Artesunate Induces SKM-1 Cells Apoptosis by Inhibiting Hyperactive β-catenin Signaling Pathway.

Artesunate Induces SKM-1 Cells Apoptosis by Inhibiting Hyperactive β-catenin Signaling Pathway.
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DOI:
10.7150/ijms.11352
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发表时间:
2015
影响因子:
3.6
通讯作者:
Liu XL
Liu XL
中科院分区:
医学4区
文献类型:
--
作者:
Xu N;Zhou X;Wang S;Xu LL;Zhou HS;Liu XL

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前言:青蒿琥酯(Artesunate,ART)是一种在世界各地广泛使用的治疗严重疟疾的药物,也具有抑制不同类型肿瘤生长的能力。然而,确切的分子机制仍不清楚。方法:采用骨髓增生异常综合征(MDS)细胞(SKM-1细胞)经不同浓度的ART作用于多个时间点,观察后续细胞功能的变化及可能涉及的通路基因。结果:我们发现ART具有抑制SKM-1细胞增殖和诱导细胞凋亡的作用,且呈剂量和时间依赖性。去甲基酶恢复的CDH1基因表达可能参与了细胞凋亡过程。β-连环蛋白从胞核和胞浆转位到细胞膜,导致β-连环蛋白信号通路失活。结论:我们的研究结果为开发ART作为治疗骨髓增生异常综合征的有效药物提供了合理的依据。
Introduction: Artesunate (ART), a wildly used agent to treat severe malarial around the world, also has the power to inhibit growth of different types of tumor. However, the exact molecular mechanisms keep unknown. Method: In this study, we used myelodysplastic syndrome (MDS) cells (SKM-1 cells) with differential ART concentrations treatment at multiple time points to observe the subsequence cell function alteration and the possible involved pathway genes. Results: We found that ART demonstrated the ability to inhibit proliferation and induce apoptosis in SKM-1 in a dose and time-dependent manner. Demethylase recovered CDH1 gene expression may be involved in the apoptosis process. The β-catenin protein translocated from the nucleus and cytoplasm to the membrane result in inactivation of β-catenin signaling pathway. Conclusion: Our findings provide a rational basis to develop ART as a useful therapeutic agent for the treatment of myelodysplastic syndromes.
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