title: Sucutinirane-diterpene derivatives induce apoptosis via oxidative stress in HL-60 cells.
abstract: Previously, we reported the isolation of cassane-type diterpenes, sucutiniranes A-F, from the seeds of Bowdichia nitida. In this study, a series of sucutinirane derivatives was prepared, and their in vitro toxicity in the HL-60 cell line was evaluated. Then the action mechanism of a representative compound that induces cell death was investigated. Whereas C-6 or C-7 diol esters and ether decreased the activity against the HL-60 cell line, furan-oxidized derivatives 12 and 13 showed improvement or retention of the activity compared with those of the natural products sucutinirane A (11), E (1), and F (2). Treatment with sucutinirane derivative 13 elevated caspase 3/7 activity and also decreased expression of Bcl-2 family proteins, Mcl-1, and Bid. Derivative 13 generated reactive oxygen species in HL-60 cells, whose apoptotic effects were attenuated by the addition of an antioxidant, N-acetyl-L-cysteine. These results suggest that cassane butenolide 13 induces apoptosis in HL-60 via its oxidative effects.
authors: Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo, 142-8501, Japan.
authors: Jun
authors: J
authors: Deguchi
authors: Kaori
authors: K
authors: Horiguchi
authors: Chin Piow
authors: CP
authors: Wong
authors: Takahiro
authors: T
authors: Hosoya
authors: Akane
authors: A
authors: Iihoshi
authors: Toshio
authors: T
authors: Kaneda
authors: Hiroshi
authors: H
authors: Morita
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000633:toxicity*; D018922:HL-60 Cells; D006801:Humans; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004224:Diterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D020169:Caspases