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

The Flavagline Compound 1-(2-(dimethylamino)acetyl)-Rocaglaol Induces Apoptosis in K562 Cells by Regulating the PI3K/Akt/mTOR, JAK2/STAT3, and MAPK Pathways.

机构信息

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, People's Republic of China.

The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guizhou Medical University, Guiyang, 550014, People's Republic of China.

出版信息

Drug Des Devel Ther. 2022 Aug 4;16:2545-2557. doi: 10.2147/DDDT.S357891. eCollection 2022.

DOI:10.2147/DDDT.S357891
PMID:35959422
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9359389/
Abstract

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.

摘要

目的

慢性髓系白血病（CML）是一种髓系细胞增殖增多的血液系统恶性肿瘤。这会扰乱正常的造血。1-(2-(二甲基氨基)乙酰基)-rocaglaol（MQ-16）是一种新的合成 flavagline 化合物，在慢性髓系白血病 K562 细胞中表现出有希望的活性。本研究旨在分析 MQ-16 对抗 CML 的潜在机制。

方法

通过 MTT 法和流式细胞术评估 K562 细胞在 MQ-16 暴露后细胞的生长、细胞周期进展和凋亡情况。通过 1%琼脂糖凝胶电泳检查 MQ-16 对核小体间 DNA 链的影响。通过 Western blot 检测 MQ-16 处理的 K562 细胞中 PI3K/Akt/mTOR、JAK2/STAT3 和丝裂原活化蛋白激酶（MAPK）途径相关蛋白。

结果

MQ-16 显著抑制 K562 细胞的增殖，并以时间和浓度依赖的方式将细胞周期阻滞在 G2/M 期。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 途径相关蛋白的表达。

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/c545053e47e1/DDDT-16-2545-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/f7d07b748b8c/DDDT-16-2545-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/db6843939a4b/DDDT-16-2545-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/d814a406fe81/DDDT-16-2545-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/11ebfa7cd899/DDDT-16-2545-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/4eb033087d4f/DDDT-16-2545-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/c545053e47e1/DDDT-16-2545-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/f7d07b748b8c/DDDT-16-2545-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/db6843939a4b/DDDT-16-2545-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/d814a406fe81/DDDT-16-2545-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/11ebfa7cd899/DDDT-16-2545-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/4eb033087d4f/DDDT-16-2545-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd89/9359389/c545053e47e1/DDDT-16-2545-g0006.jpg

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