Journal
PLANTA MEDICA
Volume 80, Issue 5, Pages 399-408Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0034-1368183
Keywords
matrine; retinoic acid-resistant; acute promyelocytic leukemia; all-trans retinoic acid; cellular differentiation; Sophora flavescens; Fabaceae
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Funding
- Natural Science Foundation of Zhejiang Province [Y2101416]
- Scientific Research Fund of Zhejiang Provincial Education Department [Y201223638]
- Zhejiang Outstanding Young Talent Fund of Traditional Chinese Medicine [2013ZQ012]
- National Natural Science Fund [30600256]
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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 (0.1mmol/L) combined with all-trans retinoic acid (1 mu mol/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 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.
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