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Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways

Differentiation therapy with all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), has been extremely successful in inducing clinical remission in APL patients. However, the differentiation therapy of ATRA-based treatment has not been effect...

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Autores principales: Qu, Mei, Duan, Yu, Zhao, Min, Wang, Zhanju, Zhao, Mengjie, Zhao, Yao, Wang, Haihua, Ke, Yu, Liu, Ying, Liu, Hong-Min, Wei, Liuya, Hu, Zhenbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033199/
https://www.ncbi.nlm.nih.gov/pubmed/33842376
http://dx.doi.org/10.3389/fonc.2021.659720
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author Qu, Mei
Duan, Yu
Zhao, Min
Wang, Zhanju
Zhao, Mengjie
Zhao, Yao
Wang, Haihua
Ke, Yu
Liu, Ying
Liu, Hong-Min
Wei, Liuya
Hu, Zhenbo
author_facet Qu, Mei
Duan, Yu
Zhao, Min
Wang, Zhanju
Zhao, Mengjie
Zhao, Yao
Wang, Haihua
Ke, Yu
Liu, Ying
Liu, Hong-Min
Wei, Liuya
Hu, Zhenbo
author_sort Qu, Mei
collection PubMed
description Differentiation therapy with all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), has been extremely successful in inducing clinical remission in APL patients. However, the differentiation therapy of ATRA-based treatment has not been effective in other subtypes of AML. In this study, we evaluated a small molecule of ent-kaurene diterpenoid, Jiyuan oridonin A (JOA), on the differentiation blockade in AML cells with the mixed lineage leukemia (MLL) gene rearrangements (MLLr) in MV4-11, MOLM-13 and THP-1 cells. We found that JOA could significantly inhibit the proliferation of MOLM-13, MV4-11 and THP-1 cells. Moreover, JOA promoted cell differentiation coupled with cell-cycle exit at G0/G1 and inhibited the colony- forming capacity of these cells. We showed that the anti-proliferative effect of JOA attributed to cell differentiation is most likely through the martens tretinoin response up pathway in the MOLM-13 cell line, and the hematopoietic cell lineage pathway by the inhibition of c-KIT expression and cell adhesion pathway in the THP-1 cell line. Our findings suggest that JOA could be a novel therapeutic agent against human MLLr acute myeloid leukemia.
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spelling pubmed-80331992021-04-10 Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways Qu, Mei Duan, Yu Zhao, Min Wang, Zhanju Zhao, Mengjie Zhao, Yao Wang, Haihua Ke, Yu Liu, Ying Liu, Hong-Min Wei, Liuya Hu, Zhenbo Front Oncol Oncology Differentiation therapy with all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), has been extremely successful in inducing clinical remission in APL patients. However, the differentiation therapy of ATRA-based treatment has not been effective in other subtypes of AML. In this study, we evaluated a small molecule of ent-kaurene diterpenoid, Jiyuan oridonin A (JOA), on the differentiation blockade in AML cells with the mixed lineage leukemia (MLL) gene rearrangements (MLLr) in MV4-11, MOLM-13 and THP-1 cells. We found that JOA could significantly inhibit the proliferation of MOLM-13, MV4-11 and THP-1 cells. Moreover, JOA promoted cell differentiation coupled with cell-cycle exit at G0/G1 and inhibited the colony- forming capacity of these cells. We showed that the anti-proliferative effect of JOA attributed to cell differentiation is most likely through the martens tretinoin response up pathway in the MOLM-13 cell line, and the hematopoietic cell lineage pathway by the inhibition of c-KIT expression and cell adhesion pathway in the THP-1 cell line. Our findings suggest that JOA could be a novel therapeutic agent against human MLLr acute myeloid leukemia. Frontiers Media S.A. 2021-03-26 /pmc/articles/PMC8033199/ /pubmed/33842376 http://dx.doi.org/10.3389/fonc.2021.659720 Text en Copyright © 2021 Qu, Duan, Zhao, Wang, Zhao, Zhao, Wang, Ke, Liu, Liu, Wei and Hu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Qu, Mei
Duan, Yu
Zhao, Min
Wang, Zhanju
Zhao, Mengjie
Zhao, Yao
Wang, Haihua
Ke, Yu
Liu, Ying
Liu, Hong-Min
Wei, Liuya
Hu, Zhenbo
Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways
title Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways
title_full Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways
title_fullStr Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways
title_full_unstemmed Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways
title_short Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways
title_sort jiyuan oridonin a overcomes differentiation blockade in acute myeloid leukemia cells with mll rearrangements via multiple signaling pathways
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033199/
https://www.ncbi.nlm.nih.gov/pubmed/33842376
http://dx.doi.org/10.3389/fonc.2021.659720
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