Figure 8. Schematic diagram showing how cis-khellactone from Angelica amurensis can induce three types of PCD (apoptosis, autophagy-mediated cell death, and necrosis/necroptosis).

Cis-khellactone affected cell growth and viability of several different types of cancer cells in a time- and concentration-dependent manner. In vitro experiments showed that cis-khellactone can suppress cell growth and proliferation of cancer cells and inhibit migration at relatively low concentrations (2.5 and 5 μg/ml). Cis-khellactone can also induce three types of programmed cell death (apoptosis, autophagy-mediated cell death, and necrosis/necroptosis) at higher concentrations (10-20 μg/ml). Cis-khellactone induces autophagy, apoptosis, and necrosis/necroptosis in cancer cells in part by increasing ROS levels and decreasing MMP in cancer cells with minimal effects in normal cells. These findings were confirmed by in vivo experiments using xenografts.