A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia

Acute erythroleukemia is a rare form of acute myeloid leukemia recognized by its distinct phenotypic attribute erythroblasts proliferation. In this study, in vitro experiments showed that newly synthesized chalcone (ZH-254) inhibited cell proliferation, caused apoptosis, arrested the cycle G1 phase, and downregulated Fli-1 expression inhibiting promoter activity. vivo ZH-254 could effectively alleviate splenomegaly prolong survival mice. RT-PCR Western blot analysis regulate target genes G1-phase-related proteins, including Rb, Bcl-2, Bax, ERK1/2, Gata-1, P110, SHIP-1, p-ERK1, CDK4, C-myc, Cyclin D1, Smad-3, GSK-3, p21. Among them, compound most significantly regulated phosphorylation ERK1, gene involved regulating proliferation apoptosis. Thus, restricts malignancy causing inactivation via suppressing activity, further ERK1- genes. These results reveal critical role growth various hematological malignancies point to derivatives as lead compounds for development anti-Fli-1 drugs treatment with overexpression Fli-1.