Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment
- Autores
- Callero, Mariana Alejandra; Suárez, Guadalupe V.; Luzzani, Gabriela Andrea; Itkin, Boris; Nguyen, Binh; Loaiza Perez, Andrea Irene
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Aminoflavone (AF; NSC 686288, AFP464, NSC710464) is a new anticancer drug that has recently entered phase II clinical trials. It has demonstrated antiproliferative effects in MCF-7 human breast cancer cells mediated by the aryl hydrocarbon receptor (AhR). AF also exhibits noteworthy evidence of antitumor activity in vitro and in vivo against neoplastic cells of renal origin. AF treatment of sensitive renal cells, in contrast to resistant cells, promotes the induction of CYP1A1, the covalent binding of AF-reactive intermediates and apoptosis. Based on this evidence, the aim of this study was to evaluate the role of AhR, the main transcriptional regulator of CYP1A1, in the antiproliferative effects of AF in human renal cancer cells. AF-cytoxicity in human renal cell lines and a renal cancer cell strain was assessed by MTS assay in the presence or absence of an Ahr inhibitor. Drug-induced AhR nuclear translocation was evaluated by western blotting of AhR in cytosolic and nuclear fractions and by measuring xenobiotic response element-driven luciferase activity. Apoptosis induced by the drug was evaluated by 4,6-diamidino-2-phenylindole and acridine orange/ethidium bromide staining and by measuring phosphorylated P53 (p-P53) and P21 levels, caspase 3 activation and poly(ADP-ribose) polymerase cleavage. AF inhibited cell growth in a dose-dependent manner in TK-10, Caki-1, SN12-C and A498 human renal cells but not in ACHN cells. The antiproliferative effect of AF was abrogated by pre-incubation of TK-10, Caki-1 and SN12-C cells with the AhR antagonist, α-naphthoflavone. AF treatment also induced apoptosis in TK-10, Caki-1 and SN12-C cells, which was not observed in ACHN cells. AF induced time-dependent AhR nuclear translocation and AhR transcriptional activity in sensitive renal cancer cell lines. A renal cell strain derived from a human papillary tumor also showed sensitivity to AF, as well as AhR pathway activation and drug-induced apoptosis. AhR translocation could be included as a marker of sensitivity to AF in sensitive renal tumor cells of different histological origin, in ongoing phase II clinical trials.
Fil: Callero, Mariana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Suárez, Guadalupe V.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Luzzani, Gabriela Andrea. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Itkin, Boris. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina
Fil: Nguyen, Binh. Tigris Pharmaceuticals Inc.; Estados Unidos
Fil: Loaiza Perez, Andrea Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina - Materia
-
ARYL HYDROCARBON RECEPTOR
CYTOCHROME P450 1A1
RENAL CANCER
APOPTOSIS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/269490
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Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatmentCallero, Mariana AlejandraSuárez, Guadalupe V.Luzzani, Gabriela AndreaItkin, BorisNguyen, BinhLoaiza Perez, Andrea IreneARYL HYDROCARBON RECEPTORCYTOCHROME P450 1A1RENAL CANCERAPOPTOSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Aminoflavone (AF; NSC 686288, AFP464, NSC710464) is a new anticancer drug that has recently entered phase II clinical trials. It has demonstrated antiproliferative effects in MCF-7 human breast cancer cells mediated by the aryl hydrocarbon receptor (AhR). AF also exhibits noteworthy evidence of antitumor activity in vitro and in vivo against neoplastic cells of renal origin. AF treatment of sensitive renal cells, in contrast to resistant cells, promotes the induction of CYP1A1, the covalent binding of AF-reactive intermediates and apoptosis. Based on this evidence, the aim of this study was to evaluate the role of AhR, the main transcriptional regulator of CYP1A1, in the antiproliferative effects of AF in human renal cancer cells. AF-cytoxicity in human renal cell lines and a renal cancer cell strain was assessed by MTS assay in the presence or absence of an Ahr inhibitor. Drug-induced AhR nuclear translocation was evaluated by western blotting of AhR in cytosolic and nuclear fractions and by measuring xenobiotic response element-driven luciferase activity. Apoptosis induced by the drug was evaluated by 4,6-diamidino-2-phenylindole and acridine orange/ethidium bromide staining and by measuring phosphorylated P53 (p-P53) and P21 levels, caspase 3 activation and poly(ADP-ribose) polymerase