The Involvement of Canonical NFκB Pathway in Megakaryocyte Differentiation Induction by Nanocurcumin

Background: 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. Materials and Methods: 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 c-MYC, BAX, and NQO1 was also analyzed in nanocurcumin-treated K562 cells by quantitative RT-PCR assay at different times. Results: The study has shown that nanocurcumin causes an increase in NFκB activity transiently during megakaryocyte differentiation, followed by a change in the expression of c-MYC, BAX, and NQO1 target genes. Conclusion: The NFκB pathway can be considered a new pathway for inducing megakaryocyte differentiation by nanocurcumin in vitro and in vivo megakaryopoiesis experiments.