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Artículo

Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in two Hep-G2 cell-proliferation–linked pathways

Crespo, RosanaIcon ; Montero Villegas, SandraIcon ; Abba, Martín CarlosIcon ; Garcia de Bravo, Margarita; Polo, Monica PatriciaIcon
Fecha de publicación: 05/2013
Editorial: National Research Council Canada-NRC Research Press
Revista: Biochemistry and Cell Biology
ISSN: 0829-8211
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitumor activity against several cell lines. We investigated the effects of geraniol on lipid metabolic pathways involved in Hep-G2 cell proliferation and found that geraniol inhibits the mevalonate pathway, phosphatidylcholine biosynthesis, cell growth, and cell cycle progression (with an arrest occurring at the G0/G1 interphase) and increases apoptosis. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting step in cholesterol synthesis, was inhibited at the transcriptional and posttranscriptional levels, as assessed by real-time RT–PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. That geraniol decreased cholesterogenesis but increased the incorporation of [14C]acetate into other nonsaponifiable metabolites indicated the existence of a second control point between squalene and cholesterol involved in redirecting the flow of cholesterol-derived carbon toward other metabolites of the mevalonate pathway. That exogenous mevalonate failed to restore growth in geraniol-inhibited cells suggests that, in addition to the inhibition of HMGCR, other dose-dependent actions exist through which geraniol can impact the mevalonate pathway and consequently inhibit cell proliferation. These results suggest that geraniol, a nontoxic compound found in many fruits and herbs, exhibits notable potential as a natural agent for combatting cancer and (or) cardiovascular diseases
Palabras clave: Geraniol , Hmgr , Phosphatidylcholine , Cell Proliferation , Hep-G2
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/24832
DOI: http://dx.doi.org/10.1139/bcb-2012-0076
URL: http://www.nrcresearchpress.com/doi/abs/10.1139/bcb-2012-0076
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Articulos(INIBIOLP)
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Citación
Crespo, Rosana; Montero Villegas, Sandra; Abba, Martín Carlos; Garcia de Bravo, Margarita; Polo, Monica Patricia; Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in two Hep-G2 cell-proliferation–linked pathways; National Research Council Canada-NRC Research Press; Biochemistry and Cell Biology; 91; 3; 5-2013; 131-139
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