Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth

Background and PurposeThis investigation aimed to establish the basis of a pharmacotherapy for nifedipine-induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18--glycyrrhetinic acid (18-GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from patients who presented with nifedipine-induced gingival overgrowth. Experimental ApproachGingival fibroblasts were cultured in medium containing 1% FBS with/without 10M 18-GA for 24 or 48h, and the cell number, cell cycle phase distribution, relative DNA content, apoptotic cell number and morphological characteristics of the cells undergoing apoptosis were measured together with the levels of proteins that regulate these processes and the level of caspase activity. Key Results18-GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G(1) and G(0)/G(1) phases of the cell cycle and the number of apoptotic cells. Nuclear condensation and fragmentation of cells into small apoptotic bodies appeared in the fibroblasts treated with 18-GA. In addition, 18-GA significantly decreased the protein levels of cyclins A and D1, CDKs 2 and 6, phosphorylated Rb (ser(780) and ser(807/811)), Bcl-xL and Bcl-2 and increased the protein levels of p27, cytosolic cytochrome c, pro-caspase-3, and cleaved caspase-3 and the activities of caspases 3 and 9. Conclusions and Implications18-GA inhibited gingival fibroblast growth by suppressing the G(1)/S phase transition and inducing apoptosis. In conclusion, 18-GA may be used as a pharmacotherapy for nifedipine-induced gingival overgrowth.