Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy

Autores
Galle, Marianela Edith; Crespo, Rosana; Rodenak Kladniew, Boris Emilio; Montero Villegas, Sandra; Polo, Monica Patricia; Garcia, Margarita Maria
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Geraniol (G)—a natural compound present in the essential oils of many aromatic plants—has attracted interest for its potential antitumor effects. The molecular mechanisms of the growth inhibition and apoptosis induced by G in cancer cells, however, remain unclear. In this study, we investigated the effects of G on cell proliferation in culture in A549 cells and in vivo in those same tumor cells implanted in nude mice fed diets supplemented with 25, 50, and 75 mmol G/kg. We demonstrated that G caused a dose- and time-dependent growth inhibition of A549 cells and tumor growth in vivo along with an induction of apoptosis. Moreover, further in vivo assays indicated that G decreased the levels of 3-hydroxymethylglutarylcoenzyme-A reductase—the rate-limiting enzyme in cholesterogenesis—in a dose-dependent manner along with cholesterogenesis and cholesterolemia in addition to reducing the amount of membrane-bound Ras protein. These results showed that the doses of G used in this work, though nontoxic to animals, clearly inhibited the mevalonate pathway, which is closely linked to cell proliferation and increased apoptosis in A549 tumors, but not in normal mouse-liver cells. Accordingly, we suggest that G displays significant antitumor activity and should be a promising candidate for cancer chemotherapy.
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 ; Argentina
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 ; Argentina
Fil: Rodenak Kladniew, Boris Emilio. 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 ; Argentina
Fil: Montero Villegas, Sandra. 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 ; Argentina
Fil: Polo, Monica Patricia. 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 ; Argentina
Fil: Garcia, Margarita Maria. 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 ; Argentina
Materia
Geraniol
Apoptosis
Hmgcr
Cholesterogenesis
A549
Cell Proliferation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/32290
Acceder
id CONICETDig_1f59c098782b98d6392cde80a7c92eb0
oai_identifier_str oai:ri.conicet.gov.ar:11336/32290
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer ChemotherapyGalle, Marianela EdithCrespo, RosanaRodenak Kladniew, Boris EmilioMontero Villegas, SandraPolo, Monica PatriciaGarcia, Margarita MariaGeraniolApoptosisHmgcrCholesterogenesisA549Cell Proliferationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Geraniol (G)—a natural compound present in the essential oils of many aromatic plants—has attracted interest for its potential antitumor effects. The molecular mechanisms of the growth inhibition and apoptosis induced by G in cancer cells, however, remain unclear. In this study, we investigated the effects of G on cell proliferation in culture in A549 cells and in vivo in those same tumor cells implanted in nude mice fed diets supplemented with 25, 50, and 75 mmol G/kg. We demonstrated that G caused a dose- and time-dependent growth inhibition of A549 cells and tumor growth in vivo along with an induction of apoptosis. Moreover, further in vivo assays indicated that G decreased the levels of 3-hydroxymethylglutarylcoenzyme-A reductase—the rate-limiting enzyme in cholesterogenesis—in a dose-dependent manner along with cholesterogenesis and cholesterolemia in addition to reducing the amount of membrane-bound Ras protein. These results showed that the doses of G used in this work, though nontoxic to animals, clearly inhibited the mevalonate pathway, which is closely linked to cell proliferation and increased apoptosis in A549 tumors, but not in normal mouse-liver cells. Accordingly, we suggest that G displays significant antitumor activity and should be a promising candidate for cancer chemotherapy.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 ; ArgentinaFil: 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 ; ArgentinaFil: Rodenak Kladniew, Boris Emilio. 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 ; ArgentinaFil: Montero Villegas, Sandra. 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 ; ArgentinaFil: Polo, Monica Patricia. 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 ; ArgentinaFil: Garcia, Margarita Maria. 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 ; ArgentinaLawrence Erlbaum Assoc Inc-taylor & Francis2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32290Garcia, Margarita Maria; Polo, Monica Patricia; Montero Villegas, Sandra; Rodenak Kladniew, Boris Emilio; Crespo, Rosana; Galle, Marianela Edith; et al.; Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy; Lawrence Erlbaum Assoc Inc-taylor & Francis; Nutrition And Cancer; 66; 5; 5-2014; 888-8950163-5581CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1080/01635581.2014.916320info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.1080/01635581.2014.916320info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:22:33Zoai:ri.conicet.gov.ar:11336/32290instacron: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:34982025-09-10 13:22:33.683CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
title Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
spellingShingle Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
Galle, Marianela Edith
Geraniol
Apoptosis
Hmgcr
Cholesterogenesis
A549
Cell Proliferation
title_short Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
