Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells
Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells
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DOI：
10.1016/j.ejphar.2014.10.064
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发表时间：
2015-01-15
影响因子：
5
通讯作者：
Kim, Hawk
中科院分区：
文献类型：
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作者：
Heo, Sook-Kyoung;Noh, Eui-Kyu;Kim, Hawk
迷迭香酸（Rosmarinic acid，RA）是咖啡酸和3，4-二羟基苯乳酸的酯，具有多种生物活性，但其与全反式维甲酸（alltransretinoic acid，ATRA）联合应用对急性早幼粒细胞白血病（acute promyelocytic leukemia，APL）细胞的抗白血病作用尚不清楚。应用流式细胞术检测了APL患者骨髓细胞（BMC）、NB 4细胞（APL细胞系）、正常BMC和健康受试者外周血单个核细胞（PBMC）中的分化标志物CD 11b。ATRA/RA诱导APE患者BMC和NB 4细胞中CD 11b表达，但不诱导正常BMC或PBMC中CD 11b表达。因此，我们认识到，RA增强ATRA诱导的APL细胞的巨噬细胞分化。诱导的巨噬细胞的进一步表征表明，它们表现出形态学变化，并能够吞噬和产生活性氧。C-C趋化因子受体1（CCR 1）、CCR 2和细胞间粘附分子1（ICAM-1）的表达也较典型。CD 11 B（+）和CD 14（+）细胞的表达依赖于MK-NE-kappa B轴的激活。总之，这些结果表明，RA增强ATRA诱导的APL细胞中的巨噬细胞分化。因此，RA可能作为APL中功能性巨噬细胞分化的辅助分化剂发挥重要作用。此外，分化的巨噬细胞可能具有正常的寿命，并且它们可能死亡。这些数据表明，联合治疗RA和ATRA有潜力作为APL的抗白血病治疗。(C)2014爱思唯尔有限公司版权所有。
Rosmarinic acid (RA, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid) has a number of biological activities, but little is known about anti-leukemic activities of RA combined with all trans retinoic acid (ATRA) against acute promyelocytic leukemia (APL) cells. We examined the differentiation marker, CD11b, in bone marrow cells (BMC) of an APL patient, in NB4 cells (APL cell line), and in normal BMC and peripheral blood mononuclear cells (PBMC) of healthy subjects by flow cytometric analysis. ATRA/RA induced expression of CD11b in the BMC of the APE patient and in NB4 cells, but not in normal BMC or PBMC. Therefore, we realized that RA potentiated ATRA-induced macrophage differentiation in APL cells. Further characterization of the induced macrophages showed that they exhibited morphological changes and were able to phagocytose and generate reactive oxygen species. Th also had typical expression of C-C chemokine receptor type 1 (CCR1), CCR2, and intercellular adhesion molecule-1 (ICAM-1). Moreover, the expression of CD11b(+) and CD14(+) cells depended on MK-NE-kappa B axis activation. Together, these results indicate that RA potentiates ATRA-induced macrophage differentiation in APL cells. Thus, RA may play an important role as an appurtenant differentiation agent for functional macrophage differentiation in APL. Additionally, the differentiated macrophages might have a normal life span and, they could die. These data indicate that co-treatment with RA and ATRA has potential as an anti-leukemic therapy in APL. (C) 2014 Elsevier B.V. All rights reserved.