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

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.

Automated summary

MQ-16 shows significant inhibitory effects on the proliferation of K562 cells and induces cell cycle arrest at the G2/M phase in a time- and concentration-dependent manner. It induces mitochondria-dependent apoptosis by downregulating anti-apoptotic proteins Bcl-2 and Bcl-xL, and causes time- and concentration-dependent DNA fragmentation. Furthermore, MQ-16 affects the expression of PI3K/Akt/mTOR, JAK2/STAT3, and MAPK pathway-related proteins.