title: The furano norclerodane diterpenoid disobulbin-D induces apoptosis in normal human liver L-02 cells.
abstract: Disobulbin-D (DBD), a hepatotoxic furano norclerodane diterpenoid, was isolated by bio-guided fractionation from the rhizome of Dioscorea bulbifera L. In working toward elucidating the cellular and molecular mechanisms of DBD toxicity, we treated normal human liver cell line L-02 cells with DBD in vitro and evaluated its toxicity in terms of cell viability, morphologic changes, induction of apoptosis/necrosis, and caspase 3 activity. The viability of L-02 cells was inhibited by DBD in a concentration and time-dependent manner. Apoptosis was supported by the Annexin V and propidium iodide assay, Hoechst 33258 staining, and the occurrence of a sub-G(1) peak. DBD can cause an increase in caspase 3 activity, and pretreatment with Ac-DEVD-CHO blocked cell death and attenuated the apoptosis, showing that DBD-induced L-02 cell apoptosis is caspase 3-dependent. These results suggest that the effects of DBD on the growth of normal human liver L-02 cells may be due to its induction of cell apoptosis, which may also explain the toxicity observed in the plants containing furano clerodane diterpenoids.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Ma
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Jinlan
authors.initials: J
authors.lastname: Ruan
authors.forename: Xinqi
authors.initials: X
authors.lastname: Tan
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Cuifen
authors.initials: C
authors.lastname: Wang
authors.forename: Xiao Ming
authors.initials: XM
authors.lastname: Zha
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D027742:Dioscorea; D004224:Diterpenes / Q000737:chemistry / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D027343:Rhizome / Q000737:chemistry / Q000633:toxicity
chemical_list: D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts