[Epigallocatechin gallate induces CHD5 gene demethylation to promote acute myeloid leukemia cell apoptosis in vitro by regulating p19Arf-p53-p21Cip1 signaling pathway].

ABSTRACT: OBJECTIVE:To investigate the mechanism by which epigallocatechin gallate (EGCG) induces CHD5 gene demethylation and promotes the apoptosis of acute myeloid leukemia KG-1 and THP-1 cell lines. METHODS:KG-1 and THP-1 cells treated with 25, 50, 75, 100 or 150 ?g/mL EGCG for 48 h were examined for CHD5 gene methylation using MSP and for cell proliferation using MTT assay. The changes in cell cycle and apoptosis of the two cell lines after treatment with EGCG for 48 h were detected using flow cytometry. The mRNA and protein expressions of DNMT1, CHD5, p19Arf, p53 and p21Cip1 in the cells were detected using RT-quantitative PCR and Western blot. RESULTS:EGCG dose-dependently reversed hypermethylation of CHD5 gene and reduced the cell viability in both KG-1 and THP-1 cells (P < 0.05). EGCG treatment caused obvious cell cycle arrest in G1 phase, significantly increased cell apoptosis, downregulated the expression of DNMT1 and upregulated the expressions of CHD5, p19Arf, p53 and p21Cip1 in KG-1 and THP-1 cells (P < 0.05). CONCLUSIONS:EGCG reduces hypermethylation of CHD5 gene in KG-1 and THP-1 cells by downregulating DNMT1 to restore its expression, which results in upregulated expressions of p19Arf, p53 and p21Cip1 and induces cell apoptosis.

SUBMITTER: Wu M 

PROVIDER: S-EPMC7544577 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature