Glycine N-methyltransferase (GNMT) expression is vastly downregulated in
hepatocellular carcinomas (HCC). High rates of GNMT knockout mice developed HCC, while overexpression of GNMT prevented
aflatoxin-induced carcinogenicity and inhibited
liver cancer cell proliferation. Therefore, in this study, we aimed for the identification of a GNMT inducer for HCC
therapy. We established a GNMT promoter-driven
luciferase reporter assay as a
drug screening platform. Screening of 324 pure compounds and 480
crude extracts from Chinese medicinal herbs resulted in the identification of Paeonia lactiflora Pall (PL) extract and the active component 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (
PGG) as a GNMT inducer. Purified PL extract and
PGG induced GNMT
mRNA and
protein expression in Huh7 human
hepatoma cells and in xenograft
tumors.
PGG and PL extract had potent anti-HCC effects both in vitro and in vivo. Furthermore,
PGG treatment induced apoptosis in Huh7 cells. Moreover,
PGG treatment sensitized Huh7 cells to
sorafenib treatment. Therefore, these results indicated that identifying a GNMT enhancer using the GNMT promoter-based assay might be a useful approach to find drugs for HCC. These data also suggested that
PGG has therapeutic potential for the treatment of HCC.