p38, MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK, and c-jun NH 2 -terminal kinase (JNK). Inhibition of MEK1/2 by U0126 inhibited the induction of ER stress response genes. In addition, knockdown of the MEK1/2 and JNK1/2 expression by short interfering RNA (siRNA) effectively inhibited the cleavage of caspase-3 and PARP and apoptosis induced by FOH. However, only MEK1/2 siRNAs inhibited the induction of ER stress-related genes, XBP1 mRNA splicing, and eIF2A phosphorylation. Our results show that FOH-induced apoptosis is coupled to ER stress and that activation of MEK1/2 is an early upstream event in the FOH-induced ER stress signaling cascade. [Cancer Res 2007;67(16):7929-36]

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“…Although metabolites of the monoterpene limonene are able to inhibit one or more protein:prenyl transferase, none of these specifically inhibits Rab GGTase. For example, perillyl alcohol inhibits Rab GGTase, but also GGTase I in cell-free lysates and intact 3T3 cells (6), whereas other monoterpenes, such as perillic acid, inhibit FTase and GGTase I only (7).…”

mentioning

confidence: 99%

Identification of a Novel Phosphonocarboxylate Inhibitor of Rab Geranylgeranyl Transferase That Specifically Prevents Rab Prenylation in Osteoclasts and Macrophages

Coxon

Helfrich²,

Larijani

et al. 2001

Journal of Biological Chemistry

158

162

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Nitrogen-containing bisphosphonate drugs inhibit bone resorption by inhibiting FPP synthase and thereby preventing the synthesis of isoprenoid lipids required for protein prenylation in bone-resorbing osteoclasts. NE10790 is a phosphonocarboxylate analogue of the potent bisphosphonate risedronate and is a weak antiresorptive agent. Although NE10790 was a poor inhibitor of FPP synthase, it did inhibit prenylation in J774 macrophages and osteoclasts, but only of proteins of molecular mass ϳ22-26 kDa, the prenylation of which was not affected by peptidomimetic inhibitors of either farnesyl transferase (FTI-277) or geranylgeranyl transferase I (GGTI-298). These 22-26-kDa proteins were shown to be geranylgeranylated by labelling J774 cells with [ 3 H]geranylgeraniol. Furthermore, NE10790 inhibited incorporation of [ 14 C]mevalonic acid into Rab6, but not into H-Ras or Rap1, proteins that are modified by FTase and GGTase I, respectively. These data demonstrate that NE10790 selectively prevents Rab prenylation in intact cells. In accord, NE10790 inhibited the activity of recombinant Rab GGTase in vitro, but did not affect the activity of recombinant FTase or GGTase I. NE10790 therefore appears to be the first specific inhibitor of Rab GGTase to be identified. In contrast to risedronate, NE10790 inhibited bone resorption in vitro without markedly affecting osteoclast number or the F-actin "ring" structure in polarized osteoclasts. However, NE10790 did alter osteoclast morphology, causing the formation of large intracellular vacuoles and protrusion of the basolateral membrane into large, "domed" structures that lacked microvilli. The anti-resorptive activity of NE10790 is thus likely due to disruption of Rabdependent intracellular membrane trafficking in osteoclasts.

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Inhibition of type I and type II geranylgeranyl-protein transferases by the monoterpene perillyl alcohol in NIH3T3 cells

Cited by 73 publications

References 20 publications

Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21^Cip1and p27^Kip1in Human Pancreatic Adenocarcinoma Cells

Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21^Cip1and p27^Kip1in Human Pancreatic Adenocarcinoma Cells

Farnesol-Induced Apoptosis in Human Lung Carcinoma Cells Is Coupled to the Endoplasmic Reticulum Stress Response

Identification of a Novel Phosphonocarboxylate Inhibitor of Rab Geranylgeranyl Transferase That Specifically Prevents Rab Prenylation in Osteoclasts and Macrophages

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Inhibition of type I and type II geranylgeranyl-protein transferases by the monoterpene perillyl alcohol in NIH3T3 cells

Cited by 73 publications

References 20 publications

Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21Cip1and p27Kip1in Human Pancreatic Adenocarcinoma Cells

Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21Cip1and p27Kip1in Human Pancreatic Adenocarcinoma Cells

Farnesol-Induced Apoptosis in Human Lung Carcinoma Cells Is Coupled to the Endoplasmic Reticulum Stress Response

Identification of a Novel Phosphonocarboxylate Inhibitor of Rab Geranylgeranyl Transferase That Specifically Prevents Rab Prenylation in Osteoclasts and Macrophages

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Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21^Cip1and p27^Kip1in Human Pancreatic Adenocarcinoma Cells

Cell Cycle Arrest by the Isoprenoids Perillyl Alcohol, Geraniol, and Farnesol Is Mediated by p21^Cip1and p27^Kip1in Human Pancreatic Adenocarcinoma Cells