cleavage. AF inhibited cell growth in a dose-dependent manner in TK-10, Caki-1, SN12-C and A498 human renal cells but not in ACHN cells. The antiproliferative effect of AF was abrogated by pre-incubation of TK-10, Caki-1 and SN12-C cells with the AhR antagonist, α-naphthoflavone. AF treatment also induced apoptosis in TK-10, Caki-1 and SN12-C cells, which was not observed in ACHN cells. AF induced time-dependent AhR nuclear translocation and AhR transcriptional activity in sensitive renal cancer cell lines. A renal cell strain derived from a human papillary tumor also showed sensitivity to AF, as well as AhR pathway activation and drug-induced apoptosis. AhR translocation could be included as a marker of sensitivity to AF in sensitive renal tumor cells of different histological origin, in ongoing phase II clinical trials.Fil: Callero, Mariana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Suárez, Guadalupe V.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Luzzani, Gabriela Andrea. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Itkin, Boris. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Nguyen, Binh. Tigris Pharmaceuticals Inc.; Estados UnidosFil: Loaiza Perez, Andrea Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaSpandidos Publications2012-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/269490Callero, Mariana Alejandra; Suárez, Guadalupe V.; Luzzani, Gabriela Andrea; Itkin, Boris; Nguyen, Binh; et al.; Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment; Spandidos Publications; International Journal of Oncology; 41; 4-2012; 125-1341019-6439CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/ijo/41/1/125info:eu-repo/semantics/altIdentifier/doi/10.3892/ijo.2012.1427info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:40:39Zoai:ri.conicet.gov.ar:11336/269490instacron: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:34982025-09-29 10:40:39.673CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment |
title |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment |
spellingShingle |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment Callero, Mariana Alejandra ARYL HYDROCARBON RECEPTOR CYTOCHROME P450 1A1 RENAL CANCER APOPTOSIS |
title_short |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment |
title_full |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment |
title_fullStr |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment |
title_full_unstemmed |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment |
title_sort |
Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment |
dc.creator.none.fl_str_mv |
Callero, Mariana Alejandra Suárez, Guadalupe V. Luzzani, Gabriela Andrea Itkin, Boris Nguyen, Binh Loaiza Perez, Andrea Irene |
author |
Callero, Mariana Alejandra |
author_facet |
Callero, Mariana Alejandra Suárez, Guadalupe V. Luzzani, Gabriela Andrea Itkin, Boris Nguyen, Binh Loaiza Perez, Andrea Irene |
author_role |
author |
author2 |
Suárez, Guadalupe V. Luzzani, Gabriela Andrea Itkin, Boris Nguyen, Binh Loaiza Perez, Andrea Irene |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
ARYL HYDROCARBON RECEPTOR CYTOCHROME P450 1A1 RENAL CANCER APOPTOSIS |
topic |
ARYL HYDROCARBON RECEPTOR CYTOCHROME P450 1A1 RENAL CANCER 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 |
Aminoflavone (AF; NSC 686288, AFP464, NSC710464) is a new anticancer drug that has recently entered phase II clinical trials. It has demonstrated antiproliferative effects in MCF-7 human breast cancer cells mediated by the aryl hydrocarbon receptor (AhR). AF also exhibits noteworthy evidence of antitumor activity in vitro and in vivo against neoplastic cells of renal origin. AF treatment of sensitive renal cells, in contrast to resistant cells, promotes the induction of CYP1A1, the covalent binding of AF-reactive intermediates and apoptosis. Based on this evidence, the aim of this study was to evaluate the role of AhR, the main transcriptional regulator of CYP1A1, in the antiproliferative effects of AF in human renal cancer cells. AF-cytoxicity in human renal cell lines and a renal cancer cell strain was assessed by MTS assay in the presence or absence of an Ahr inhibitor. Drug-induced AhR nuclear translocation was evaluated by western blotting of AhR in cytosolic and nuclear fractions and by measuring xenobiotic response element-driven luciferase activity. Apoptosis induced by the drug was evaluated by 4,6-diamidino-2-phenylindole and acridine orange/ethidium bromide staining and by measuring phosphorylated P53 (p-P53) and P21 levels, caspase 3 activation and poly(ADP-ribose) polymerase