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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells
Phytomedicine, Volume 19, No. 8-9, Year 2012
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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. © 2012 Elsevier GmbH. All rights reserved.
Authors & Co-Authors
Vázquez, Ramiro
Argentina, Buenos Aires
Consejo Nacional de Investigaciones Científicas y Técnicas
Argentina, Buenos Aires
Universidad de Buenos Aires
Riveiro, María E.
Argentina, Buenos Aires
Consejo Nacional de Investigaciones Científicas y Técnicas
Vermeulen, Mónica
Argentina, Buenos Aires
Instituto de Investigaciones Hematológicas
Mondillo, Carolina
Argentina, Buenos Aires
Consejo Nacional de Investigaciones Científicas y Técnicas
Coombes, Philip H.
South Africa, Durban
University of Kwazulu-natal
Crouch, Neil R.
South Africa, Durban
University of Kwazulu-natal
South Africa, Pretoria
South African National Biodiversity Institute
Ismail, Fathima
South Africa, Durban
University of Kwazulu-natal
Mulholland, D. A.
South Africa, Durban
University of Kwazulu-natal
United Kingdom, Guildford
University of Surrey
Baldi, Alberto
Argentina, Buenos Aires
Consejo Nacional de Investigaciones Científicas y Técnicas
Shayo, Carina
Argentina, Buenos Aires
Consejo Nacional de Investigaciones Científicas y Técnicas
Davio, Carlos
Argentina, Buenos Aires
Universidad de Buenos Aires
Statistics
Citations: 46
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1016/j.phymed.2012.03.008
ISSN:
09447113
e-ISSN:
1618095X
Research Areas
Cancer