Icariside II induces cell cycle arrest and differentiation via TLR8/MyD88/p38 pathway in acute myeloid leukemia cells
Icariside II induces cell cycle arrest and differentiation via TLR8/MyD88/p38 pathway in acute myeloid leukemia cells
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Icariside II 通过 TLR8/MyD88/p38 通路诱导急性髓系白血病细胞的细胞周期停滞和分化
DOI：
10.1016/j.ejphar.2018.12.026
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发表时间：
2019-03
影响因子：
5
通讯作者：
Zhang Tong
中科院分区：
文献类型：
--
作者：
Yang Jing;Lan Jinshuai;Du Hongzhi;Zhang Xiaoling;Li Aiyun;Zhang Xinyu;Liu Yun;Zhang Jieyi;Zhang Chaochao;Ding Yue;Zhang Tong
急性髓性白血病（AML）是一种毁灭性的血液恶性肿瘤，其特征是髓系未成熟细胞的分化停滞和非程序性增殖。诱导AML细胞分化已成为治疗AML的有前途的治疗策略。淫羊藿苷II是淫羊藿中的一种有效成分，具有促进成骨分化的作用。然而，淫羊藿苷II对AML细胞的分化诱导作用尚未被探索。本研究探讨了淫羊藿苷Ⅱ对急性髓性白血病HL-60和THP-1细胞的诱导分化作用及其机制。淫羊藿苷II通过下调细胞周期蛋白依赖性激酶（CDK 2、CDK 4和CDK 6）和上调细胞周期蛋白依赖性激酶抑制剂（p21和p27）诱导细胞周期阻滞于G1期。重要的是，淫羊藿苷II可以诱导AML细胞分化，伴随着Toll样受体8（TLR 8）、髓样分化因子88（MyD 88）和磷酸化p38的上调。进一步的研究表明，TLR 8特异性抑制剂CU-CPT 9a可阻断淫羊藿苷II诱导的细胞周期阻滞和分化。总而言之，这些发现首次证明了淫羊藿苷II通过激活TLR 8/MyD 88/p38途径诱导AML细胞的细胞周期停滞和分化，表明淫羊藿苷II可以开发成为一种新型的AML分化诱导剂。
Acute myeloid leukemia (AML) is a devastating hematological malignancy, characterized by differentiation arrest and unscheduled proliferation of immature cells of the myeloid lineage. Inducing AML cell differentiation has emerged as a promising therapeutic strategy for the therapy of AML. Icariside II, an active component ofHerba Epimedii, has been well defined to promote osteogenic differentiation. However, the differentiation-inducing effect of Icariside II on AML cells has not been explored. In this study, we investigated the differentiation-inducing effect and underlying mechanism of Icariside II in AML HL-60 and THP-1 cell lines. Icariside II induced G1 phase cell cycle arrest by down-regulating Cyclin-dependent kinases (CDK2, CDK4 and CDK6) and up-regulating Cyclin-dependent kinase inhibitor (p21 and p27). Importantly, Icariside II could induce differentiation of AML cells, accompanied by the up-regulation of Toll-like receptor 8 (TLR8), myeloid differentiation factor 88 (MyD88) and phosphorylated p38. Further study indicated the cell cycle arrest and differentiation induced by Icariside II could be abrogated by TLR8-specific inhibitor CU-CPT9a. Collectively, these findings firstly demonstrate Icariside II induces cell cycle arrest and differentiation of AML cells via activation of TLR8/MyD88/p38 pathway, suggesting Icariside II could be developed into a novel differentiation-inducing agent for AML.
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影响因子：
9.7
作者：
Lee, Keun-Sung;Lee, Hyo-Jeong;Kim, Sung-Hoon
通讯作者：
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影响因子：
14.8
作者：
Zhang S;Hu Z;Tanji H;Jiang S;Das N;Li J;Sakaniwa K;Jin J;Bian Y;Ohto U;Shimizu T;Yin H
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影响因子：
2.2
作者：
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Guangming Luo;Biao Xu;Yuanliang Huang
影响因子：
50.3
作者：
D. Altieri
通讯作者：
D. Altieri
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影响因子：
11.2
作者：
Ramachandran V;Arumugam T;Wang H;Logsdon CD
通讯作者：
Logsdon CD