Involvement of C/EBPβ in monocytic differentiation of acute myeloid leukemia cells induced by LW-218, a new synthesized flavonoid.

In this study, we found that LW-218, a new synthesized flavonoid, inhibited proliferation and induced differentiation of acute myeloid leukemia cells. The IC50s of LW-218 in HL-60, U937, K562, and NB4 cell lines were all less than 5 μM, suggesting greater capacity than compounds we have reported. LW-218 induced differentiation effects including morphologic changes, NBT reduction, and both of CD11b and CD14 expression. Results of western blots and siRNA transfection revealed that LW-218 increased the LAP/LIP ratio of C/EBPβ which regulated monocytic differentiation of leukemia cells. Meanwhile, these differentiation effects could be attenuated by silencing PLSCR1 via siRNA transfection. In addition, regulation on LAP/LIP ratio, of C/EBPβ was properly mediated by PLSCR1 which was up-regulated by LW-218. All these results suggested that C/EBPβ was involved in regulation of PKCδ/PLSCR1 pathway during flavonoids-induced differentiation. LW-218 was a prospective differentiation inductor of AML cells and was requisite to proceed further investigation. Keywords: flavonoid, acute myeloid leukemia, differentiation, PLSCR1, C/EBPβ PMID: 25150309 [PubMed - as supplied by publisher]
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research