Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells
- Autores
- Vazquez, Ramiro; Riveiro, María Belén; Vermeulen, Elba Monica; Mondillo, Carolina; Coombes, Philip H.; Crouch, Neil R.; Ismail, Fathima; Mulholland, Dulcie A.; Baldi, Alberto; Shayo, Carina Claudia; Davio, Carlos Alberto
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Chemotherapeutics represent the main approach for the treatment of leukemia. However, the occurrence of adverse side effects and the complete lack of effectiveness in some cases make it necessary to develop new drugs. As part of our screening program to evaluate the potential chemotherapeutic effect of natural coumarins, we investigated the anti-leukemic activities of a series of six prenylated coumarins isolated from the stem bark of Toddalia asiatica (Rutaceae). Among these, 6-(3-methyl-2-butenyl)-5,7-dimethoxycoumarin (toddaculin) displayed the most potent cytotoxic and anti-proliferative effects in U-937 cells. To determine whether these effects resulted from induction of cell death or differentiation, we further evaluated the expression of several apoptosis and maturation markers. Interestingly, while toddaculin at 250 μM was able to induce apoptosis in U-937 cells, involving decreased phosphorylation levels of ERK and Akt, 50 μM toddaculin exerted differentiating effects, inducing both the capacity of U-937 cells to reduce NBT and the expression of differentiation markers CD88 and CD11b, but no change in p-Akt or p-ERK levels. Taken together, these findings indicate that toddaculin displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells, suggesting it may serve as a pharmacological prototype for the development of novel anti-leukemic agents.
Fil: Vazquez, Ramiro. 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: Riveiro, María Belén. 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: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Mondillo, Carolina. 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: Coombes, Philip H.. University of KwaZulu-Natal; Sudáfrica
Fil: Crouch, Neil R.. University of KwaZulu-Natal; Sudáfrica
Fil: Ismail, Fathima. University of KwaZulu-Natal; Sudáfrica
Fil: Mulholland, Dulcie A.. University of KwaZulu-Natal; Sudáfrica
Fil: Baldi, Alberto. 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: Shayo, Carina Claudia. 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: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina - Materia
-
Toddalia asiatica
Apoptosis
Differentiating activity
Leukemia - 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:11336/270683
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Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cellsVazquez, RamiroRiveiro, María BelénVermeulen, Elba MonicaMondillo, CarolinaCoombes, Philip H.Crouch, Neil R.Ismail, FathimaMulholland, Dulcie A.Baldi, AlbertoShayo, Carina ClaudiaDavio, Carlos AlbertoToddalia asiaticaApoptosisDifferentiating activityLeukemiahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Chemotherapeutics represent the main approach for the treatment of leukemia. However, the occurrence of adverse side effects and the complete lack of effectiveness in some cases make it necessary to develop new drugs. As part of our screening program to evaluate the potential chemotherapeutic effect of natural coumarins, we investigated the anti-leukemic activities of a series of six prenylated coumarins isolated from the stem bark of Toddalia asiatica (Rutaceae). Among these, 6-(3-methyl-2-butenyl)-5,7-dimethoxycoumarin (toddaculin) displayed the most potent cytotoxic and anti-proliferative effects in U-937 cells. To determine whether these effects resulted from induction of cell death or differentiation, we further evaluated the expression of several apoptosis and maturation markers. Interestingly, while toddaculin at 250 μM was able to induce apoptosis in U-937 cells, involving decreased phosphorylation levels of ERK and Akt, 50 μM toddaculin exerted differentiating effects, inducing both the capacity of U-937 cells to reduce NBT and the expression of differentiation markers CD88 and CD11b, but no change in p-Akt or p-ERK levels. Taken together, these findings indicate that toddaculin displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells, suggesting it may serve as a pharmacological prototype for the development of novel anti-leukemic agents.Fil: Vazquez, Ramiro. 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: Riveiro, María Belén. 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: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Mondillo, Carolina. 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: Coombes, Philip H.. University of KwaZulu-Natal; SudáfricaFil: Crouch, Neil R.. University of KwaZulu-Natal; SudáfricaFil: Ismail, Fathima. University of KwaZulu-Natal; SudáfricaFil: Mulholland, Dulcie A.. University of KwaZulu-Natal; SudáfricaFil: Baldi, Alberto. 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: Shayo, Carina Claudia. 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: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaElsevier Gmbh2012-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/270683Vazquez, Ramiro; Riveiro, María Belén; Vermeulen, Elba Monica; Mondillo, Carolina; Coombes, Philip H.; et al.; Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells; Elsevier Gmbh; Phytomedicine; 19; 8-9; 6-2012; 737-7460944-7113CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S094471131200092Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2012.03.008info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:07Zoai:ri.conicet.gov.ar:11336/270683instacron: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 09:44:08.221CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells |
title |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells |
spellingShingle |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells Vazquez, Ramiro Toddalia asiatica Apoptosis Differentiating activity Leukemia |
