title: Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth.
abstract: OBJECTIVE
  This 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-α-glycyrrhetinic acid (18α-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.
  
  
  METHODS
  Gingival fibroblasts were cultured in medium containing 1% FBS with/without 10 μM 18α-GA for 24 or 48 h, 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.
  
  
  RESULTS
  18α-GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G1 and G0 /G1 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 18α-GA. In addition, 18α-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
  18α-GA inhibited gingival fibroblast growth by suppressing the G1 /S phase transition and inducing apoptosis. In conclusion, 18α-GA may be used as a pharmacotherapy for nifedipine-induced gingival overgrowth.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Takeuchi
authors.affiliation: Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hiratsuka
authors.affiliation: Department of Preventive and Public Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Arikawa
authors.affiliation: Department of Oral Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Oral Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Komiya
authors.affiliation: Department of Oral Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Akimoto
authors.affiliation: Nihon University, Chiyoda, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Fujii
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology*; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000188:drug therapy; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects
chemical_list: D002121:Calcium Channel Blockers; C119129:18alpha-glycyrrhetinic acid; D004247:DNA; D009543:Nifedipine; D006034:Glycyrrhetinic Acid