title_full Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
title_fullStr Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
title_full_unstemmed Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
title_sort Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy
dc.creator.none.fl_str_mv Galle, Marianela Edith
Crespo, Rosana
Rodenak Kladniew, Boris Emilio
Montero Villegas, Sandra
Polo, Monica Patricia
Garcia, Margarita Maria
author Galle, Marianela Edith
author_facet Galle, Marianela Edith
Crespo, Rosana
Rodenak Kladniew, Boris Emilio
Montero Villegas, Sandra
Polo, Monica Patricia
Garcia, Margarita Maria
author_role author
author2 Crespo, Rosana
Rodenak Kladniew, Boris Emilio
Montero Villegas, Sandra
Polo, Monica Patricia
Garcia, Margarita Maria
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Geraniol
Apoptosis
Hmgcr
Cholesterogenesis
A549
Cell Proliferation
topic Geraniol
Apoptosis
Hmgcr
Cholesterogenesis
A549
Cell Proliferation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Geraniol (G)—a natural compound present in the essential oils of many aromatic plants—has attracted interest for its potential antitumor effects. The molecular mechanisms of the growth inhibition and apoptosis induced by G in cancer cells, however, remain unclear. In this study, we investigated the effects of G on cell proliferation in culture in A549 cells and in vivo in those same tumor cells implanted in nude mice fed diets supplemented with 25, 50, and 75 mmol G/kg. We demonstrated that G caused a dose- and time-dependent growth inhibition of A549 cells and tumor growth in vivo along with an induction of apoptosis. Moreover, further in vivo assays indicated that G decreased the levels of 3-hydroxymethylglutarylcoenzyme-A reductase—the rate-limiting enzyme in cholesterogenesis—in a dose-dependent manner along with cholesterogenesis and cholesterolemia in addition to reducing the amount of membrane-bound Ras protein. These results showed that the doses of G used in this work, though nontoxic to animals, clearly inhibited the mevalonate pathway, which is closely linked to cell proliferation and increased apoptosis in A549 tumors, but not in normal mouse-liver cells. Accordingly, we suggest that G displays significant antitumor activity and should be a promising candidate for cancer chemotherapy.
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 ; Argentina
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 ; Argentina
Fil: Rodenak Kladniew, Boris Emilio. 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 ; Argentina
Fil: Montero Villegas, Sandra. 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 ; Argentina
Fil: Polo, Monica Patricia. 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 ; Argentina
Fil: Garcia, Margarita Maria. 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 ; Argentina
description Geraniol (G)—a natural compound present in the essential oils of many aromatic plants—has attracted interest for its potential antitumor effects. The molecular mechanisms of the growth inhibition and apoptosis induced by G in cancer cells, however, remain unclear. In this study, we investigated the effects of G on cell proliferation in culture in A549 cells and in vivo in those same tumor cells implanted in nude mice fed diets supplemented with 25, 50, and 75 mmol G/kg. We demonstrated that G caused a dose- and time-dependent growth inhibition of A549 cells and tumor growth in vivo along with an induction of apoptosis. Moreover, further in vivo assays indicated that G decreased the levels of 3-hydroxymethylglutarylcoenzyme-A reductase—the rate-limiting enzyme in cholesterogenesis—in a dose-dependent manner along with cholesterogenesis and cholesterolemia in addition to reducing the amount of membrane-bound Ras protein. These results showed that the doses of G used in this work, though nontoxic to animals, clearly inhibited the mevalonate pathway, which is closely linked to cell proliferation and increased apoptosis in A549 tumors, but not in normal mouse-liver cells. Accordingly, we suggest that G displays significant antitumor activity and should be a promising candidate for cancer chemotherapy.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
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/11336/32290
Garcia, Margarita Maria; Polo, Monica Patricia; Montero Villegas, Sandra; Rodenak Kladniew, Boris Emilio; Crespo, Rosana; Galle, Marianela Edith; et al.; Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy; Lawrence Erlbaum Assoc Inc-taylor & Francis; Nutrition And Cancer; 66; 5; 5-2014; 888-895
0163-5581
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32290
identifier_str_mv Garcia, Margarita Maria; Polo, Monica Patricia; Montero Villegas, Sandra; Rodenak Kladniew, Boris Emilio; Crespo, Rosana; Galle, Marianela Edith; et al.; Suppression by Geraniol of the Growth of A549 Human Lung Adenocarcinoma Cells and Inhibition of the Mevalonate Pathway in Culture and In Vivo: Potential Use in Cancer Chemotherapy; Lawrence Erlbaum Assoc Inc-taylor & Francis; Nutrition And Cancer; 66; 5; 5-2014; 888-895
0163-5581
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1080/01635581.2014.916320
info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.1080/01635581.2014.916320
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lawrence Erlbaum Assoc Inc-taylor & Francis
publisher.none.fl_str_mv Lawrence Erlbaum Assoc Inc-taylor & Francis
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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