Significantly greater antioxidant anticancer activities of 2,3-dehydrosilybin than silybin.
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 IC50 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 H2O2-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 microM markedly inhibited MMP-2,-9 releases as well as invasiveness, while silybin at 90 microM had marginal effects. DHS but not silybin at 30 microM induced apoptosis and loss of mitochondrial membrane potentials. LD50 of DHS was five-fold lower than that of silybin. Our data suggest that DHS may be more useful therapeutically than silybin.
Huber
Axel
A
Department of Internal Medicine IV, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
Thongphasuk
Piyanut
P
Erben
Gerhard
G
Lehmann
Wolf-Dieter
WD
Tuma
Sabine
S
Stremmel
Wolfgang
W
Chamulitrat
Walee
W
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D012838:Silymarin; D000077385:Silybin; D005688:Galactosamine; D006861:Hydrogen Peroxide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9