Parthenolide induces promoter hypomethylation methylation-silenced genes
and their re-expression. A, perturbation of HIN-1 promoter methylation in
MCF-7 cells exposed to indicated concentrations of parthenolide. DNA (1 μg)
from parthenolide-treated or untreated MCF-7 cells were treated with bisulfite
followed by PCR amplification, M.SssI methylation, and digestion to
nucleosides. 5mdC and 2dC in the hydrolysates were measured using the LC-MS/MS
method, and the ratio of 5mdC to 2dC is used as a DNA methylation indicator.
B, hypomethylation activities of parthenolide (10 and 30 μM) and decitabine
(0.75 μM) on HIN-1 promoter detected by bisulfite-sequencing. A 15%
decrease of the promoter methylation in parthenolide-treated group was found.
The solid circles represent methylated CpG loci, and the open circles
represent nonmethylated CpG loci. C, parthenolide increased expression of
HIN-1 gene in MCF-7 cells treated with parthenolide for the indicated time
points and dosages. HIN-1 gene expression was measured by real-time RT-PCR.
Conc, untreated; DAC, decitabine (0.75 μM); Par, parthenolide.