cleavage. AF inhibited cell growth in a dose-dependent manner in TK-10, Caki-1, SN12-C and A498 human renal cells but not in ACHN cells. The antiproliferative effect of AF was abrogated by pre-incubation of TK-10, Caki-1 and SN12-C cells with the AhR antagonist, α-naphthoflavone. AF treatment also induced apoptosis in TK-10, Caki-1 and SN12-C cells, which was not observed in ACHN cells. AF induced time-dependent AhR nuclear translocation and AhR transcriptional activity in sensitive renal cancer cell lines. A renal cell strain derived from a human papillary tumor also showed sensitivity to AF, as well as AhR pathway activation and drug-induced apoptosis. AhR translocation could be included as a marker of sensitivity to AF in sensitive renal tumor cells of different histological origin, in ongoing phase II clinical trials. Fil: Callero, Mariana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Suárez, Guadalupe V.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Luzzani, Gabriela Andrea. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Itkin, Boris. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Nguyen, Binh. Tigris Pharmaceuticals Inc.; Estados Unidos Fil: Loaiza Perez, Andrea Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina |
description |
Aminoflavone (AF; NSC 686288, AFP464, NSC710464) is a new anticancer drug that has recently entered phase II clinical trials. It has demonstrated antiproliferative effects in MCF-7 human breast cancer cells mediated by the aryl hydrocarbon receptor (AhR). AF also exhibits noteworthy evidence of antitumor activity in vitro and in vivo against neoplastic cells of renal origin. AF treatment of sensitive renal cells, in contrast to resistant cells, promotes the induction of CYP1A1, the covalent binding of AF-reactive intermediates and apoptosis. Based on this evidence, the aim of this study was to evaluate the role of AhR, the main transcriptional regulator of CYP1A1, in the antiproliferative effects of AF in human renal cancer cells. AF-cytoxicity in human renal cell lines and a renal cancer cell strain was assessed by MTS assay in the presence or absence of an Ahr inhibitor. Drug-induced AhR nuclear translocation was evaluated by western blotting of AhR in cytosolic and nuclear fractions and by measuring xenobiotic response element-driven luciferase activity. Apoptosis induced by the drug was evaluated by 4,6-diamidino-2-phenylindole and acridine orange/ethidium bromide staining and by measuring phosphorylated P53 (p-P53) and P21 levels, caspase 3 activation and poly(ADP-ribose) polymerase cleavage. AF inhibited cell growth in a dose-dependent manner in TK-10, Caki-1, SN12-C and A498 human renal cells but not in ACHN cells. The antiproliferative effect of AF was abrogated by pre-incubation of TK-10, Caki-1 and SN12-C cells with the AhR antagonist, α-naphthoflavone. AF treatment also induced apoptosis in TK-10, Caki-1 and SN12-C cells, which was not observed in ACHN cells. AF induced time-dependent AhR nuclear translocation and AhR transcriptional activity in sensitive renal cancer cell lines. A renal cell strain derived from a human papillary tumor also showed sensitivity to AF, as well as AhR pathway activation and drug-induced apoptosis. AhR translocation could be included as a marker of sensitivity to AF in sensitive renal tumor cells of different histological origin, in ongoing phase II clinical trials. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-04 |
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/11336/269490 Callero, Mariana Alejandra; Suárez, Guadalupe V.; Luzzani, Gabriela Andrea; Itkin, Boris; Nguyen, Binh; et al.; Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment; Spandidos Publications; International Journal of Oncology; 41; 4-2012; 125-134 1019-6439 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/269490 |
identifier_str_mv |
Callero, Mariana Alejandra; Suárez, Guadalupe V.; Luzzani, Gabriela Andrea; Itkin, Boris; Nguyen, Binh; et al.; Aryl hydrocarbon receptor activation by aminoflavone: New molecular target for renal cancer treatment; Spandidos Publications; International Journal of Oncology; 41; 4-2012; 125-134 1019-6439 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/ijo/41/1/125 info:eu-repo/semantics/altIdentifier/doi/10.3892/ijo.2012.1427 |
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 |
dc.publisher.none.fl_str_mv |
Spandidos Publications |
publisher.none.fl_str_mv |
Spandidos Publications |
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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1844614435379871744 |
score |
13.070432 |