Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR

Autores
Crespo, Rosana; Galle, Marianela Edith; Bravo, Margarita G. de; Polo, Mónica P.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation with selectivity against tumor cells. Isoprenoids are also potent suppressors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme catalyzing the main rate-limiting step of the mevalonate pathway and cholesterol synthesis in mammalian cells. HMGCR inhibition decreases the elevated cholesterol levels widely required by rapidly growing cancer cells, inhibits the prenylation of certain growth-regulatory proteins that play a key role in controlling cell proliferation, and induces apoptosis. Geraniol, an acyclic isoprenoid monoterpene, occurring in the essential oils of several aromatic plants, is thought to represent a new class of chemotherapeutic agent. In order to evaluate the antiproliferative property of geraniol in vitro and in vivo, and to understand the mechanisms by which this monoterpene inhibits cell growth, we studied its effects on human- lung epithelial (A549) and human-hepatoma cell lines (HepG2) as well as on A549 implanted in nude mice fed with 50-75 mmol.GOH/kg diet for 21 days. Viability and proliferation of cells incubated with 200 -600 µM geraniol were determined by trypan-blue?dye-exclusion cell and by the MTT assay. Apoptosis was determined by TUNEL assay and caspase-3 activity. HMGCR expression was analyzed by real-time RT-PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. Lipid synthesis was assessed by incorporation of [14C]acetate. Our results showed that 200 -600 µM geraniol inhibits cell proliferation in both cell lines. HMGCR-mRNA expression was significantly increased in liver cells but HMGCR-protein levels and enzymatic activity, along with cholesterol synthesis, became significantly decreased. These results showed that geraniol down-regulates the enzyme by a posttranscriptional mechanism. In vivo assays geraniol significantly reduced tumor growth and significantly enhanced apoptosis of tumor cells. Treated host-mice also showed a decreased in HMGGR-protein levels and cholesterogenesis. The relevance of this work resides in the finding that geraniol both decreases HMGCR levels and inhibits tumor cell proliferation in vitro and in vivo suggesting that geraniol has a great potential as a natural drug against cancer.
Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Galle, Marianela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Bravo, Margarita G. de. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Polo, Mónica P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Materia
Geraniol
Cell-Proliferation
Posttranscriptional-Regulation
Hmgcr
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/102760
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCRCrespo, RosanaGalle, Marianela EdithBravo, Margarita G. dePolo, Mónica P.GeraniolCell-ProliferationPosttranscriptional-RegulationHmgcrhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation with selectivity against tumor cells. Isoprenoids are also potent suppressors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme catalyzing the main rate-limiting step of the mevalonate pathway and cholesterol synthesis in mammalian cells. HMGCR inhibition decreases the elevated cholesterol levels widely required by rapidly growing cancer cells, inhibits the prenylation of certain growth-regulatory proteins that play a key role in controlling cell proliferation, and induces apoptosis. Geraniol, an acyclic isoprenoid monoterpene, occurring in the essential oils of several aromatic plants, is thought to represent a new class of chemotherapeutic agent. In order to evaluate the antiproliferative property of geraniol in vitro and in vivo, and to understand the mechanisms by which this monoterpene inhibits cell growth, we studied its effects on human- lung epithelial (A549) and human-hepatoma cell lines (HepG2) as well as on A549 implanted in nude mice fed with 50-75 mmol.GOH/kg diet for 21 days. Viability and proliferation of cells incubated with 200 -600 µM geraniol were determined by trypan-blue?dye-exclusion cell and by the MTT assay. Apoptosis was determined by TUNEL assay and caspase-3 activity. HMGCR expression was analyzed by real-time RT-PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. Lipid synthesis was assessed by incorporation of [14C]acetate. Our results showed that 200 -600 µM geraniol inhibits cell proliferation in both cell lines. HMGCR-mRNA expression was significantly increased in liver cells but HMGCR-protein levels and enzymatic activity, along with cholesterol synthesis, became significantly decreased. These results showed that geraniol down-regulates the enzyme by a posttranscriptional mechanism. In vivo assays geraniol significantly reduced tumor growth and significantly enhanced apoptosis of tumor cells. Treated host-mice also showed a decreased in HMGGR-protein levels and cholesterogenesis. The relevance of this work resides in the finding that geraniol both decreases HMGCR levels and inhibits tumor cell proliferation in vitro and in vivo suggesting that geraniol has a great potential as a natural drug against cancer.Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Galle, Marianela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Bravo, Margarita G. de. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Polo, Mónica P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaPalacky Univ2012-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/102760Crespo, Rosana; Galle, Marianela Edith; Bravo, Margarita G. de; Polo, Mónica P.; Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR; Palacky Univ; Biomedical Papers-olomouc; 156; Supl. 1; 7-2012; 95-951213-8118CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://biomed.papers.upol.cz/incpdfs/pri-990000-0200_10_026.pdfinfo:eu-repo/semantics/altIdentifier/url/https://biomed.papers.upol.cz/artkey/pri-990000-0200_VOLUME_156_Supplement_1.phpinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:57Zoai:ri.conicet.gov.ar:11336/102760instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:05:58.042CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
title Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
spellingShingle Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
Crespo, Rosana
Geraniol
Cell-Proliferation
Posttranscriptional-Regulation
Hmgcr
title_short Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
title_full Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
title_fullStr Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
title_full_unstemmed Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
title_sort Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR
dc.creator.none.fl_str_mv Crespo, Rosana
Galle, Marianela Edith
Bravo, Margarita G. de
Polo, Mónica P.