title_short |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells |
title_full |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells |
title_fullStr |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells |
title_full_unstemmed |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells |
title_sort |
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells |
dc.creator.none.fl_str_mv |
Vazquez, Ramiro Riveiro, María Belén Vermeulen, Elba Monica Mondillo, Carolina Coombes, Philip H. Crouch, Neil R. Ismail, Fathima Mulholland, Dulcie A. Baldi, Alberto Shayo, Carina Claudia Davio, Carlos Alberto |
author |
Vazquez, Ramiro |
author_facet |
Vazquez, Ramiro Riveiro, María Belén Vermeulen, Elba Monica Mondillo, Carolina Coombes, Philip H. Crouch, Neil R. Ismail, Fathima Mulholland, Dulcie A. Baldi, Alberto Shayo, Carina Claudia Davio, Carlos Alberto |
author_role |
author |
author2 |
Riveiro, María Belén Vermeulen, Elba Monica Mondillo, Carolina Coombes, Philip H. Crouch, Neil R. Ismail, Fathima Mulholland, Dulcie A. Baldi, Alberto Shayo, Carina Claudia Davio, Carlos Alberto |
author2_role |
author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Toddalia asiatica Apoptosis Differentiating activity Leukemia |
topic |
Toddalia asiatica Apoptosis Differentiating activity Leukemia |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Chemotherapeutics represent the main approach for the treatment of leukemia. However, the occurrence of adverse side effects and the complete lack of effectiveness in some cases make it necessary to develop new drugs. As part of our screening program to evaluate the potential chemotherapeutic effect of natural coumarins, we investigated the anti-leukemic activities of a series of six prenylated coumarins isolated from the stem bark of Toddalia asiatica (Rutaceae). Among these, 6-(3-methyl-2-butenyl)-5,7-dimethoxycoumarin (toddaculin) displayed the most potent cytotoxic and anti-proliferative effects in U-937 cells. To determine whether these effects resulted from induction of cell death or differentiation, we further evaluated the expression of several apoptosis and maturation markers. Interestingly, while toddaculin at 250 μM was able to induce apoptosis in U-937 cells, involving decreased phosphorylation levels of ERK and Akt, 50 μM toddaculin exerted differentiating effects, inducing both the capacity of U-937 cells to reduce NBT and the expression of differentiation markers CD88 and CD11b, but no change in p-Akt or p-ERK levels. Taken together, these findings indicate that toddaculin displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells, suggesting it may serve as a pharmacological prototype for the development of novel anti-leukemic agents. Fil: Vazquez, Ramiro. 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: Riveiro, María Belén. 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: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Mondillo, Carolina. 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: Coombes, Philip H.. University of KwaZulu-Natal; Sudáfrica Fil: Crouch, Neil R.. University of KwaZulu-Natal; Sudáfrica Fil: Ismail, Fathima. University of KwaZulu-Natal; Sudáfrica Fil: Mulholland, Dulcie A.. University of KwaZulu-Natal; Sudáfrica Fil: Baldi, Alberto. 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: Shayo, Carina Claudia. 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: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina |
description |
Chemotherapeutics represent the main approach for the treatment of leukemia. However, the occurrence of adverse side effects and the complete lack of effectiveness in some cases make it necessary to develop new drugs. As part of our screening program to evaluate the potential chemotherapeutic effect of natural coumarins, we investigated the anti-leukemic activities of a series of six prenylated coumarins isolated from the stem bark of Toddalia asiatica (Rutaceae). Among these, 6-(3-methyl-2-butenyl)-5,7-dimethoxycoumarin (toddaculin) displayed the most potent cytotoxic and anti-proliferative effects in U-937 cells. To determine whether these effects resulted from induction of cell death or differentiation, we further evaluated the expression of several apoptosis and maturation markers. Interestingly, while toddaculin at 250 μM was able to induce apoptosis in U-937 cells, involving decreased phosphorylation levels of ERK and Akt, 50 μM toddaculin exerted differentiating effects, inducing both the capacity of U-937 cells to reduce NBT and the expression of differentiation markers CD88 and CD11b, but no change in p-Akt or p-ERK levels. Taken together, these findings indicate that toddaculin displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells, suggesting it may serve as a pharmacological prototype for the development of novel anti-leukemic agents. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-06 |
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/11336/270683 Vazquez, Ramiro; Riveiro, María Belén; Vermeulen, Elba Monica; Mondillo, Carolina; Coombes, Philip H.; et al.; Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells; Elsevier Gmbh; Phytomedicine; 19; 8-9; 6-2012; 737-746 0944-7113 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/270683 |
identifier_str_mv |
Vazquez, Ramiro; Riveiro, María Belén; Vermeulen, Elba Monica; Mondillo, Carolina; Coombes, Philip H.; et al.; Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells; Elsevier Gmbh; Phytomedicine; 19; 8-9; 6-2012; 737-746 0944-7113 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.sciencedirect.com/science/article/abs/pii/S094471131200092X info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2012.03.008 |
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 application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier Gmbh |
publisher.none.fl_str_mv |
Elsevier Gmbh |
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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1844613388955549696 |
score |
13.070432 |