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Two tetrahydrofurofurano lignans ( 1 and 2 ), four phenylpropanoids ( 3 ⁻ 6 ), and two alkamides ( 7 and 8 ) were isolated from the EtOAc-soluble fraction of the roots of Asarum sieboldii . The chemical structures of the isolates were identified by analysis of spectroscopic data measurements, and by a comparison of their data with published values. The isolates ( 1 , 2 , 4 ⁻ 8 ) were evaluated for their cytotoxicity against human ovarian cancer cells (A2780 and SKOV3) and immortalized ovarian surface epithelial cells (IOSE80PC) using a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Of the isolates, (-)-asarinin ( 1 ) exhibited the most potent cytotoxicity to both A2780 and SKOV3 cells. A propidium iodide/annexin V-fluorescein isothiocyanate (V-FITC) double staining assay showed that (-)-asarinin ( 1 ) induces apoptotic cell death in ovarian cancer cells. In addition, (-)-asarinin ( 1 ) increased the activation of caspase-3, caspase-8, and caspase-9 in ovarian cancer cells. Pretreatment with caspase inhibitors attenuated the cell death induced by (-)-asarinin ( 1 ). In conclusion, our findings show that (-)-asarinin ( 1 ) from the roots of A. sieboldii may induce caspase-dependent apoptotic cell death in human cancer cells.

(−)-Asarinin from the Roots of Asarum sieboldii Induces Apoptotic Cell Death via Caspase Activation in Human Ovarian Cancer Cells