岩藻黄质通过AKT/mTOR途径调节糖酵解代谢促进人急性淋巴细胞白血病细胞凋亡的作用研究OA北大核心CSTPCD

To elucidate the mechanism by which fucoxanthin promotes the apoptosis in human acute lymphoblastic leukemia(CEM/C1)cells,the following experimental approaches were employed.Cell viability of CEM/C1 cells after fucoxanthin treatment was assessed using the MTT assay.Early and late apoptosis rates,as well as cell cycle distribution of CEM/C1 cells,were determined using flow cytometry.Fucoxanthin's impact on pyruvate kinase(PK)and hexokinase(HK)activity,glucose uptake,adenosine triphosphate(ATP)production,and lactate production in CEM/C1 cells was measured using assay kits.The expression levels of relevant proteins in CEM/C1 cells were assessed through Western blot analysis.Molecular docking was performed to validate the interactions.Results indicated that fucoxanthin significantly inhibited the viability of CEM/C1 cells in a dose-and time-dependent manner.With increasing fucoxanthin concentration,the early and late apoptosis rates of CEM/C1 cells increased,accompanied by a significant or extremely significant decrease in the proportion of cells in the G1/G2 phase and significant or extremely significant increase in the proportion of cells in the S phase.Fucoxanthin markedly inhibited the activity and expression levels of glycolytic enzymes(PK,HK),and also reduced the expression levels of phosphorylated mTOR and phosphorylated AKT proteins.Molecular docking analysis revealed that the binding energy between fucoxanthin and AKT and mTOR proteins was less than-5 kcal·mol-1,primarily through hydrogen bonding at the enzyme's active site.In conclusion,fucoxanthin significantly promoted the apoptosis in CEM/C1 cells,and its mechanism of action may be associated with the regulation of glycolysis through the AKT/mTOR signal pathway.These findings provide a theoretical basis for the development of high-value-added products from Sargassum fusiforme and the screening of natural,safe anti-leukemia drug precursors.