Apoptosis-inducing activity of a steroidal glycoside from Allium chinense G. Don. bulbs in human small-cell lung cancer cells via mitochondrial dysfunction and ER stress.

A saponin fraction from Allium chinense G. Don. bulbs has previously been reported to exhibit cytotoxicity against melanoma and carcinoma cell lines; however, the active compounds responsible for this cytotoxicity have not been identified. A phytochemical investigation was conducted on A. chinense bulbs to identify novel anticancer seeds from natural products. Seven steroidal glycosides (1-7), comprising three spirostan-type (1-3) and four furostan-type (4-7), were obtained. This is the first report of the isolation of 6 and 7 from A. chinese. The cytotoxicity of 1-7 was evaluated in SBC-3 human small-cell lung cancer cells using the MTT assay. Compounds 2, 3, and 5 demonstrated moderate cytotoxicity against SBC-3 cells, with IC values ranging from 15 to 42 μM dose-dependently. Compound 3, (25R)-3β-[(O-α-L-arabinopyranosyl-(1 → 6)-O-[β-D-xylopyranosyl-(1 → 4)]-β-D-glucopyranosyl)oxy]-5α-spirostan-6-one, which exhibited the most potent cytotoxicity among the isolated compounds, induced caspase-dependent apoptotic cell death via both mitochondrial dysfunction leading to reactive oxygen species (ROS) release and endoplasmic reticulum stress caused by ROS. Furthermore, since calreticulin exposure on the outer leaflet of the plasma membrane and extracellular ATP release were observed in SBC-3 cells treated with 3, it may elicit immunogenic cell death in SBC-3 cells.