Journal article
Monocyte-macrophage differentiation of acute myeloid leukemia cell lines by small molecules identified through interrogation of the Connectivity Map database
Cell cycle (Georgetown, Tex.), v 14(16), pp 2578-2589
18 Aug 2015
PMID: 26102293
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The transcription factor C/EBPα is required for granulocytic differentiation of normal myeloid progenitors and is frequently inactivated in acute myeloid leukemia (AML) cells. Ectopic expression of C/EBPα in AML cells suppresses proliferation and induces differentiation suggesting that restoring C/EBPα expression/activity in AML cells could be therapeutically useful. Unfortunately, current approaches of gene or protein delivery in leukemic cells are unsatisfactory. However, "drug repurposing" is becoming a very attractive strategy to identify potential new uses for existing drugs. In this study, we assessed the biological effects of candidate C/EBPα-mimetics identified by interrogation of the Connectivity Map database. We found that amantadine, an antiviral and anti-Parkinson agent, induced a monocyte-macrophage-like differentiation of HL60, U937, Kasumi-1 myeloid leukemia cell lines, as indicated by morphology and differentiation antigen expression, when used in combination with suboptimal concentration of all trans retinoic acid (ATRA) or Vit D3. The effect of amantadine depends, in part, on increased activity of the vitamin D receptor (VDR), since it induced VDR expression and amantadine-dependent monocyte-macrophage differentiation of HL60 cells was blocked by expression of dominant-negative VDR. These results reveal a new function for amantadine and support the concept that screening of the Connectivity Map database can identify small molecules that mimic the effect of transcription factors required for myelo-monocytic differentiation.
Metrics
Details
- Title
- Monocyte-macrophage differentiation of acute myeloid leukemia cell lines by small molecules identified through interrogation of the Connectivity Map database
- Creators
- Gloria Manzotti - a Department of Diagnostic and Clinical Medicine and Public HealthSandra Parenti - University of Modena and Reggio EmiliaGiovanna Ferrari-Amorotti - Modena , Italy.Angela Rachele Soliera - University of Modena and Reggio EmiliaSara Cattelani - University of Modena and Reggio EmiliaMonica Montanari - University of Modena and Reggio EmiliaDaniel Cavalli - University of Modena and Reggio EmiliaAdam Ertel - Sidney Kimmel Cancer CenterAlexis Grande - University of Modena and Reggio EmiliaBruno Calabretta - Department of Diagnostic and Clinical Medicine and Public Health; University of Modena and R. Emilia; Modena, Italy; Department of Cancer Biology and Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA
- Publication Details
- Cell cycle (Georgetown, Tex.), v 14(16), pp 2578-2589
- Publisher
- Taylor & Francis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000360295400017
- Scopus ID
- 2-s2.0-84943775569
- Other Identifier
- 991019176648004721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology