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Planta Med 2014; 80(05): 399-408
DOI: 10.1055/s-0034-1368183
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Matrine Cooperates with All-Trans Retinoic Acid on Differentiation Induction of All-Trans Retinoic Acid-Resistant Acute Promyelocytic Leukemia Cells (NB4-LR1): Possible Mechanisms

Dijiong Wu   *
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
Keding Shao   *
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
Jie Sun
2   Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China
,
Fuyun Zhu
3   Zhejiang University of Traditional Chinese Medicine, Hangzhou, China
,
Baodong Ye
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
Tingting Liu
2   Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China
,
Yiping Shen
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
He Huang
2   Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China
,
Yuhong Zhou
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
› Author Affiliations
Further Information

Publication History

received 11 August 2013
revised 16 January 2014

accepted 29 January 2014

Publication Date:
11 March 2014 (online)

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Abstract

Retinoic acid resistance results in refractory disease, and recovery in acute promyelocytic leukemia remains a challenge in clinical practice, with no ideal chemotherapeutic drug currently available. Here we report on the effect of an active compound of Sophora flavescens called matrine (0.1 mmol/L) combined with all-trans retinoic acid (1 µmol/L) in alleviating retinoic acid resistance in acute promyelocytic leukemia-derived NB4-LR1 cells by differentiation induction, as can be seen by an induced morphology change, increased CD11b expression, and nitro blue tetrazolium reduction activity, and a decreased expression of the promyelocytic leukemia-retinoic acid receptor α fusion gene and protein product. We further explored the probable mechanism of how matrine promotes the recovery of differentiation ability in NB4-LR1 cells when exposed to all-trans retinoic acid. We observed that the combination of all-trans retinoic acid and matrine can increase the level of cyclic adenosine monophosphate and protein kinase A activity, reduce telomerase activity, and downregulate the protein expression of topoisomerase II beta in NB4-LR1 cells. The results of this study suggest the possible clinical utility of matrine in the treatment of retinoic acid-resistant acute promyelocytic leukemia.

Key words

matrine - retinoic acid-resistant - acute promyelocytic leukemia - all-trans retinoic acid - cellular differentiation - Sophora flavescens - Fabaceae

* Both of these authors contributed equally to this study.


Supporting Information

 

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