Objective        To determine the effects of dihydromyricetin on methylation status and expression of phosphatase and tensin homology deleted on chromosome ten (PTEN) gene in human MCF-7 breast cancer cells and explore the relevant mechanisms.       Methods        Cells viability was assessed by CCK-8 assay in MCF-7 cells after the treatment of dihydromyricetin at 10

20

40 and 80 μmol/L for 48 h. The expression of DNA methyltransferases (DNMT

including DNMT1

DNMT3a

and DNMT3b) and PTEN was measured by quantitative real-time PCR and Western blotting. DNMT activity was detected by DNMT activity/inhibition assay kit (fluorometrics). Modified methylation specific PCR (MSP) was used to screen the methylation level of PTEN.       Results        Dihydromyricetin significantly decreased the viability of MCF-7 cells in a dose-dependent manner. The qRT-PCR analysis and Western blotting showed that dihydromyricetin dose-dependently increased the expression of PTEN in MCF-7 cells. MSP showed that dihydromyricetin markedly induced PTEN demethylation in MCF-7 cells. Further studies indicated that dihydromyricetin decreased the expression of DNMT1 and inhibited the activity of DNMT.       Conclusion        Dihydromyricetin significantly induces PTEN demethylation and promotes its expression in breast cancer MCF-7 cells

and this effect may be mainly correlated with inhibition of DNMT1 expression and activity.