Li Peng, Yan Shuxin, Dong Xin, Li Zhao, Qiu Yu, Ji Chunyan, Zhang Jingru, Ji Min, Li Wei, Wang Hongchun, Liu Zhi, Wang Xing L, Ye Jingjing, Ma Daoxin
Department of Hematology, Qilu Hospital, Shandong University, Jinan. China.
Department of Hematology, Qilu Hospital (Qingdao), Shandong University, Qingdao. China.
Med Chem. 2018;14(1):60-66. doi: 10.2174/1573406413666170620091543.
Acute myeloid leukemia (AML) is the most common hematological malignancy in adults, characterized by distorted proliferation and development of myeloid cells and their precursors in the bone marrow. Nitidine chloride, a naturally occurring alkaloid, has been identified to possess antitumor activity. However, the effects of nitidine chloride on acute myeloid leukemia cells and its underlying mechanisms have not been elucidated. Here we investigated the cellular and molecular mechanism of the anti-leukemic effects of nitidine chloride.
Nitidine chloride treatment for 48 consecutive hours exhibited a timedependent and dose-dependent growth inhibition activity against AML cells by inducing cell cycle arrest and apoptosis. Moreover, nitidine chloride downregulated Cyclin B1, CDK1 and Bcl-2, upregulated p27 and Bax, inactivated PARP, activated Caspase-3 in AML cells. We further demonstrated that growth inhibition activity of nitidine chloride in AML cells is partially via inhibiting the phosphorylation of AKT and ERK.
In conclusion, our data suggest that nitidine chloride could be an effective therapeutic agent against AML via cell cycle arrest and apoptosis.
急性髓系白血病（AML）是成人中最常见的血液系统恶性肿瘤，其特征是骨髓中髓系细胞及其前体细胞的增殖和发育异常。氯化两面针碱是一种天然生物碱，已被证实具有抗肿瘤活性。然而，氯化两面针碱对急性髓系白血病细胞的作用及其潜在机制尚未阐明。在此，我们研究了氯化两面针碱抗白血病作用的细胞和分子机制。
连续48小时用氯化两面针碱处理对AML细胞具有时间和剂量依赖性的生长抑制活性，可诱导细胞周期阻滞和凋亡。此外，氯化两面针碱下调AML细胞中的细胞周期蛋白B1、周期蛋白依赖性激酶1（CDK1）和Bcl-2，上调p27和Bax，使聚（ADP-核糖）聚合酶（PARP）失活，激活半胱天冬酶-3。我们进一步证明，氯化两面针碱在AML细胞中的生长抑制活性部分是通过抑制AKT和ERK的磷酸化实现的。
总之，我们的数据表明，氯化两面针碱可能是一种通过细胞周期阻滞和凋亡有效治疗AML的药物。
