Berberine inhibited arylamine N-acetyltransferase activity and gene expression and DNA adduct formation in human malignant astrocytoma (G9T/VGH) and brain glioblastoma multiforms (GBM 8401) cells.
Studies have demonstrated that berberine exhibits the antineoplastic action in rat model. Rat glial tumor cells also have been shown to have N-acetyltransferase activity. In this study, we reported the effects of berberine on arylamine N-acetyltransferase (NAT) activity, gene expression, and DNA adduct formation in human brain tumor cell lines (G95/VGH and GBM 8401). The activity of NAT (N-acetylation of substrate) was measured and determined by high-performance liquid chromatography (HPLC) assaying for the amounts of acetylated 2-aminofluorene (AF) and nonacetylated AF. Human brain tumor cells (G9T/VGH and GBM 8401) were used for examining NAT activity and gene expression and AF-DNA adduct formation. NAT gene expression was determined by polymerase chain reaction (PCR) for the levels of mRNA NAT in both examined cells lines. The amounts of AF-DNA adducts were also determined and quantities by HPLC. The results demonstrated that NAT activity, levels of mRNA NAT1 and AF-DNA adduct formation in both examined cell were inhibited and decreased by berberine in a dose-dependent manner. The apparent values of Km and Vmax from NAT of both examined cells were also determined with or without berberine cotreatment. The data also indicated that berberine decreased the apparent values of Km and Vmax. These effects also indicate that berberine is a uncompetitive inhibitor.
Wang
D Y
DY
Department of Orthopaedics, China Medical College Hospital, Taichung, Taiwan, People's Republic of China.
Yeh
C C
CC
Lee
J H
JH
Hung
C F
CF
Chung
J G
JG
D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D001599:Berberine / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018736:DNA Adducts / Q000096:biosynthesis*; D017931:DNA Primers; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D014407:Tumor Cells, Cultured
D018736:DNA Adducts; D017931:DNA Primers; D001599:Berberine; D001191:Arylamine N-Acetyltransferase