title: Matrine cooperates with all-trans retinoic acid on differentiation induction of all-trans retinoic acid-resistant acute promyelocytic leukemia cells (NB4-LR1): possible mechanisms.
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.
authors.affiliation: Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Dijiong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Keding
authors.initials: K
authors.lastname: Shao
authors.affiliation: Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Zhejiang University of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Fuyun
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Baodong
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004357:Drug Synergism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011807:Quinolizines / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D017931:DNA Primers; D011807:Quinolizines; D014212:Tretinoin; D000093842:Matrines