Saikosaponin A-induced cell death of a human hepatoma cell line (HuH-7): the significance of the 'sub-G1 peak' in a DNA histogram.

Saikosaponin A (SSA) induced cell death in the human hepatoma cell line (HuH-7) was investigated. Shortly after exposure to SSA, a DNA histogram showed a 'sub-G1 peak', which was recently reported as suggestive of apoptosis by other researchers. However, the electrophoresis of DNA indicated that such was not the case in the present experiment. The decreased intake of rhodamine 123 and the swelling of mitochondria were remarkable shortly after SSA exposure. These data seem to support the idea that the sub-G1 peak represents necrosis rather than apoptosis. Interestingly, the DNA electrophoresis revealed the smear pattern of small DNA fragments shortly after SSA-exposure, although it did not show the apoptotic ladder pattern. This finding and the appearance of the 'sub-G1 peak' is thought to have been a result of the degradation of the nuclear DNA in the early stages of cell death. Because these findings are different not only from apoptosis, but also from typical necrosis, a distinct mechanism of cell death caused by SSA is suggested.