INVESTIGADORES
ABBA Martin Carlos
artículos
Título:
Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways
Autor/es:
CRESPO R; MONTERO VILLEGAS S; ABBA MC; DE BRAVO MG; POLO MP
Revista:
BIOCHEMISTRY AND CELL BIOLOGY
Editorial:
NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS
Referencias:
Lugar: Otawa; Año: 2013 vol. 91 p. 131 - 139
ISSN:
0829-8211
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 RTPCR, 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.