Mortazavi Farsani Seyedeh Sahar, Sadeghizadeh Dina, Babashah Sadegh, Rad Fariba, Sadeghizadeh Majid
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
Int J Hematol Oncol Stem Cell Res. 2023 Jan 1;17(1):18-27. doi: 10.18502/ijhoscr.v17i1.11709.
Megakaryopoiesis is characterized by progressive polyploidization and the expression of megakaryocytic markers. Numerous transcription factors and physiological signaling pathways regulate this phenomenon. Megakaryocyte differentiation induction in the K562 cell line and hematopoietic stem cells via nanocurcumin drug has been identified in our previous study. K562 cells are typical Chronic Myelogenous Leukemia (CML) cells that are resistant to apoptosis and express the bcr-abl fusion gene. These cells have the potential to differentiate into erythrocytes and megakaryocytes. Curcumin is well known as a component with strong potential to alter NFκB activity in various cells. NFκB pathway regulates various genes such as apoptotic and immune response genes. The current study attempted to evaluate the possible role of nanocurcumin in NFκB pathway regulation during the megakaryopoiesis process in the K562 cell line. Megakaryocyte markers expression and phenotype alteration of nanocurcumin-treated K562 cells have been detected by flow cytometry and microscopy imaging. The nuclear level of the RelA (p65) subunit of NFκB was determined by western blot test in K562 cells during megakaryopoiesis induction via nanocurcumin treatment at different times. The expression of NFκB target genes including , , was also analyzed in nanocurcumin-treated K562 cells by quantitative RT-PCR assay at different times. The study has shown that nanocurcumin causes an increase in NFκB activity transiently during megakaryocyte differentiation, followed by a change in the expression of , , target genes. The NFκB pathway can be considered a new pathway for inducing megakaryocyte differentiation by nanocurcumin in vitro and in vivo megakaryopoiesis experiments.
巨核细胞生成的特征是进行性多倍体化和巨核细胞标志物的表达。众多转录因子和生理信号通路调节这一现象。在我们之前的研究中，已确定通过纳米姜黄素药物在K562细胞系和造血干细胞中诱导巨核细胞分化。K562细胞是典型的慢性粒细胞白血病（CML）细胞，对凋亡具有抗性并表达bcr-abl融合基因。这些细胞有分化为红细胞和巨核细胞的潜力。姜黄素是一种众所周知的在各种细胞中具有强大潜力改变NFκB活性的成分。NFκB通路调节各种基因，如凋亡和免疫反应基因。当前研究试图评估纳米姜黄素在K562细胞系巨核细胞生成过程中对NFκB通路调节的可能作用。已通过流式细胞术和显微镜成像检测了纳米姜黄素处理的K562细胞的巨核细胞标志物表达和表型改变。在通过纳米姜黄素处理在不同时间诱导巨核细胞生成的过程中，通过蛋白质免疫印迹试验在K562细胞中测定了NFκB的RelA（p65）亚基的核水平。在不同时间通过定量逆转录聚合酶链反应分析了纳米姜黄素处理的K562细胞中包括 、 、 在内的NFκB靶基因的表达。该研究表明，纳米姜黄素在巨核细胞分化过程中短暂导致NFκB活性增加，随后 、 、 靶基因的表达发生变化。在体外和体内巨核细胞生成实验中，NFκB通路可被视为纳米姜黄素诱导巨核细胞分化的新途径。