author Crespo, Rosana
author_facet Crespo, Rosana
Galle, Marianela Edith
Bravo, Margarita G. de
Polo, Mónica P.
author_role author
author2 Galle, Marianela Edith
Bravo, Margarita G. de
Polo, Mónica P.
author2_role author
author
author
dc.subject.none.fl_str_mv Geraniol
Cell-Proliferation
Posttranscriptional-Regulation
Hmgcr
topic Geraniol
Cell-Proliferation
Posttranscriptional-Regulation
Hmgcr
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation with selectivity against tumor cells. Isoprenoids are also potent suppressors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme catalyzing the main rate-limiting step of the mevalonate pathway and cholesterol synthesis in mammalian cells. HMGCR inhibition decreases the elevated cholesterol levels widely required by rapidly growing cancer cells, inhibits the prenylation of certain growth-regulatory proteins that play a key role in controlling cell proliferation, and induces apoptosis. Geraniol, an acyclic isoprenoid monoterpene, occurring in the essential oils of several aromatic plants, is thought to represent a new class of chemotherapeutic agent. In order to evaluate the antiproliferative property of geraniol in vitro and in vivo, and to understand the mechanisms by which this monoterpene inhibits cell growth, we studied its effects on human- lung epithelial (A549) and human-hepatoma cell lines (HepG2) as well as on A549 implanted in nude mice fed with 50-75 mmol.GOH/kg diet for 21 days. Viability and proliferation of cells incubated with 200 -600 µM geraniol were determined by trypan-blue?dye-exclusion cell and by the MTT assay. Apoptosis was determined by TUNEL assay and caspase-3 activity. HMGCR expression was analyzed by real-time RT-PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. Lipid synthesis was assessed by incorporation of [14C]acetate. Our results showed that 200 -600 µM geraniol inhibits cell proliferation in both cell lines. HMGCR-mRNA expression was significantly increased in liver cells but HMGCR-protein levels and enzymatic activity, along with cholesterol synthesis, became significantly decreased. These results showed that geraniol down-regulates the enzyme by a posttranscriptional mechanism. In vivo assays geraniol significantly reduced tumor growth and significantly enhanced apoptosis of tumor cells. Treated host-mice also showed a decreased in HMGGR-protein levels and cholesterogenesis. The relevance of this work resides in the finding that geraniol both decreases HMGCR levels and inhibits tumor cell proliferation in vitro and in vivo suggesting that geraniol has a great potential as a natural drug against cancer.
Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Galle, Marianela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Bravo, Margarita G. de. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Polo, Mónica P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
description Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation with selectivity against tumor cells. Isoprenoids are also potent suppressors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme catalyzing the main rate-limiting step of the mevalonate pathway and cholesterol synthesis in mammalian cells. HMGCR inhibition decreases the elevated cholesterol levels widely required by rapidly growing cancer cells, inhibits the prenylation of certain growth-regulatory proteins that play a key role in controlling cell proliferation, and induces apoptosis. Geraniol, an acyclic isoprenoid monoterpene, occurring in the essential oils of several aromatic plants, is thought to represent a new class of chemotherapeutic agent. In order to evaluate the antiproliferative property of geraniol in vitro and in vivo, and to understand the mechanisms by which this monoterpene inhibits cell growth, we studied its effects on human- lung epithelial (A549) and human-hepatoma cell lines (HepG2) as well as on A549 implanted in nude mice fed with 50-75 mmol.GOH/kg diet for 21 days. Viability and proliferation of cells incubated with 200 -600 µM geraniol were determined by trypan-blue?dye-exclusion cell and by the MTT assay. Apoptosis was determined by TUNEL assay and caspase-3 activity. HMGCR expression was analyzed by real-time RT-PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. Lipid synthesis was assessed by incorporation of [14C]acetate. Our results showed that 200 -600 µM geraniol inhibits cell proliferation in both cell lines. HMGCR-mRNA expression was significantly increased in liver cells but HMGCR-protein levels and enzymatic activity, along with cholesterol synthesis, became significantly decreased. These results showed that geraniol down-regulates the enzyme by a posttranscriptional mechanism. In vivo assays geraniol significantly reduced tumor growth and significantly enhanced apoptosis of tumor cells. Treated host-mice also showed a decreased in HMGGR-protein levels and cholesterogenesis. The relevance of this work resides in the finding that geraniol both decreases HMGCR levels and inhibits tumor cell proliferation in vitro and in vivo suggesting that geraniol has a great potential as a natural drug against cancer.
publishDate 2012
dc.date.none.fl_str_mv 2012-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/102760
Crespo, Rosana; Galle, Marianela Edith; Bravo, Margarita G. de; Polo, Mónica P.; Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR; Palacky Univ; Biomedical Papers-olomouc; 156; Supl. 1; 7-2012; 95-95
1213-8118
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102760
identifier_str_mv Crespo, Rosana; Galle, Marianela Edith; Bravo, Margarita G. de; Polo, Mónica P.; Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR; Palacky Univ; Biomedical Papers-olomouc; 156; Supl. 1; 7-2012; 95-95
1213-8118
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://biomed.papers.upol.cz/incpdfs/pri-990000-0200_10_026.pdf
info:eu-repo/semantics/altIdentifier/url/https://biomed.papers.upol.cz/artkey/pri-990000-0200_VOLUME_156_Supplement_1.php
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Palacky Univ
publisher.none.fl_str_mv Palacky Univ
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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