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Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity.
- Source :
-
Scientific reports [Sci Rep] 2017 Mar 07; Vol. 7, pp. 43930. Date of Electronic Publication: 2017 Mar 07. - Publication Year :
- 2017
-
Abstract
- Maintaining stemness of leukemic stem cells (LSCs) and reciprocal interactions between leukemia and stromal cells support leukemic progression and resistance to chemotherapy. Targeting the niche-based microenvironment is thus a new approach for leukemia therapy. Cordycepin is an analogue of adenosine and has been suggested to possess anti-leukemia properties. However, whether cordycepin influences association of leukemia and mesenchymal stromal cells has never been investigated. Here we show that cordycepin reduces CD34 <superscript>+</superscript> CD38 <superscript>-</superscript> cells in U937 and K562 cells and induces Dkk1 expression via autocrine and paracrine regulation in leukemia and mesenchymal stromal/stem cells (MSCs). Cordycepin suppresses cell attachment of leukemia with MSCs and downregulates N-cadherin in leukemia and VCAM-1 in MSCs. Moreover, incubation with leukemic conditioned media (CM) significantly induces IL-8 and IL-6 expression in MSCs, which is abrogated by cordycepin. Suppression of leukemic CM-induced VCAM-1 and IL-8 by cordycepin in MSCs is mediated by impairing NFκB signaling. Finally, cordycepin combined with an adenosine deaminase inhibitor prolongs survival in a leukemic mouse model. Our results indicate that cordycepin is a potential anti-leukemia therapeutic adjuvant via eliminating LSCs and disrupting leukemia-stromal association.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Cell Adhesion drug effects
Deoxyadenosines administration & dosage
Disease Models, Animal
Humans
K562 Cells
Leukemia pathology
Mice
Survival Analysis
Treatment Outcome
U937 Cells
Antineoplastic Agents pharmacology
Deoxyadenosines pharmacology
Leukemia drug therapy
Mesenchymal Stem Cells drug effects
Mesenchymal Stem Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28266575
- Full Text :
- https://doi.org/10.1038/srep43930