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The furano norclerodane diterpenoid disobulbin-D induces apoptosis in normal human liver L-02 cells
Ist Teil von
Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, 2012-09, Vol.64 (6), p.611-618
Ort / Verlag
Munich: Elsevier GmbH
Erscheinungsjahr
2012
Quelle
Access via ScienceDirect (Elsevier)
Beschreibungen/Notizen
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-G1 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.