Significantly greater antioxidant anticancer activities of 2,3-dehydrosilybin than silybin.

Abstract Silybin or silymarin extract has been used to treat liver diseases, and has now been entered into clinical trials for cancer treatment. Here, we compared antioxidant and anticancer activities between silybin and its oxidized form 2,3-dehydrosilybin (DHS). With IC 50 at three-fold lower concentrations than silybin, DHS inhibited reactive oxygen species generation in glucose–glucose oxidase system and HepG2 cells. Compared with silybin, DHS elicited greater protection against H 2 O 2 -induced HepG2 cell death and galactosamine-induced liver injury in vivo . It is known that oxidants induce releases of metalloproteinases (MMP)-2,-9 which are responsible for invasive and metastasis potentials of transformed cells. DHS at 10 μM markedly inhibited MMP-2,-9 releases as well as invasiveness, while silybin at 90 μM had marginal effects. DHS but not silybin at 30 μM induced apoptosis and loss of mitochondrial membrane potentials. LD 50 of DHS was five-fold lower than that of silybin. Our data suggest that DHS may be more useful therapeutically than silybin.