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The Flavagline Compound 1-(2-(dimethylamino)acetyl)-Rocaglaol Induces Apoptosis in K562 Cells by Regulating the PI3K/Akt/mTOR, JAK2/STAT3, and MAPK Pathways
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2022-08-04 , DOI: 10.2147/dddt.s357891
Xinmei Yang 1, 2, 3 , Xijun Wu 4 , Xiaosen Wu 5 , Lei Huang 1, 2 , Jingrui Song 1, 2 , Chunmao Yuan 1, 2 , Zhixu He 3, 6 , Yanmei Li 1, 2
Affiliation  

Purpose: Chronic myelogenous leukemia (CML) is a hematological malignancy with increased proliferation of cells of the myeloid series. This can disrupt normal hematopoiesis. The 1-(2-(dimethylamino)acetyl)-rocaglaol (MQ-16) is a new synthetic flavagline compound that showed promising activity in chronic myeloid leukemia K562 cells. This study aims to analyze the underlying mechanisms of MQ-16 against CML.
Methods: Growth, cell cycle progression, and apoptosis were assessed in K562 cells following MQ-16 exposure by MTT assay and flow cytometry. The effect of MQ-16 on DNA strands between nucleosomes was examined by 1% agarose gel electrophoresis. PI3K/Akt/mTOR, JAK2/STAT3, and mitogen-activated protein kinase (MAPK) pathway-related proteins were detected in MQ-16–treated K562 cells by Western blot.
Results: MQ-16 significantly inhibited the proliferation of K562 cells and arrested the cell cycle at the G2/M phase in a time- and concentration-dependent manner. MQ-16 induced mitochondria-dependent apoptosis by downregulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and induced time- and concentration-dependent DNA fragmentation. In addition, MQ-16 affected the expression of PI3K/Akt/mTOR, JAK2/STAT3, and MAPK pathway-related proteins.
Conclusion: In summary, MQ-16 appears to be a promising chemotherapeutic drug for treating CML.

Keywords: CML, flavagline, cycle arrest, apoptosis, PI3K/Akt/mTOR, JAK2/STAT3, MAPK


中文翻译:

Flavagline 化合物 1-(2-(二甲基氨基)乙酰基)-Rocaglaol 通过调节 PI3K/Akt/mTOR、JAK2/STAT3 和 MAPK 通路诱导 K562 细胞凋亡

目的:慢性粒细胞性白血病 (CML) 是一种血液恶性肿瘤,髓系细胞增殖增加。这会破坏正常的造血功能。1-(2-(二甲基氨基)乙酰基)-罗卡劳醇 (MQ-16) 是一种新的合成黄素化合物,在慢性髓性白血病 K562 细胞中显示出良好的活性。本研究旨在分析 MQ-16 对抗 CML 的潜在机制。
方法:通过 MTT 测定和流式细胞术评估 MQ-16 暴露后 K562 细胞的生长、细胞周期进程和凋亡。通过 1% 琼脂糖凝胶电泳检测 MQ-16 对核小体之间 DNA 链的影响。通过蛋白质印迹在 MQ-16 处理的 K562 细胞中检测到 PI3K/Akt/mTOR、JAK2/STAT3 和丝裂原活化蛋白激酶 (MAPK) 通路相关蛋白。
结果: MQ-16显着抑制K562细胞增殖,使细胞周期停滞在G2/M期,呈时间和浓度依赖性。MQ-16 通过下调抗凋亡蛋白 Bcl-2 和 Bcl-xL 诱导线粒体依赖性细胞凋亡,并诱导时间和浓度依赖性 DNA 片段化。此外,MQ-16 影响 PI3K/Akt/mTOR、JAK2/STAT3 和 MAPK 通路相关蛋白的表达。
结论:综上所述,MQ-16 似乎是一种有前途的治疗 CML 的化疗药物。

关键词: CML,黄曲霉素,周期阻滞,细胞凋亡,PI3K/Akt/mTOR,JAK2/STAT3,MAPK
更新日期:2022-08-04
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