Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells

Autores
Colombero Rivas, Cecilia Edith; Papademetrio, Daniela Laura; Sacca, Paula Alejandra; Mormandi, Eduardo; Alvarez Carbonetto, Elida M. del C.; Nowicki, Susana
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1?10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*?64%* (*p < 0.05 vs. control). This was explained by a reduction in cell proliferation (vehicle, 46 ± 3%; 1 μM, 23 ± 3%*; 10 μM, 28 ± 3%*) and by an increase in apoptosis (vehicle, 2.1 ± 0%; 1 μM, 16 ± 4%*; 10 μM, 31 ± 3%*). Furthermore, the increase in LNCaP cell viability induced by dihydrotestosterone (DHT, 0.1 nM) was abrogated by 30*?42%* by 1?10 μM HET0016. Incubation with 20-HETE (5?1000 nM) increased LNCaP cell viability up to 50%*, together with a 70%* reduction in apoptosis. PC-3 (androgen-insensitive) cell viability was not affected by either HET0016 or 20-HETE. In LNCaP cells, HET0016 (10 μM) diminished the expression of androgen receptors (AR): messenger RNA (mRNA) (40%*) and protein (50%*). DHT (10 nM) augmented CYP4F2 protein expression (1.9-fold*) and 20-HETE levels (50%*). Oppositely, enzalutamide (AR antagonist) reduced CYP4F2 mRNA and protein expressions by 30 and 25%, respectively. Thus, intracellular availability of 20-HETE is necessary to sustain LNCaP cell viability. 20-HETE may act as a signaling molecule in the pathways involved in LNCaP cell viability upon stimulation of the AR. This effect may be partially attributed to its role on securing normal AR expression levels that in turn contribute to maintain intracellular levels of 20-HETE.
Fil: Colombero Rivas, Cecilia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Sacca, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Mormandi, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos Dr. Carlos Durand; Argentina
Fil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Materia
20-Hydroxyeicosatetraenoic Acid
Prostate Cancer
Cyp4f2
Androgen Receptor
Lncap Cells
Apoptosis
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:11336/27523
Acceder
id CONICETDig_8b1433e71a4800d4ece6600810ef460b
oai_identifier_str oai:ri.conicet.gov.ar:11336/27523
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cellsColombero Rivas, Cecilia EdithPapademetrio, Daniela LauraSacca, Paula AlejandraMormandi, EduardoAlvarez Carbonetto, Elida M. del C.Nowicki, Susana20-Hydroxyeicosatetraenoic AcidProstate CancerCyp4f2Androgen ReceptorLncap CellsApoptosishttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/120-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1?10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*?64%* (*p < 0.05 vs. control). This was explained by a reduction in cell proliferation (vehicle, 46 ± 3%; 1 μM, 23 ± 3%*; 10 μM, 28 ± 3%*) and by an increase in apoptosis (vehicle, 2.1 ± 0%; 1 μM, 16 ± 4%*; 10 μM, 31 ± 3%*). Furthermore, the increase in LNCaP cell viability induced by dihydrotestosterone (DHT, 0.1 nM) was abrogated by 30*?42%* by 1?10 μM HET0016. Incubation with 20-HETE (5?1000 nM) increased LNCaP cell viability up to 50%*, together with a 70%* reduction in apoptosis. PC-3 (androgen-insensitive) cell viability was not affected by either HET0016 or 20-HETE. In LNCaP cells, HET0016 (10 μM) diminished the expression of androgen receptors (AR): messenger RNA (mRNA) (40%*) and protein (50%*). DHT (10 nM) augmented CYP4F2 protein expression (1.9-fold*) and 20-HETE levels (50%*). Oppositely, enzalutamide (AR antagonist) reduced CYP4F2 mRNA and protein expressions by 30 and 25%, respectively. Thus, intracellular availability of 20-HETE is necessary to sustain LNCaP cell viability. 20-HETE may act as a signaling molecule in the pathways involved in LNCaP cell viability upon stimulation of the AR. This effect may be partially attributed to its role on securing normal AR expression levels that in turn contribute to maintain intracellular levels of 20-HETE.Fil: Colombero Rivas, Cecilia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sacca, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mormandi, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos Dr. Carlos Durand; ArgentinaFil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaSpringer2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/27523Colombero Rivas, Cecilia Edith; Papademetrio, Daniela Laura; Sacca, Paula Alejandra; Mormandi, Eduardo; Alvarez Carbonetto, Elida M. del C.; et al.; Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells; Springer; Hormones and cancer; 8; 4; 8-2017; 243-2561868-84971868-8500CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s12672-017-0299-0info:eu-repo/semantics/altIdentifier/doi/10.1007/s12672-017-0299-0info:eu-repo/semantics/altIdentifier/pmid/28639228info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:00:26Zoai:ri.conicet.gov.ar:11336/27523instacron: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 13:00:26.914CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
title Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
spellingShingle Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
Colombero Rivas, Cecilia Edith
20-Hydroxyeicosatetraenoic Acid
Prostate Cancer
Cyp4f2
Androgen Receptor
Lncap Cells
Apoptosis
title_short Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
title_full Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
title_fullStr Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
title_full_unstemmed Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
title_sort Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells
dc.creator.none.fl_str_mv Colombero Rivas, Cecilia Edith
Papademetrio, Daniela Laura
Sacca, Paula Alejandra
Mormandi, Eduardo
Alvarez Carbonetto, Elida M. del C.
