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

被引:9
作者
Qu, Mei [1 ,2 ]
Duan, Yu [1 ,2 ]
Zhao, Min [1 ,2 ]
Wang, Zhanju [1 ]
Zhao, Mengjie [1 ,2 ]
Zhao, Yao [1 ]
Wang, Haihua [1 ]
Ke, Yu [3 ]
Liu, Ying [3 ]
Liu, Hong-Min [3 ]
Wei, Liuya [1 ,2 ]
Hu, Zhenbo [1 ,2 ]
机构
[1] Weifang Med Univ, Lab Stem Cell & Regenerat Med, Affiliated Hosp, Weifang, Peoples R China
[2] Weifang Med Univ, Sch Pharm, Weifang, Peoples R China
[3] Zhengzhou Univ, Sch Pharm, Zhengzhou, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2021年 / 11卷
基金
中国国家自然科学基金;
关键词
differentiation therapy; acute myeloid leukemia with MLL gene rearrangements; Jiyuan oridonin A; martens tretinoin response up pathway; hematopoietic cell lineage pathway; cell adhesion pathway;
D O I
10.3389/fonc.2021.659720
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:11
相关论文
共 33 条
[1]   Therapeutic targeting of c-KIT in cancer [J].
Ashman, Leonie K. ;
Griffith, Renate .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2013, 22 (01) :103-115
[2]  
Asmaa Mat Jusoh Siti, 2020, Int J Hematol Oncol Stem Cell Res, V14, P72
[3]   Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy [J].
Carter, Jenna L. ;
Hege, Katie ;
Yang, Jay ;
Kalpage, Hasini A. ;
Su, Yongwei ;
Edwards, Holly ;
Huttemann, Maik ;
Taub, Jeffrey W. ;
Ge, Yubin .
SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2020, 5 (01)
[4]   CD99 is a therapeutic target on disease stem cells in myeloid malignancies [J].
Chung, Stephen S. ;
Eng, William S. ;
Hu, Wenhuo ;
Khalaj, Mona ;
Garrett-Bakelman, Francine E. ;
Tavakkoli, Montreh ;
Levine, Ross L. ;
Carroll, Martin ;
Klimek, Virginia M. ;
Melnick, Ari M. ;
Park, Christopher Y. .
SCIENCE TRANSLATIONAL MEDICINE, 2017, 9 (374)
[5]   Adult Acute Leukemia [J].
Cornell, Robert Frank ;
Palmer, Jeanne .
DM DISEASE-A-MONTH, 2012, 58 (04) :219-238
[6]   A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cells [J].
De Marchis, M. L. ;
Ballarino, M. ;
Salvatori, B. ;
Puzzolo, M. C. ;
Bozzoni, I. ;
Fatica, A. .
LEUKEMIA, 2009, 23 (05) :856-862
[7]   Differentiation therapy revisited [J].
de The, Hugues .
NATURE REVIEWS CANCER, 2018, 18 (02) :117-127
[8]   Acute Myeloid Leukemia [J].
Doehner, Hartmut ;
Weisdorf, Daniel J. ;
Bloomfield, Clara D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (12) :1136-1152
[9]   Acute myeloid leukaemia [J].
Estey, Elihu ;
Doehner, Hartmut .
LANCET, 2006, 368 (9550) :1894-1907
[10]  
FERRERO D, 1983, BLOOD, V61, P171