18α-Glycyrrhetinic acid induces apoptosis in gingival fibroblasts derived from gingival overgrowth caused by nifedipine in a patient

Abstract

We have previously suggested that the population of nifedipine-sensitive fibroblasts in nifedipine responder cells (NIFr cells) obtained from hyperplastic gingival tissue of nifedipine-reactive patients was greater than that in nifedipine non-responder cells (NIFn cells) obtained from non-hyperplastic gingival tissue of nifedipine-nonreactive patients. It has also been reported that 18α-glycyrrhetinic acid (18α-GA) significantly induced apoptosis in human cancer cells whose replication rate was slow, by inhibiting the onset of progression. In this study, we focused on how 18α-GA affects apoptosis in NIFr cells and decreases their number. Semi-confluent cells were arrested in DMEM substituted by 0.5% FBS for 24 h, stimulated by various concentrations of 18α-GA, and then apoptosis assay, flow cytometry analysis, and RT-PCR analysis were performed. Apoptosis assay and flow cytometry analysis showed that 18α-GA increased the number of cells that underwent apoptosis and decreased G₀/G₁ phase cells in NIFr. The mRNA expression of bcl-2, the suppressor for apoptosis, was suppressed by 18α-GA in NIFr cells; however, the mRNA expression of p53 was not changed. Since 18α-GA induces apoptosis though suppressing mRNA expression of bcl-2 in NIFr cells, it might be useful for reducing gingival fibroblasts and thus reducing gingival overgrowth caused by nifedipine.