Nowicki, Susana
author Colombero Rivas, Cecilia Edith
author_facet Colombero Rivas, Cecilia Edith
Papademetrio, Daniela Laura
Sacca, Paula Alejandra
Mormandi, Eduardo
Alvarez Carbonetto, Elida M. del C.
Nowicki, Susana
author_role author
author2 Papademetrio, Daniela Laura
Sacca, Paula Alejandra
Mormandi, Eduardo
Alvarez Carbonetto, Elida M. del C.
Nowicki, Susana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 20-Hydroxyeicosatetraenoic Acid
Prostate Cancer
Cyp4f2
Androgen Receptor
Lncap Cells
Apoptosis
topic 20-Hydroxyeicosatetraenoic Acid
Prostate Cancer
Cyp4f2
Androgen Receptor
Lncap Cells
Apoptosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1?10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*?64%* (*p < 0.05 vs. control). This was explained by a reduction in cell proliferation (vehicle, 46 ± 3%; 1 μM, 23 ± 3%*; 10 μM, 28 ± 3%*) and by an increase in apoptosis (vehicle, 2.1 ± 0%; 1 μM, 16 ± 4%*; 10 μM, 31 ± 3%*). Furthermore, the increase in LNCaP cell viability induced by dihydrotestosterone (DHT, 0.1 nM) was abrogated by 30*?42%* by 1?10 μM HET0016. Incubation with 20-HETE (5?1000 nM) increased LNCaP cell viability up to 50%*, together with a 70%* reduction in apoptosis. PC-3 (androgen-insensitive) cell viability was not affected by either HET0016 or 20-HETE. In LNCaP cells, HET0016 (10 μM) diminished the expression of androgen receptors (AR): messenger RNA (mRNA) (40%*) and protein (50%*). DHT (10 nM) augmented CYP4F2 protein expression (1.9-fold*) and 20-HETE levels (50%*). Oppositely, enzalutamide (AR antagonist) reduced CYP4F2 mRNA and protein expressions by 30 and 25%, respectively. Thus, intracellular availability of 20-HETE is necessary to sustain LNCaP cell viability. 20-HETE may act as a signaling molecule in the pathways involved in LNCaP cell viability upon stimulation of the AR. This effect may be partially attributed to its role on securing normal AR expression levels that in turn contribute to maintain intracellular levels of 20-HETE.
Fil: Colombero Rivas, Cecilia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Papademetrio, Daniela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Sacca, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Mormandi, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos Dr. Carlos Durand; Argentina
Fil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Fil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
description 20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1?10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*?64%* (*p < 0.05 vs. control). This was explained by a reduction in cell proliferation (vehicle, 46 ± 3%; 1 μM, 23 ± 3%*; 10 μM, 28 ± 3%*) and by an increase in apoptosis (vehicle, 2.1 ± 0%; 1 μM, 16 ± 4%*; 10 μM, 31 ± 3%*). Furthermore, the increase in LNCaP cell viability induced by dihydrotestosterone (DHT, 0.1 nM) was abrogated by 30*?42%* by 1?10 μM HET0016. Incubation with 20-HETE (5?1000 nM) increased LNCaP cell viability up to 50%*, together with a 70%* reduction in apoptosis. PC-3 (androgen-insensitive) cell viability was not affected by either HET0016 or 20-HETE. In LNCaP cells, HET0016 (10 μM) diminished the expression of androgen receptors (AR): messenger RNA (mRNA) (40%*) and protein (50%*). DHT (10 nM) augmented CYP4F2 protein expression (1.9-fold*) and 20-HETE levels (50%*). Oppositely, enzalutamide (AR antagonist) reduced CYP4F2 mRNA and protein expressions by 30 and 25%, respectively. Thus, intracellular availability of 20-HETE is necessary to sustain LNCaP cell viability. 20-HETE may act as a signaling molecule in the pathways involved in LNCaP cell viability upon stimulation of the AR. This effect may be partially attributed to its role on securing normal AR expression levels that in turn contribute to maintain intracellular levels of 20-HETE.
publishDate 2017
dc.date.none.fl_str_mv 2017-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/27523
Colombero Rivas, Cecilia Edith; Papademetrio, Daniela Laura; Sacca, Paula Alejandra; Mormandi, Eduardo; Alvarez Carbonetto, Elida M. del C.; et al.; Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells; Springer; Hormones and cancer; 8; 4; 8-2017; 243-256
1868-8497
1868-8500
CONICET Digital
CONICET
url http://hdl.handle.net/11336/27523
identifier_str_mv Colombero Rivas, Cecilia Edith; Papademetrio, Daniela Laura; Sacca, Paula Alejandra; Mormandi, Eduardo; Alvarez Carbonetto, Elida M. del C.; et al.; Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in androgen-mediated cell viability in prostate cancer cells; Springer; Hormones and cancer; 8; 4; 8-2017; 243-256
1868-8497
1868-8500
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://link.springer.com/10.1007/s12672-017-0299-0
info:eu-repo/semantics/altIdentifier/doi/10.1007/s12672-017-0299-0
info:eu-repo/semantics/altIdentifier/pmid/28639228
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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