Repositioning of bromocriptine for treatment of acute myeloid leukemia

Journal of Translational Medicine

Research

María Carmen Lara-Castillo¹  Antònia Banús-Mulet¹  Josep Maria Cornet-Masana¹  Ruth M. Risueño¹  Amaia Etxabe¹  Miguel Ángel Torrente²  Meritxell Nomdedeu²  Marina Díaz-Beyá³  Jordi Esteve³ 

[1] Centre Esther Koplowitz, Josep Carreras Leukaemia Research Institute, Campus Clínic-University of Barcelona, Rosselló 149-153, 08036, Barcelona, Spain;Centre Esther Koplowitz, Josep Carreras Leukaemia Research Institute, Campus Clínic-University of Barcelona, Rosselló 149-153, 08036, Barcelona, Spain;Department of Hematology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;Centre Esther Koplowitz, Josep Carreras Leukaemia Research Institute, Campus Clínic-University of Barcelona, Rosselló 149-153, 08036, Barcelona, Spain;Department of Hematology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;University of Barcelona, Barcelona, Spain;

关键词: AML;    Bromocriptine;    New drug;    Drug repositioning;    Leukemia stem cells;   

DOI  :  10.1186/s12967-016-1007-5

 received in 2016-06-15, accepted in 2016-08-16,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundTreatment for acute myeloid leukemia (AML) has not significantly changed in the last decades and new therapeutic approaches are needed to achieve prolonged survival rates. Leukemia stem cells (LSC) are responsible for the initiation and maintenance of AML due to their stem-cell properties. Differentiation therapies aim to abrogate the self-renewal capacity and diminish blast lifespan.MethodsAn in silico screening was designed to search for FDA-approved small molecules that potentially induce differentiation of AML cells. Bromocriptine was identified and validated in an in vitro screening. Bromocriptine is an approved drug originally indicated for Parkinson’s disease, acromegaly, hyperprolactinemia and galactorrhoea, and recently repositioned for diabetes mellitus.ResultsTreatment with bromocriptine reduced cell viability of AML cells by activation of the apoptosis program and induction of myeloid differentiation. Moreover, the LSC-enriched primitive AML cell fraction was more sensitive to the presence of bromocriptine. In fact, bromocriptine decreased the clonogenic capacity of AML cells. Interestingly, a negligible effect is observed in healthy blood cells and hematopoietic stem/progenitor cells.ConclusionsOur results support the use of bromocriptine as an anti-AML drug in a repositioning setting and the further clinical validation of this preclinical study.

【 授权许可】

CC BY   
© The Author(s) 2016