title: Apoptosis-inducing activity of clofazimine in macrophages.
abstract: Clofazimine is a riminophenazine compound which has been used for the treatment of leprosy since the 1960s. Although the drug is effective in the management of leprosy reactions because of its anti-inflammatory activity, the mechanism leading to the cessation of inflammation is not well understood. In the present study, it was shown that clofazimine exhibits apoptosis-inducing activity in macrophages. When human monocyte-derived macrophages were cultured in vitro in the presence of clofazimine, the cells exhibited a marked decrease in metabolic activity and showed shrinkage in cell size, indicating cell death. Nuclear condensation and fragmentation were also observed by Giemsa and Hoechst 33248 stains. The endonuclease inhibitor ZnCl(2) inhibited the clofazimine-induced cell death. Significant enhancement of caspase-3 activity was observed in clofazimine-treated macrophages and THP-1 cells. Collectively, these results suggest the apoptosis-inducing activity of clofazimine in macrophages, which may also be responsible for the antibacterial properties of clofazimine.
authors.affiliation: Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1, Aoba-cho, Higashimurayama-shi, Tokyo 189-0002, Japan. fukutomi@nih.go.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Fukutomi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Makino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002991:Clofazimine / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D009167:Mycobacterium lepraemurium / Q000187:drug effects
chemical_list: D002991:Clofazimine; D053148:Caspase 3