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Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity
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 adenosin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339716/ https://www.ncbi.nlm.nih.gov/pubmed/28266575 http://dx.doi.org/10.1038/srep43930 |
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author | Liang, Shu-Man Lu, Yi-Jhu Ko, Bor-Sheng Jan, Yee-Jee Shyue, Song-Kun Yet, Shaw-Fang Liou, Jun-Yang |
author_facet | Liang, Shu-Man Lu, Yi-Jhu Ko, Bor-Sheng Jan, Yee-Jee Shyue, Song-Kun Yet, Shaw-Fang Liou, Jun-Yang |
author_sort | Liang, Shu-Man |
collection | PubMed |
description | 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(+)CD38(−) 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. |
format | Online Article Text |
id | pubmed-5339716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53397162017-03-10 Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity Liang, Shu-Man Lu, Yi-Jhu Ko, Bor-Sheng Jan, Yee-Jee Shyue, Song-Kun Yet, Shaw-Fang Liou, Jun-Yang Sci Rep Article 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(+)CD38(−) 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. Nature Publishing Group 2017-03-07 /pmc/articles/PMC5339716/ /pubmed/28266575 http://dx.doi.org/10.1038/srep43930 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Liang, Shu-Man Lu, Yi-Jhu Ko, Bor-Sheng Jan, Yee-Jee Shyue, Song-Kun Yet, Shaw-Fang Liou, Jun-Yang Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity |
title | Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity |
title_full | Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity |
title_fullStr | Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity |
title_full_unstemmed | Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity |
title_short | Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity |
title_sort | cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339716/ https://www.ncbi.nlm.nih.gov/pubmed/28266575 http://dx.doi.org/10.1038/srep43930 |
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